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The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review)

  • Authors:
    • Feifan He
    • Qiuchen Zhang
    • Yunjie Chen
    • Suli Ge
    • Yidai Xie
    • Ruihong Sun
    • Yuqing Wu
    • Jian Xu
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, The Second School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China, The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
    Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 123
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    Published online on: June 11, 2025
       https://doi.org/10.3892/ijmm.2025.5564
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Abstract

Cyclin‑dependent kinase (CDK)4/6 inhibitors regulate the cell cycle by binding to CDK4/6, thus exerting an inhibitory effect, and they have a notable impact on tumor immunity. CDK4/6 inhibitors have been demonstrated to modulate the immune microenvironment by affecting immune cells and immune escape phenomena in the tumor microenvironment. T cells, natural killer cells and macrophages are all regulated by CDK4/6 inhibitors, thereby acting on cancer cells. In addition, these inhibitors modulate immune checkpoints, enhancing antitumor immune responses when combined with immune checkpoint inhibitors, such as programmed death‑ligand 1 and programmed death‑1. However, these inhibitors are not without limitations, as they can enhance tumor immune evasion. Therefore, combination therapies to improve efficacy are being investigated, including immunotherapy, targeted therapy, chemotherapy and radiation therapy. In addition, challenges associated with the widespread use of CDK4/6 inhibitors, such as the emergence of tumor resistance, underscore the necessity for further research to enhance the clinical applicability of these inhibitors.
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1 

Xu H, Yu S, Liu Q, Yuan X, Mani S, Pestell RG and Wu K: Recent advances of highly selective CDK4/6 inhibitors in breast cancer. J Hematol Oncol. 10:972017. View Article : Google Scholar : PubMed/NCBI

2 

Braal CL, Jongbloed EM, Wilting SM, Mathijssen RHJ, Koolen SLW and Jager A: Inhibiting CDK4/6 in breast cancer with palbociclib, ribociclib, and abemaciclib: Similarities and differences. Drugs. 81:317–331. 2021. View Article : Google Scholar :

3 

CDK4/6 inhibitors induce antitumor immunity. Cancer Discov. 7:10522017. View Article : Google Scholar

4 

Goel S, DeCristo MJ, Watt AC, BrinJones H, Sceneay J, Li BB, Khan N, Ubellacker JM, Xie S, Metzger-Filho O, et al: CDK4/6 inhibition triggers anti-tumor immunity. Nature. 548:471–475. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Kong T, Xue Y, Cencic R, Zhu X, Monast A, Fu Z, Pilon V, Sangwan V, Guiot MC, Foulkes WD, et al: eIF4A inhibitors suppress cell-cycle feedback response and acquired resistance to CDK4/6 inhibition in cancer. Mol Cancer Ther. 18:2158–2170. 2019. View Article : Google Scholar : PubMed/NCBI

6 

Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, et al: The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): A randomised phase 2 study. Lancet Oncol. 16:25–35. 2015. View Article : Google Scholar

7 

Lei ZN, Tian Q, Teng QX, Wurpel JND, Zeng L, Pan Y and Chen ZS: Understanding and targeting resistance mechanisms in cancer. MedComm (2020). 4:e2652023. View Article : Google Scholar : PubMed/NCBI

8 

Verma S, Bartlett CH, Schnell P, DeMichele AM, Loi S, Ro J, Colleoni M, Iwata H, Harbeck N, Cristofanilli M, et al: Palbociclib in combination with fulvestrant in women with hormone receptor-Positive/HER2-Negative advanced metastatic breast cancer: Detailed safety analysis from a multicenter, randomized, Placebo-controlled, phase III study (PALOMA-3). Oncologist. 21:1165–1175. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Yang Y, Luo J, Chen X, Yang Z, Mei X, Ma J, Zhang Z, Guo X and Yu X: CDK4/6 inhibitors: A novel strategy for tumor radiosensitization. J Exp Clin Cancer Res. 39:1882020. View Article : Google Scholar : PubMed/NCBI

10 

Sobhani N, D'Angelo A, Pittacolo M, Roviello G, Miccoli A, Corona SP, Bernocchi O, Generali D and Otto T: Updates on the CDK4/6 inhibitory strategy and combinations in breast cancer. Cells. 8:3212019. View Article : Google Scholar : PubMed/NCBI

11 

Abraham J, Coleman R, Elias A, Holmes FA, Kalinsky K, Kittaneh M, Lower E, Mahtani R, Terry Mamounas E, Pegram M, et al: Use of cyclin-dependent kinase (CDK) 4/6 inhibitors for hormone receptor-positive, human epidermal growth factor receptor 2-negative, metastatic breast cancer: A roundtable discussion by The Breast Cancer Therapy Expert Group (BCTEG). Breast Cancer Res Treat. 171:11–20. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Johnson J, Thijssen B, McDermott U, Garnett M, Wessels LFA and Bernards R: Targeting the RB-E2F pathway in breast cancer. Oncogene. 35:4829–4835. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Fassl A, Geng Y and Sicinski P: CDK4 and CDK6 kinases: From basic science to cancer therapy. Science. 375:eabc14952022. View Article : Google Scholar : PubMed/NCBI

14 

Hallett ST, Pastok MW, Morgan RML, Wittner A, Blundell KLIM, Felletar I, Wedge SR, Prodromou C, Noble MEM, Pearl LH and Endicott JA: Differential regulation of G1 CDK complexes by the Hsp90-Cdc37 chaperone system. Cell Rep. 21:1386–1398. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Kwapisz D: Cyclin-dependent kinase 4/6 inhibitors in breast cancer: Palbociclib, ribociclib, and abemaciclib. Breast Cancer Res Treat. 166:41–54. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Guo L, Qi J, Wang H, Jiang X and Liu Y: Getting under the skin: The role of CDK4/6 in melanomas. Eur J Med Chem. 204:1125312020. View Article : Google Scholar : PubMed/NCBI

17 

Pan Q, Luo P, Hu K, Qiu Y, Liu G, Dai S, Cui B, Yin D and Shi C: Periodic changes of cyclin D1 mRNA stability are regulated by PC4 modifications in the cell cycle. J Cell Biol. 223:e2023080662024. View Article : Google Scholar : PubMed/NCBI

18 

O'Leary B, Finn RS and Turner NC: Treating cancer with selective CDK4/6 inhibitors. Nat Rev Clin Oncol. 13:417–430. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Cai Z, Shi Q, Li Y, Jin L, Li S, Wong LL, Wang J, Jiang X, Zhu M, Lin J, et al: LncRNA EILA promotes CDK4/6 inhibitor resistance in breast cancer by stabilizing cyclin E1 protein. Sci Adv. 9:eadi38212023. View Article : Google Scholar : PubMed/NCBI

20 

Beleut M, Rajaram RD, Caikovski M, Ayyanan A, Germano D, Choi Y, Schneider P and Brisken C: Two distinct mechanisms underlie progesterone-induced proliferation in the mammary gland. Proc Natl Acad Sci USA. 107:2989–2994. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Błaszczak-Świątkiewicz K: New selective progesterone receptor modulators and their impact on the RANK/RANKL complex activity. Molecules. 25:13212020. View Article : Google Scholar : PubMed/NCBI

22 

Mauro L, Pellegrino M, Giordano F, Ricchio E, Rizza P, De Amicis F, Catalano S, Bonofiglio D, Panno ML and Andò S: Estrogen receptor-α drives adiponectin effects on cyclin D1 expression in breast cancer cells. FASEB J. 29:2150–2160. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Yang C, Chen L, Li C, Lynch MC, Brisken C and Schmidt EV: Cyclin D1 enhances the response to estrogen and progesterone by regulating progesterone receptor expression. Mol Cell Biol. 30:3111–3125. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Herrera-Abreu MT, Palafox M, Asghar U, Rivas MA, Cutts RJ, Garcia-Murillas I, Pearson A, Guzman M, Rodriguez O, Grueso J, et al: Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor-positive breast cancer. Cancer Res. 76:2301–2313. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Huang X, You L, Nepovimova E, Psotka M, Malinak D, Valko M, Sivak L, Korabecny J, Heger Z, Adam V, et al: Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK). J Enzyme Inhib Med Chem. 38:22372092023. View Article : Google Scholar : PubMed/NCBI

26 

Presti D and Quaquarini E: The PI3K/AKT/mTOR and CDK4/6 pathways in endocrine resistant HR+/HER2-metastatic breast cancer: Biological mechanisms and new treatments. Cancers (Basel). 11:12422019. View Article : Google Scholar

27 

Hao C, Wei Y, Meng W, Zhang J and Yang X: PI3K/AKT/mTOR inhibitors for hormone receptor-positive advanced breast cancer. Cancer Treat Rev. 132:1028612025. View Article : Google Scholar

28 

Liu Q, Liu Y, Li X, Wang D, Zhang A, Pang J, He J, Chen X and Tang NJ: Perfluoroalkyl substances promote breast cancer progression via ERα and GPER mediated PI3K/Akt and MAPK/Erk signaling pathways. Ecotoxicol Environ Saf. 258:1149802023. View Article : Google Scholar

29 

Luboff AJ and DeRemer DL: Capivasertib: A novel AKT inhibitor approved for hormone-receptor-positive, HER-2-negative metastatic breast cancer. Ann Pharmacother. 58:1229–1237. 2024. View Article : Google Scholar : PubMed/NCBI

30 

Michaloglou C, Crafter C, Siersbaek R, Delpuech O, Curwen JO, Carnevalli LS, Staniszewska AD, Polanska UM, Cheraghchi-Bashi A, Lawson M, et al: Combined inhibition of mTOR and CDK4/6 is required for optimal blockade of E2F function and long-term growth inhibition in estrogen receptor-positive breast cancer. Mol Cancer Ther. 17:908–920. 2018. View Article : Google Scholar : PubMed/NCBI

31 

Teh JLF and Aplin AE: Arrested developments: CDK4/6 inhibitor resistance and alterations in the tumor immune microenvironment. Clin Cancer Res. 25:921–927. 2019. View Article : Google Scholar :

32 

Deng J, Wang ES, Jenkins RW, Li S, Dries R, Yates K, Chhabra S, Huang W, Liu H, Aref AR, et al: CDK4/6 inhibition augments antitumor immunity by enhancing T-cell activation. Cancer Discov. 8:216–233. 2018. View Article : Google Scholar

33 

Mognol GP, Carneiro FRG, Robbs BK, Faget DV and Viola JPB: Cell cycle and apoptosis regulation by NFAT transcription factors: New roles for an old player. Cell Death Dis. 7:e21992016. View Article : Google Scholar : PubMed/NCBI

34 

Liu J, Cheng M, Xu J, Liang Y, Yin B and Liang J: Effect of CDK4/6 inhibitors on tumor immune microenvironment. Immunol Invest. 53:437–449. 2024. View Article : Google Scholar : PubMed/NCBI

35 

Scirocchi F, Scagnoli S, Botticelli A, Di Filippo A, Napoletano C, Zizzari IG, Strigari L, Tomao S, Cortesi E, Rughetti A, et al: Immune effects of CDK4/6 inhibitors in patients with HR+/HER2-metastatic breast cancer: Relief from immunosuppression is associated with clinical response. EBioMedicine. 79:1040102022. View Article : Google Scholar

36 

Kent LN and Leone G: The broken cycle: E2F dysfunction in cancer. Nat Rev Cancer. 19:326–338. 2019. View Article : Google Scholar : PubMed/NCBI

37 

Kohlmeyer JL, Lingo JJ, Kaemmer CA, Scherer A, Warrier A, Voigt E, Raygoza Garay JA, McGivney GR, Brockman QR, Tang A, et al: CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression. Clin Cancer Res. 29:3484–3497. 2023. View Article : Google Scholar : PubMed/NCBI

38 

Ruscetti M, Leibold J, Bott MJ, Fennell M, Kulick A, Salgado NR, Chen CC, Ho YJ, Sanchez-Rivera FJ, Feucht J, et al: NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination. Science. 362:1416–1422. 2018. View Article : Google Scholar : PubMed/NCBI

39 

Llanos S, Megias D, Blanco-Aparicio C, Hernández-Encinas E, Rovira M, Pietrocola F and Serrano M: Lysosomal trapping of palbociclib and its functional implications. Oncogene. 38:3886–3902. 2019. View Article : Google Scholar : PubMed/NCBI

40 

De Buck M, Gouwy M, Wang JM, Van Snick J, Opdenakker G, Struyf S and Van Damme J: Structure and expression of different serum amyloid A (SAA) variants and their concentration-dependent functions during host insults. Curr Med Chem. 23:1725–1755. 2016. View Article : Google Scholar : PubMed/NCBI

41 

Sagiv A, Biran A, Yon M, Simon J, Lowe SW and Krizhanovsky V: Granule exocytosis mediates immune surveillance of senescent cells. Oncogene. 32:1971–1977. 2013. View Article : Google Scholar :

42 

Ritschka B, Storer M, Mas A, Heinzmann F, Ortells MC, Morton JP, Sansom OJ, Zender L and Keyes WM: The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes Dev. 31:172–183. 2017. View Article : Google Scholar : PubMed/NCBI

43 

Muñoz-Espín D and Serrano M: Cellular senescence: From physiology to pathology. Nat Rev Mol Cell Biol. 15:482–496. 2014. View Article : Google Scholar : PubMed/NCBI

44 

Favaretto G, Rossi MN, Cuollo L, Laffranchi M, Cervelli M, Soriani A, Sozzani S, Santoni A and Antonangeli F: Neutrophil-activating secretome characterizes palbociclib-induced senescence of breast cancer cells. Cancer Immunol Immunother. 73:1132024. View Article : Google Scholar : PubMed/NCBI

45 

Mehta AK, Cheney EM, Hartl CA, Pantelidou C, Oliwa M, Castrillon JA, Lin JR, Hurst KE, de Oliveira Taveira M, Johnson NT, et al: Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer. Nat Cancer. 2:66–82. 2021. View Article : Google Scholar : PubMed/NCBI

46 

Gu M, Liu Y, Zheng W, Jing Z, Li X, Guo W, Zhao Z, Yang X, Liu Z, Zhu X and Gao W: Combined targeting of senescent cells and senescent macrophages: A new idea for integrated treatment of lung cancer. Semin Cancer Biol. 106-107:43–57. 2024. View Article : Google Scholar : PubMed/NCBI

47 

Fang Y, Zhang Z, Liu Y, Gao T, Liang S, Chu Q, Guan L, Mu W, Fu S, Yang H, et al: Artificial assembled macrophage Co-deliver black phosphorus quantum dot and CDK4/6 inhibitor for colorectal cancer triple-therapy. ACS Appl Mater Interfaces. 14:20628–20640. 2022. View Article : Google Scholar : PubMed/NCBI

48 

Kumar A, Ramani V, Bharti V, de Lima Bellan D, Saleh N, Uzhachenko R, Shen C, Arteaga C, Richmond A, Reddy SM and Vilgelm A: Dendritic cell therapy augments antitumor immunity triggered by CDK4/6 inhibition and immune checkpoint blockade by unleashing systemic CD4 T-cell responses. J Immunother Cancer. 11:e0060192023. View Article : Google Scholar : PubMed/NCBI

49 

Zhang J, Bu X, Wang H, Zhu Y, Geng Y, Nihira NT, Tan Y, Ci Y, Wu F, Dai X, et al: Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature. 553:91–95. 2018. View Article : Google Scholar

50 

Filippone A, Lanza M, Mannino D, Raciti G, Colarossi C, Sciacca D, Cuzzocrea S and Paterniti I: PD1/PD-L1 immune checkpoint as a potential target for preventing brain tumor progression. Cancer Immunol Immunother. 71:2067–2075. 2022. View Article : Google Scholar : PubMed/NCBI

51 

Hossain MA, Liu G, Dai B, Si Y, Yang Q, Wazir J, Birnbaumer L and Yang Y: Reinvigorating exhausted CD8+ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy. Med Res Rev. 41:156–201. 2021. View Article : Google Scholar

52 

Szeto C, Lobos CA, Nguyen AT and Gras S: TCR recognition of peptide-MHC-I: Rule makers and breakers. Int J Mol Sci. 22:682020. View Article : Google Scholar : PubMed/NCBI

53 

Wu X, Gu Z, Chen Y, Chen B, Chen W, Weng L and Liu X: Application of PD-1 blockade in cancer immunotherapy. Comput Struct Biotechnol J. 17:661–674. 2019. View Article : Google Scholar : PubMed/NCBI

54 

Wu M, Huang Q, Xie Y, Wu X, Ma H, Zhang Y and Xia Y: Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation. J Hematol Oncol. 15:242022. View Article : Google Scholar : PubMed/NCBI

55 

Seto T, Sam D and Pan M: Mechanisms of primary and secondary resistance to immune checkpoint inhibitors in cancer. Med Sci (Basel). 7:142019.PubMed/NCBI

56 

Schaer DA, Beckmann RP, Dempsey JA, Huber L, Forest A, Amaladas N, Li Y, Wang YC, Rasmussen ER, Chin D, et al: The CDK4/6 inhibitor abemaciclib induces a T cell inflamed tumor microenvironment and enhances the efficacy of PD-L1 checkpoint blockade. Cell Rep. 22:2978–2994. 2018. View Article : Google Scholar : PubMed/NCBI

57 

Shrestha M, Wang DY, Ben-David Y and Zacksenhaus E: CDK4/6 inhibitors and the pRB-E2F1 axis suppress PVR and PD-L1 expression in triple-negative breast cancer. Oncogenesis. 12:292023. View Article : Google Scholar : PubMed/NCBI

58 

Beaver JA, Amiri-Kordestani L, Charlab R, Chen W, Palmby T, Tilley A, Zirkelbach JF, Yu J, Liu Q, Zhao L, et al: FDA Approval: Palbociclib for the treatment of postmenopausal patients with estrogen Receptor-positive, HER2-Negative metastatic breast cancer. Clin Cancer Res. 21:4760–4766. 2015. View Article : Google Scholar : PubMed/NCBI

59 

Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, et al: Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 375:1925–1936. 2016. View Article : Google Scholar : PubMed/NCBI

60 

Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, et al: Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): Final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 17:425–439. 2016. View Article : Google Scholar : PubMed/NCBI

61 

Wedam S, Fashoyin-Aje L, Bloomquist E, Tang S, Sridhara R, Goldberg KB, Theoret MR, Amiri-Kordestani L, Pazdur R and Beaver JA: FDA approval summary: Palbociclib for male patients with metastatic breast cancer. Clin Cancer Res. 26:1208–1212. 2020. View Article : Google Scholar

62 

Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, Ginther C, Atefi M, Chen I, Fowst C, et al: PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 11:R772009. View Article : Google Scholar : PubMed/NCBI

63 

Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martín M, et al: Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med. 382:514–524. 2020. View Article : Google Scholar

64 

Im SA, Lu YS, Bardia A, Harbeck N, Colleoni M, Franke F, Chow L, Sohn J, Lee KS, Campos-Gomez S, et al: Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 381:307–316. 2019. View Article : Google Scholar : PubMed/NCBI

65 

Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, André F, Winer EP, et al: Ribociclib as First-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 375:1738–1748. 2016. View Article : Google Scholar : PubMed/NCBI

66 

Research C for DE and: FDA expands ribociclib indication in HR-positive, HER2-negative advanced or metastatic breast cancer. FDA. 2024.

67 

Hortobagyi GN, Lacko A, Sohn J, Cruz F, Ruiz Borrego M, Manikhas A, Hee Park Y, Stroyakovskiy D, Yardley DA, Huang CS, et al: A phase III trial of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR-positive/HER2-negative early breast cancer: Final invasive disease-free survival results from the NATALEE trial. Ann Oncol. 36:149–157. 2025. View Article : Google Scholar

68 

Sledge GW, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, et al: MONARCH 2: Abemaciclib in combination with fulvestrant in women With HR+/HER2-Advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 35:2875–2884. 2017. View Article : Google Scholar : PubMed/NCBI

69 

Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, et al: MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 35:3638–3646. 2017. View Article : Google Scholar : PubMed/NCBI

70 

Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, Wildiers H, Hudis CA, O'Shaughnessy J, Zamora E, et al: MONARCH 1, A Phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2-Metastatic breast cancer. Clin Cancer Res. 23:5218–5224. 2017. View Article : Google Scholar : PubMed/NCBI

71 

Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, Zhang QY, Martinez Rodriguez JL, Campone M, Hamilton E, et al: Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, Node-positive, High-risk, early breast cancer (monarchE). J Clin Oncol. 38:3987–3998. 2020. View Article : Google Scholar : PubMed/NCBI

72 

Harbeck N, Rastogi P, Martin M, Tolaney SM, Shao ZM, Fasching PA, Huang CS, Jaliffe GG, Tryakin A, Goetz MP, et al: Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 32:1571–1581. 2021. View Article : Google Scholar : PubMed/NCBI

73 

Royce M, Mulkey F, Osgood C, Bloomquist E and Amiri-Kordestani L: US food and drug administration expanded adjuvant indication of abemaciclib in High-risk early breast cancer. J Clin Oncol. 41:3456–3457. 2023. View Article : Google Scholar : PubMed/NCBI

74 

Sledge GW, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, et al: The effect of abemaciclib plus fulvestrant on overall survival in hormone Receptor-positive, ERBB2-Negative breast cancer that progressed on endocrine Therapy-MONARCH 2: A randomized clinical trial. JAMA Oncol. 6:116–124. 2020. View Article : Google Scholar

75 

Turner NC, Slamon DJ, Ro J, Bondarenko I, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, et al: Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med. 379:1926–1936. 2018. View Article : Google Scholar : PubMed/NCBI

76 

Desnoyers A, Nadler MB, Kumar V, Saleh R and Amir E: Comparison of treatment-related adverse events of different Cyclin-dependent kinase 4/6 inhibitors in metastatic breast cancer: A network meta-analysis. Cancer Treat Rev. 90:1020862020. View Article : Google Scholar : PubMed/NCBI

77 

Kappel C, Elliott MJ, Kumar V, Nadler MB, Desnoyers A and Amir E: Comparative overall survival of CDK4/6 inhibitors in combination with endocrine therapy in advanced breast cancer. Sci Rep. 14:31292024. View Article : Google Scholar : PubMed/NCBI

78 

Slamon D, Lipatov O, Nowecki Z, McAndrew N, Kukielka-Budny B, Stroyakovskiy D, Yardley DA, Huang CS, Fasching PA, Crown J, et al: Ribociclib plus endocrine therapy in early breast cancer. N Engl J Med. 390:1080–1091. 2024. View Article : Google Scholar : PubMed/NCBI

79 

Johnston S, Martin M, Di Leo A, Im SA, Awada A, Forrester T, Frenzel M, Hardebeck MC, Cox J, Barriga S, et al: MONARCH 3 final PFS: A randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer. 5:52019. View Article : Google Scholar : PubMed/NCBI

80 

Carlino L, Christodoulou MS, Restelli V, Caporuscio F, Foschi F, Semrau MS, Costanzi E, Tinivella A, Pinzi L, Lo Presti L, et al: Structure-activity relationships of hexahydrocyclopenta[c]quinoline derivatives as allosteric inhibitors of CDK2 and EGFR. ChemMedChem. 13:2627–2634. 2018. View Article : Google Scholar : PubMed/NCBI

81 

Bisi JE, Sorrentino JA, Jordan JL, Darr DD, Roberts PJ, Tavares FX and Strum JC: Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumors. Oncotarget. 8:42343–42358. 2017. View Article : Google Scholar : PubMed/NCBI

82 

Profitós-Pelejà N, Ribeiro ML, Parra J, Fernández-Serrano M, Marin-Escudero P, Makovski-Silverstein A, Cosenza S, Esteller M and Roué G: Prolonged cell cycle arrest by the CDK4/6 antagonist narazaciclib restores ibrutinib response in preclinical models of BTKi-resistant mantle cell lymphoma. Hematological Oncol. 41:553–554. 2023. View Article : Google Scholar

83 

Freeman-Cook KD, Hoffman RL, Behenna DC, Boras B, Carelli J, Diehl W, Ferre RA, He YA, Hui A, Huang B, et al: Discovery of PF-06873600, a CDK2/4/6 inhibitor for the treatment of cancer. J Med Chem. 64:9056–9077. 2021. View Article : Google Scholar : PubMed/NCBI

84 

Liu C, Liu B, Xu C, Zhang P and Yu C: ETH-155008, a novel selective dual inhibitor of FLT3 and CDK4/6 in preclinical treatment of acute myeloid leukemia. Blood. 134:5141. 2019. View Article : Google Scholar

85 

Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, et al: Preclinical characterization of the CDK4/6 inhibitor LY2835219: In-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 32:825–837. 2014. View Article : Google Scholar : PubMed/NCBI

86 

Goel S, Tan AR, Rugo HS, Aftimos P, Andrić Z, Beelen A, Zhang J, Yi JS, Malik R and O'Shaughnessy J: Trilaciclib prior to gemcitabine plus carboplatin for metastatic triple-negative breast cancer: Phase III PRESERVE 2. Future Oncol. 18:3701–3711. 2022. View Article : Google Scholar : PubMed/NCBI

87 

Lenz HJ, Liu T, Chen EY, Horváth Z, Bondarenko I, Danielewicz I, Ghidini M, García-Alfonso P, Jones R, Aapro M, et al: Trilaciclib prior to FOLFOXIRI/bevacizumab for patients with untreated metastatic colorectal cancer: Phase 3 PRESERVE 1 trial. JNCI Cancer Spectr. 9:pkae1162025. View Article : Google Scholar :

88 

Zhang J, Yang N, Ji D, Shen W, Li W, Han R, Wang N, Tao H, Chapman SC, Sykes AK, et al: A Randomized phase i study of abemaciclib in chinese patients with Advanced and/or metastatic cancers. Target Oncol. 16:177–187. 2021. View Article : Google Scholar : PubMed/NCBI

89 

DeWire M, Fuller C, Hummel TR, Chow LML, Salloum R, de Blank P, Pater L, Lawson S, Zhu X, Dexheimer P, et al: A phase I/II study of ribociclib following radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). J Neurooncol. 149:511–522. 2020. View Article : Google Scholar : PubMed/NCBI

90 

Hart LL, Ferrarotto R, Andric ZG, Beck JT, Subramanian J, Radosavljevic DZ, Zaric B, Hanna WT, Aljumaily R, Owonikoko TK, et al: Myelopreservation with trilaciclib in patients receiving topotecan for small cell lung cancer: Results from a randomized, double-blind, placebo-controlled phase II study. Adv Ther. 38:350–365. 2021. View Article : Google Scholar :

91 

Xu B, Li H, Zhang Q, Sun W, Yu Y, Li W, Wang S, Liao N, Shen P, Liu Y, et al: Pharmacokinetics, safety, activity, and biomarker analysis of palbociclib plus letrozole as first-line treatment for ER+/HER2-advanced breast cancer in Chinese women. Cancer Chemother Pharmacol. 88:131–141. 2021. View Article : Google Scholar : PubMed/NCBI

92 

Miller TW, Traphagen NA, Li J, Lewis LD, Lopes B, Asthagiri A, Loomba J, De Jong J, Schiff D, Patel SH, et al: Tumor pharmacokinetics and pharmacodynamics of the CDK4/6 inhibitor ribociclib in patients with recurrent glioblastoma. J Neurooncol. 144:563–572. 2019. View Article : Google Scholar : PubMed/NCBI

93 

Wander SA, Cohen O, Gong X, Johnson GN, Buendia-Buendia JE, Lloyd MR, Kim D, Luo F, Mao P, Helvie K, et al: The genomic landscape of intrinsic and acquired resistance to Cyclin-dependent kinase 4/6 inhibitors in patients with hormone Receptor-positive metastatic breast cancer. Cancer Discov. 10:1174–1193. 2020. View Article : Google Scholar : PubMed/NCBI

94 

Kim S, Leong A, Kim M and Yang HW: CDK4/6 initiates Rb inactivation and CDK2 activity coordinates cell-cycle commitment and G1/S transition. Sci Rep. 12:168102022. View Article : Google Scholar : PubMed/NCBI

95 

Fisher RP: Getting to S: CDK functions and targets on the path to cell-cycle commitment. F1000Res. 5:23742016. View Article : Google Scholar : PubMed/NCBI

96 

Kim S, Armand J, Safonov A, Zhang M, Soni RK, Schwartz G, McGuinness JE, Hibshoosh H, Razavi P, Kim M, et al: Sequential activation of E2F via Rb degradation and c-Myc drives resistance to CDK4/6 inhibitors in breast cancer. Cell Rep. 42:1131982023. View Article : Google Scholar : PubMed/NCBI

97 

O'Leary B, Cutts RJ, Liu Y, Hrebien S, Huang X, Fenwick K, André F, Loibl S, Loi S, Garcia-Murillas I, et al: The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 trial. Cancer Discov. 8:1390–1403. 2018. View Article : Google Scholar : PubMed/NCBI

98 

Sharma A, Comstock CES, Knudsen ES, Cao KH, Hess-Wilson JK, Morey LM, Barrera J and Knudsen KE: Retinoblastoma tumor suppressor status is a critical determinant of therapeutic response in prostate cancer cells. Cancer Res. 67:6192–6203. 2007. View Article : Google Scholar : PubMed/NCBI

99 

Malumbres M, Sotillo R, Santamaría D, Galán J, Cerezo A, Ortega S, Dubus P and Barbacid M: Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6. Cell. 118:493–504. 2004. View Article : Google Scholar : PubMed/NCBI

100 

Pandey K, An HJ, Kim SK, Lee SA, Kim S, Lim SM, Kim GM, Sohn J and Moon YW: Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review. Int J Cancer. 145:1179–1188. 2019. View Article : Google Scholar :

101 

Goel S, Bergholz JS and Zhao JJ: Targeting CDK4 and CDK6 in cancer. Nat Rev Cancer. 22:356–372. 2022. View Article : Google Scholar : PubMed/NCBI

102 

Cen L, Carlson BL, Schroeder MA, Ostrem JL, Kitange GJ, Mladek AC, Fink SR, Decker PA, Wu W, Kim JS, et al: p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells. Neuro Oncol. 14:870–881. 2012. View Article : Google Scholar : PubMed/NCBI

103 

Iwata S, Tatsumi Y, Yonemoto T, Araki A, Itami M, Kamoda H, Tsukanishi T, Hagiwara Y, Kinoshita H, Ishii T, et al: CDK4 overexpression is a predictive biomarker for resistance to conventional chemotherapy in patients with osteosarcoma. Oncol Rep. 46:1352021. View Article : Google Scholar : PubMed/NCBI

104 

Schachter MM, Merrick KA, Larochelle S, Hirschi A, Zhang C, Shokat KM, Rubin SM and Fisher RP: A Cdk7-Cdk4 T-loop phosphorylation cascade promotes G1 progression. Mol Cell. 50:250–260. 2013. View Article : Google Scholar : PubMed/NCBI

105 

Coombes RC, Howell S, Lord SR, Kenny L, Mansi J, Mitri Z, Palmieri C, Chap LI, Richards P, Gradishar W, et al: Dose escalation and expansion cohorts in patients with advanced breast cancer in a Phase I study of the CDK7-inhibitor samuraciclib. Nat Commun. 14:44442023. View Article : Google Scholar : PubMed/NCBI

106 

Yang C, Li Z, Bhatt T, Dickler M, Giri D, Scaltriti M, Baselga J, Rosen N and Chandarlapaty S: Acquired CDK6 amplification promotes breast cancer resistance to CDK4/6 inhibitors and loss of ER signaling and dependence. Oncogene. 36:2255–2264. 2017. View Article : Google Scholar :

107 

Schoninger SF and Blain SW: The ongoing search for biomarkers of CDK4/6 inhibitor responsiveness in breast cancer. Mol Cancer Ther. 19:3–12. 2020. View Article : Google Scholar : PubMed/NCBI

108 

Li Z, Razavi P, Li Q, Toy W, Liu B, Ping C, Hsieh W, Sanchez-Vega F, Brown DN, Da Cruz Paula AF, et al: Loss of the FAT1 tumor suppressor promotes resistance to CDK4/6 inhibitors via the hippo pathway. Cancer Cell. 34:893–905.e8. 2018. View Article : Google Scholar : PubMed/NCBI

109 

Cornell L, Wander SA, Visal T, Wagle N and Shapiro GI: MicroRNA-mediated suppression of the TGF-β pathway confers transmissible and reversible CDK4/6 inhibitor resistance. Cell Rep. 26:2667–2680.e7. 2019. View Article : Google Scholar

110 

Chu C, Geng Y, Zhou Y and Sicinski P: Cyclin E in normal physiology and disease states. Trends Cell Biol. 31:732–746. 2021. View Article : Google Scholar : PubMed/NCBI

111 

Watt AC and Goel S: Cellular mechanisms underlying response and resistance to CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer. Breast Cancer Res. 24:172022. View Article : Google Scholar : PubMed/NCBI

112 

Chandarlapaty S and Razavi P: Cyclin E mRNA: Assessing Cyclin-dependent kinase (CDK) activation state to elucidate breast cancer resistance to CDK4/6 Inhibitors. J Clin Oncol. 37:1148–1150. 2019. View Article : Google Scholar : PubMed/NCBI

113 

Guarducci C, Bonechi M, Benelli M, Biagioni C, Boccalini G, Romagnoli D, Verardo R, Schiff R, Osborne CK, De Angelis C, et al: Cyclin E1 and Rb modulation as common events at time of resistance to palbociclib in hormone receptor-positive breast cancer. NPJ Breast Cancer. 4:382018. View Article : Google Scholar : PubMed/NCBI

114 

Turner NC, Liu Y, Zhu Z, Loi S, Colleoni M, Loibl S, DeMichele A, Harbeck N, André F, Bayar MA, et al: Cyclin E1 expression and palbociclib efficacy in previously treated hormone Receptor-positive metastatic breast cancer. J Clin Oncol. 37:1169–1178. 2019. View Article : Google Scholar : PubMed/NCBI

115 

Al-Qasem AJ, Alves CL, Ehmsen S, Tuttolomondo M, Terp MG, Johansen LE, Vever H, Hoeg LVA, Elias D, Bak M and Ditzel HJ: Co-targeting CDK2 and CDK4/6 overcomes resistance to aromatase and CDK4/6 inhibitors in ER+ breast cancer. NPJ Precis Oncol. 6:682022. View Article : Google Scholar : PubMed/NCBI

116 

Gong X, Du J, Parsons SH, Merzoug FF, Webster Y, Iversen PW, Chio LC, Van Horn RD, Lin X, Blosser W, et al: Aurora a kinase inhibition is synthetic lethal with loss of the RB1 tumor suppressor gene. Cancer Discov. 9:248–263. 2019. View Article : Google Scholar

117 

Hsueh KW, Fu SL, Chang CB, Chang YL and Lin CH: A novel Aurora-A-mediated phosphorylation of p53 inhibits its interaction with MDM2. Biochim Biophys Acta. 1834:508–515. 2013. View Article : Google Scholar

118 

Turner N and Grose R: Fibroblast growth factor signalling: From development to cancer. Nat Rev Cancer. 10:116–129. 2010. View Article : Google Scholar : PubMed/NCBI

119 

Formisano L, Lu Y, Servetto A, Hanker AB, Jansen VM, Bauer JA, Sudhan DR, Guerrero-Zotano AL, Croessmann S, Guo Y, et al: Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer. Nat Commun. 10:13732019. View Article : Google Scholar : PubMed/NCBI

120 

Courjal F, Cuny M, Simony-Lafontaine J, Louason G, Speiser P, Zeillinger R, Rodriguez C and Theillet C: Mapping of DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: Definition of phenotypic groups. Cancer Res. 57:4360–4367. 1997.PubMed/NCBI

121 

Sharpe R, Pearson A, Herrera-Abreu MT, Johnson D, Mackay A, Welti JC, Natrajan R, Reynolds AR, Reis-Filho JS, Ashworth A and Turner NC: FGFR signaling promotes the growth of triple-negative and basal-like breast cancer cell lines both in vitro and in vivo. Clin Cancer Res. 17:5275–5286. 2011. View Article : Google Scholar : PubMed/NCBI

122 

Mao P, Cohen O, Kowalski KJ, Kusiel JG, Buendia-Buendia JE, Cuoco MS, Exman P, Wander SA, Waks AG, Nayar U, et al: Acquired FGFR and FGF alterations confer resistance to estrogen receptor (ER) targeted therapy in ER+ metastatic breast cancer. Clin Cancer Res. 26:5974–5989. 2020. View Article : Google Scholar : PubMed/NCBI

123 

Turner N, Pearson A, Sharpe R, Lambros M, Geyer F, Lopez-Garcia MA, Natrajan R, Marchio C, Iorns E, Mackay A, et al: FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer. Cancer Res. 70:2085–2094. 2010. View Article : Google Scholar : PubMed/NCBI

124 

Ersahin T, Tuncbag N and Cetin-Atalay R: The PI3K/AKT/mTOR interactive pathway. Mol Biosyst. 11:1946–1954. 2015. View Article : Google Scholar : PubMed/NCBI

125 

Cai Z, Wang J, Li Y, Shi Q, Jin L, Li S, Zhu M, Wang Q, Wong LL, Yang W, et al: Overexpressed Cyclin D1 and CDK4 proteins are responsible for the resistance to CDK4/6 inhibitor in breast cancer that can be reversed by PI3K/mTOR inhibitors. Sci China Life Sci. 66:94–109. 2023. View Article : Google Scholar

126 

Hobbs GA, Wittinghofer A and Der CJ: Selective targeting of the KRAS G12C mutant: Kicking KRAS when it's down. Cancer Cell. 29:251–253. 2016. View Article : Google Scholar : PubMed/NCBI

127 

Luangdilok S, Wanchaijiraboon P, Chantranuwatana P, Teerapakpinyo C, Shuangshoti S and Sriuranpong V: Cyclin D1 expression as a potential prognostic factor in advanced KRAS-mutant non-small cell lung cancer. Transl Lung Cancer Res. 8:959–966. 2019. View Article : Google Scholar

128 

Tran KA, Cheng MY, Mitra A, Ogawa H, Shi VY, Olney LP, Kloxin AM and Maverakis E: MEK inhibitors and their potential in the treatment of advanced melanoma: The advantages of combination therapy. Drug Des Devel Ther. 10:43–52. 2016.PubMed/NCBI

129 

Finn RS, Aleshin A and Slamon DJ: Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers. Breast Cancer Res. 18:172016. View Article : Google Scholar : PubMed/NCBI

130 

Alves CL, Elias D, Lyng M, Bak M, Kirkegaard T, Lykkesfeldt AE and Ditzel HJ: High CDK6 protects cells from Fulvestrant-mediated apoptosis and is a predictor of resistance to fulvestrant in estrogen Receptor-positive metastatic breast cancer. Clin Cancer Res. 22:5514–5526. 2016. View Article : Google Scholar : PubMed/NCBI

131 

Shaulian E and Karin M: AP-1 in cell proliferation and survival. Oncogene. 20:2390–2400. 2001. View Article : Google Scholar : PubMed/NCBI

132 

Shen Q, Uray IP, Li Y, Zhang Y, Hill J, Xu XC, Young MR, Gunther EJ, Hilsenbeck SG, Colburn NH, et al: Targeting the activator protein 1 transcription factor for the prevention of estrogen receptor-negative mammary tumors. Cancer Prev Res (Phila). 1:45–55. 2008. View Article : Google Scholar

133 

Hydbring P, Castell A and Larsson LG: MYC modulation around the CDK2/p27/SKP2 axis. Genes (Basel). 8:1742017. View Article : Google Scholar : PubMed/NCBI

134 

Takahashi M, Tokunaga E, Mori J, Tanizawa Y, van der Walt JS, Kawaguchi T, Goetz MP and Toi M: Japanese subgroup analysis of the phase 3 MONARCH 3 study of abemaciclib as initial therapy for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Breast Cancer. 29:174–184. 2022. View Article : Google Scholar

135 

Hamilton E, Cortes J, Ozyilkan O, Chen SC, Petrakova K, Manikhas A, Jerusalem G, Hegg R, Huober J, Zhang W, et al: nextMONARCH Phase 2 randomized clinical trial: Overall survival analysis of abemaciclib monotherapy or in combination with tamoxifen in patients with endocrine-refractory HR +, HER2-metastatic breast cancer. Breast Cancer Res Treat. 195:55–64. 2022. View Article : Google Scholar : PubMed/NCBI

136 

Goetz MP, Hamilton EP, Campone M, Hurvitz SA, Cortes J, Johnston S, Llombart-Cussac A, Kaufman PA, Toi M, Jerusalem G, et al: Landscape of baseline and acquired genomic alterations in circulating tumor DNA with abemaciclib alone or with endocrine therapy in advanced breast cancer. Clin Cancer Res. 30:2233–2244. 2024. View Article : Google Scholar :

137 

Pandey K, Park N, Park KS, Hur J, Cho YB, Kang M, An HJ, Kim S, Hwang S and Moon YW: Combined CDK2 and CDK4/6 inhibition overcomes palbociclib resistance in breast cancer by enhancing senescence. Cancers (Basel). 12:35662020. View Article : Google Scholar : PubMed/NCBI

138 

Glaviano A, Wander SA, Baird RD, Yap KC, Lam HY, Toi M, Carbone D, Geoerger B, Serra V, Jones RH, et al: Mechanisms of sensitivity and resistance to CDK4/CDK6 inhibitors in hormone receptor-positive breast cancer treatment. Drug Resist Updat. 76:1011032024. View Article : Google Scholar : PubMed/NCBI

139 

Mouron S, Manso L, Caleiras E, Rodríguez-Peralto JL, Rueda OM, Caldas C, Colomer R, Quintela-Fandino M and Bueno MJ: FGFR1 amplification or overexpression and hormonal resistance in luminal breast cancer: Rationale for a triple blockade of ER, CDK4/6, and FGFR1. Breast Cancer Res. 23:212021. View Article : Google Scholar : PubMed/NCBI

140 

Wang N, Ma T and Yu B: Targeting epigenetic regulators to overcome drug resistance in cancers. Signal Transduct Target Ther. 8:692023. View Article : Google Scholar : PubMed/NCBI

141 

Xue Y and Zhai J: Strategy of combining CDK4/6 inhibitors with other therapies and mechanisms of resistance. Int J Clin Exp Pathol. 17:189–207. 2024. View Article : Google Scholar : PubMed/NCBI

142 

Manohar PM and Davidson NE: Updates in endocrine therapy for metastatic breast cancer. Cancer Biol Med. 19:202–212. 2022.

143 

Finn RS, Dieras V, Rugo HS, Joy AA, Moulder SL, Walshe JM, Mukai H, Shparyk YV, Park IH, Mori A, et al: Palbociclib (PAL) + letrozole (L) as first-line (1L) therapy (tx) in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC): Efficacy and safety across patient (pt) subgroups. J Clin Oncol. 35:10392017. View Article : Google Scholar

144 

Kalinsky K, Accordino MK, Chiuzan C, Mundi PS, Trivedi MS, Novik Y, Tiersten A, Raptis G, Baer LN, Oh SY, et al: A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC): MAINTAIN trial. J Clin Oncol. 40:LBA10042022. View Article : Google Scholar

145 

Bidard FC, Kaklamani VG, Neven P, Streich G, Montero AJ, Forget F, Mouret-Reynier MA, Sohn JH, Taylor D, Harnden KK, et al: Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for Estrogen Receptor-positive, human epidermal growth factor receptor 2-Negative advanced breast cancer: Results from the randomized phase III EMERALD Trial. J Clin Oncol. 40:3246–3256. 2022. View Article : Google Scholar : PubMed/NCBI

146 

Oliveira M, Pominchuck D, Nowecki Z, Hamilton E, Kulyaba Y, Andabekov T, Hotko Y, Melkadze T, Nemsadze G, Neven P, et al: Abstract GS3-02: GS3-02 Camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: Results of the randomized, multi-dose Phase 2 SERENA-2 trial. Cancer Res. 83:GS3–02. 2023. View Article : Google Scholar

147 

Research C for DE and: FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. FDA. 2023.

148 

Magge T, Rajendran S, Brufsky AM and Foldi J: CDK4/6 inhibitors: The Devil is in the detail. Curr Oncol Rep. 26:665–678. 2024. View Article : Google Scholar : PubMed/NCBI

149 

Sonke GS, Van Ommen-Nijhof A, Wortelboer N, Noort VVD, Swinkels AC, Blommestein HM, Beeker A, Beelen K, Hamming LC, Heijns JB, et al: Primary outcome analysis of the phase 3 SONIA trial (BOOG 2017-03) on selecting the optimal position of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). J Clin Oncol. 41:LBA10002023. View Article : Google Scholar

150 

Sonke GS, van Ommen-Nijhof A, Wortelboer N, van der Noort V, Swinkels ACP, Blommestein HM, Guerrero Paez C, Mol L, Beeker A, Beelene K, et al: Early versus deferred use of CDK4/6 inhibitors in advanced breast cancer. Nature. 636:474–480. 2024. View Article : Google Scholar : PubMed/NCBI

151 

Ogata R, Kishino E, Saitoh W, Koike Y and Kurebayashi J: Resistance to cyclin-dependent kinase (CDK) 4/6 inhibitors confers cross-resistance to other CDK inhibitors but not to chemotherapeutic agents in breast cancer cells. Breast Cancer. 28:206–215. 2021. View Article : Google Scholar

152 

Rugo HS, Bardia A, Marmé F, Cortés J, Schmid P, Loirat D, Trédan O, Ciruelos E, Dalenc F, Gómez Pardo P, et al: Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): A randomised, open-label, multicentre, phase 3 trial. Lancet. 402:1423–1433. 2023. View Article : Google Scholar : PubMed/NCBI

153 

Cao YN, Zheng LL, Wang D, Liang XX, Gao F and Zhou XL: Recent advances in microtubule-stabilizing agents. Eur J Med Chem. 143:806–828. 2018. View Article : Google Scholar

154 

Cretella D, Fumarola C, Bonelli M, Alfieri R, La Monica S, Digiacomo G, Cavazzoni A, Galetti M, Generali D and Petronini PG: Pre-treatment with the CDK4/6 inhibitor palbociclib improves the efficacy of paclitaxel in TNBC cells. Sci Rep. 9:130142019. View Article : Google Scholar : PubMed/NCBI

155 

Zhang XH, Cheng Y, Shin JY, Kim JO, Oh JE and Kang JH: A CDK4/6 inhibitor enhances cytotoxicity of paclitaxel in lung adenocarcinoma cells harboring mutant KRAS as well as wild-type KRAS. Cancer Biol Ther. 14:597–605. 2013. View Article : Google Scholar : PubMed/NCBI

156 

Kim JY, Jayne LA, Bai Y, Feng MJHH, Clark MA, Chung S, W Christman J, Cianciolo RE and Pabla NS: Ribociclib mitigates cisplatin-associated kidney injury through retinoblastoma-1 dependent mechanisms. Biochem Pharmaco. 177:1139392020. View Article : Google Scholar

157 

Liu M, Cui L, Li X, Xia C, Li Y, Wang R, Ren F, Liu H and Chen J: PD-0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance. Thorac Cancer. 12:924–931. 2021. View Article : Google Scholar : PubMed/NCBI

158 

Ma CX, Gao F, Luo J, Northfelt DW, Goetz M, Forero A, Hoog J, Naughton M, Ademuyiwa F and Suresh R: NeoPalAna: Neoadjuvant palbociclib, a Cyclin-dependent kinase 4/6 inhibitor, and anastrozole for clinical stage 2 or 3 estrogen receptor-positive breast cancer. Clin Cancer Res. 23:4055–4065. 2017. View Article : Google Scholar : PubMed/NCBI

159 

Chow LWC, Morita S, Chow CYC, Ng WK and Toi M: Neoadjuvant palbociclib on ER+ breast cancer (N007): Clinical response and EndoPredict's value. Endocr Relat Cancer. 25:123–130. 2018. View Article : Google Scholar

160 

Prat A, Saura C, Pascual T, Hernando C, Muñoz M, Paré L, González Farré B, Fernández PL, Galván P, Chic N, et al: Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2-negative, luminal B breast cancer (CORALLEEN): An open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 21:33–43. 2020. View Article : Google Scholar

161 

Delaloge S, Dureau S, D'Hondt V, Desmoulins I, Heudel PE, Duhoux FP, Levy C, Lerebours F, Mouret-Reynier MA, Dalenc F, et al: Survival outcomes after neoadjuvant letrozole and palbociclib versus third generation chemotherapy for patients with high-risk oestrogen receptor-positive HER2-negative breast cancer. Eur J Cancer. 166:300–308. 2022. View Article : Google Scholar : PubMed/NCBI

162 

Bonelli M, La Monica S, Fumarola C and Alfieri R: Multiple effects of CDK4/6 inhibition in cancer: From cell cycle arrest to immunomodulation. Biochem Pharmacol. 170:1136762019. View Article : Google Scholar : PubMed/NCBI

163 

Zhang S, Xu Q, Sun W and Zhou J and Zhou J: Immunomodulatory effects of CDK4/6 inhibitors. Biochim Biophys Acta Rev Cancer. 1878:1889122023. View Article : Google Scholar : PubMed/NCBI

164 

De Angelis C, Fu X, Cataldo ML, Nardone A, Pereira R, Veeraraghavan J, Nanda S, Qin L, Sethunath V, Wang T, et al: Activation of the IFN signaling pathway is associated with resistance to CDK4/6 inhibitors and immune checkpoint activation in ER-Positive breast cancer. Clin Cancer Res. 27:4870–4882. 2021. View Article : Google Scholar : PubMed/NCBI

165 

Wang Q, Guldner IH, Golomb SM, Sun L, Harris JA, Lu X and Zhang S: Single-cell profiling guided combinatorial immunotherapy for fast-evolving CDK4/6 inhibitor-resistant HER2-positive breast cancer. Nat Commun. 10:38172019. View Article : Google Scholar : PubMed/NCBI

166 

Wu CC, Wang YA, Livingston JA, Zhang J and Futreal PA: Prediction of biomarkers and therapeutic combinations for anti-PD-1 immunotherapy using the global gene network association. Nat Commun. 13:422022. View Article : Google Scholar : PubMed/NCBI

167 

Jang HJ, Truong CY, Lo EM, Holmes HM, Ramos D, Ramineni M, Lee JS, Wang DY, Pietropaolo M, Ripley RT, et al: Inhibition of cyclin dependent kinase 4/6 overcomes primary resistance to programmed cell death 1 blockade in malignant mesothelioma. Ann Thorac Surg. 114:1842–1852. 2022. View Article : Google Scholar

168 

Litchfield K, Reading JL, Puttick C, Thakkar K, Abbosh C, Bentham R, Watkins TBK, Rosenthal R, Biswas D, Rowan A, et al: Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell. 184:596–614.e14. 2021. View Article : Google Scholar : PubMed/NCBI

169 

Jerby-Arnon L, Shah P, Cuoco MS, Rodman C, Su MJ, Melms JC, Leeson R, Kanodia A, Mei S, Lin JR, et al: A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade. Cell. 175:984–997.e24. 2018. View Article : Google Scholar : PubMed/NCBI

170 

Rugo HS, Kabos P, Beck JT, Jerusalem G, Wildiers H, Sevillano E, Paz-Ares L, Chisamore MJ, Chapman SC, Hossain AM, et al: Abemaciclib in combination with pembrolizumab for HR+, HER2-metastatic breast cancer: Phase 1b study. NPJ Breast Cancer. 8:1182022. View Article : Google Scholar

171 

Yuan Y, Lee JS, Yost SE, Frankel PH, Ruel C, Egelston CA, Guo W, Padam S, Tang A, Martinez N, et al: Phase I/II trial of palbociclib, pembrolizumab and letrozole in patients with hormone receptor-positive metastatic breast cancer. Eur J Cancer. 154:11–20. 2021. View Article : Google Scholar : PubMed/NCBI

172 

Lee EK, Esselen KM, Kolin DL, Lee LJ, Matulonis UA and Konstantinopoulos PA: Combined CDK4/6 and PD-1 inhibition in refractory SMARCA4-deficient Small-cell carcinoma of the ovary, hypercalcemic type. JCO Precis Oncol. 4:736–742. 2020. View Article : Google Scholar : PubMed/NCBI

173 

Xue Y, Meehan B, Fu Z, Wang XQD, Fiset PO, Rieker R, Levins C, Kong T, Zhu X, Morin G, et al: SMARCA4 loss is synthetic lethal with CDK4/6 inhibition in non-small cell lung cancer. Nat Commun. 10:5572019. View Article : Google Scholar : PubMed/NCBI

174 

Bose S, Lee T, Choi S, Fazlollahi L, Rasiej MJ, Schwartz GK and Ingham M: CDK4/6 inhibition with Anti-PD-1 checkpoint blockade induces major response in aggressive classic kaposi sarcoma after previous progression on Anti-PD-1 alone. JCO Precis Oncol. 6:e21005502022. View Article : Google Scholar : PubMed/NCBI

175 

Daniel D, Kuchava V, Bondarenko I, Ivashchuk O, Reddy S, Jaal J, Kudaba I, Hart L, Matitashvili A, Pritchett Y, et al: Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre, randomised, double-blind, placebo-controlled Phase II trial. Int J Cancer. 148:2557–2570. 2021. View Article : Google Scholar :

176 

Mayer EL, Ren Y, Wagle N, Mahtani R, Ma C, DeMichele A, Cristofanilli M, Meisel J, Miller KD, Jolly T, et al: Abstract GS3-06: GS3-06 Palbociclib After CDK4/6i and endocrine therapy (PACE): A randomized phase II study of fulvestrant, palbociclib, and avelumab for endocrine Pre-treated ER+/HER2-metastatic breast cancer. Cancer Res. 83:GS3–06. 2023. View Article : Google Scholar

177 

Jerusalem G, Prat A, Salgado R, Reinisch M, Saura C, Ruiz-Borrego M, Nikolinakos P, Ades F, Filian J, Huang N, et al: Neoadjuvant nivolumab + palbociclib + anastrozole for oestrogen receptor-positive/human epidermal growth factor receptor 2-negative primary breast cancer: Results from CheckMate 7A8. Breast. 72:1035802023. View Article : Google Scholar : PubMed/NCBI

178 

Dennis MJ, Sacco AG, Qi Y, Bykowski J, Pittman E, Chen R, Messer K, Cohen EEW and Gold KA: A phase I study of avelumab, palbociclib, and cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma. Oral Oncol. 135:1062192022. View Article : Google Scholar : PubMed/NCBI

179 

Pujol JL, Vansteenkiste J, Paz-Ares Rodríguez L, Gregorc V, Mazieres J, Awad M, Jänne PA, Chisamore M, Hossain AM, Chen Y and Beck JT: Abemaciclib in combination with pembrolizumab for stage IV KRAS-mutant or squamous NSCLC: A phase 1b study. JTO Clin Res Rep. 2:1002342021.PubMed/NCBI

180 

Patnaik A, Yap TA, Chung HC, de Miguel MJ, Bang YJ, Lin CC, Su WC, Italiano A, Chow KH, Szpurka AM, et al: Safety and clinical activity of a new Anti-PD-L1 antibody as monotherapy or combined with targeted therapy in advanced solid tumors: The PACT Phase Ia/Ib trial. Clin Cancer Res. 27:1267–1277. 2021. View Article : Google Scholar

181 

Garrido-Castro AC and Goel S: CDK4/6 inhibition in breast cancer: Mechanisms of response and treatment failure. Curr Breast Cancer Rep. 9:26–33. 2017. View Article : Google Scholar : PubMed/NCBI

182 

Clark AS, Makhlin I and DeMichele A: Setting the pick: Can PI3K inhibitors circumvent CDK4/6 inhibitor resistance? Clin Cancer Res. 27:371–373. 2021. View Article : Google Scholar

183 

Masuda J, Sakai H, Tsurutani J, Tanabe Y, Masuda N, Iwasa T, Takahashi M, Futamura M, Matsumoto K, Aogi K, et al: Efficacy safety, and biomarker analysis of nivolumab in combination with abemaciclib plus endocrine therapy in patients with HR-positive HER2-negative metastatic breast cancer: A phase II study (WJOG11418B NEWFLAME trial). J Immunother Cancer. 11:e0071262023. View Article : Google Scholar

184 

Bedard PL, Hyman DM, Davids MS and Siu LL: Small molecules, big impact: 20 years of targeted therapy in oncology. Lancet. 395:1078–1088. 2020. View Article : Google Scholar : PubMed/NCBI

185 

Gómez Tejeda Zañudo J, Barroso-Sousa R, Jain E, Jin Q, Li T, Buendia-Buendia JE, Pereslete A, Abravanel DL, Ferreira AR, Wrabel E, et al: Exemestane plus everolimus and palbociclib in metastatic breast cancer: Clinical response and genomic/transcriptomic determinants of resistance in a phase I/II trial. Nat Commun. 15:24462024. View Article : Google Scholar : PubMed/NCBI

186 

Jhaveri KL, Accordino MK, Bedard PL, Cervantes A, Gambardella V, Hamilton E, Italiano A, Kalinsky K, Krop IE, Oliveira M, et al: Phase I/Ib trial of inavolisib plus palbociclib and endocrine therapy for PIK3CA-Mutated, hormone Receptor-positive, human epidermal growth factor Receptor 2-Negative advanced or metastatic breast cancer. J Clin Oncol. 42:3947–3956. 2024. View Article : Google Scholar : PubMed/NCBI

187 

Yardley DA, Noguchi S, Pritchard KI, Burris HA III, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, et al: Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 30:870–884. 2013. View Article : Google Scholar : PubMed/NCBI

188 

Pascual J, Lim JSJ, Macpherson IR, Armstrong AC, Ring A, Okines AFC, Cutts RJ, Herrera-Abreu MT, Garcia-Murillas I, Pearson A, et al: Triplet therapy with palbociclib, taselisib, and fulvestrant in PIK3CA-mutant breast cancer and doublet palbociclib and taselisib in Pathway-mutant solid cancers. Cancer Discov. 11:92–107. 2021. View Article : Google Scholar

189 

Wander SA, Juric D, Supko JG, Micalizzi DS, Spring S, Vidula N, Beeler M, Habin KR, Viscosi E, Fitzgerald DM, et al: Phase Ib trial to evaluate safety and anti-tumor activity of the AKT inhibitor, ipatasertib, in combination with endocrine therapy and a CDK4/6 inhibitor for patients with hormone receptor positive (HR+)/HER2 negative metastatic breast cancer (MBC) (TAKTIC). J Clin Oncol. 38:10662020. View Article : Google Scholar

190 

Huang J, Zheng L, Sun Z and Li J: CDK4/6 inhibitor resistance mechanisms and treatment strategies (review). Int J Mol Med. 50:1282022. View Article : Google Scholar : PubMed/NCBI

191 

Piccart M, Hortobagyi GN, Campone M, Pritchard KI, Lebrun F, Ito Y, Noguchi S, Perez A, Rugo HS, Deleu I, et al: Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: Overall survival results from BOLERO-2†. Ann Oncol. 25:2357–2362. 2014. View Article : Google Scholar : PubMed/NCBI

192 

Lord CJ and Ashworth A: PARP inhibitors: Synthetic lethality in the clinic. Science. 355:1152–1158. 2017. View Article : Google Scholar : PubMed/NCBI

193 

Guney Eskiler G, Ozman Z, Haciefendi A and Cansaran-Duman D: Novel combination treatment of CDK 4/6 inhibitors with PARP inhibitors in triple negative breast cancer cells. Naunyn Schmiedebergs Arch Pharmacol. 396:1031–1041. 2023. View Article : Google Scholar : PubMed/NCBI

194 

Wu C, Peng S, Pilié PG, Geng C, Park S, Manyam GC, Lu Y, Yang G, Tang Z, Kondraganti S, et al: PARP and CDK4/6 inhibitor combination therapy induces apoptosis and suppresses neuroendocrine differentiation in prostate cancer. Mol Cancer Ther. 20:1680–1691. 2021. View Article : Google Scholar : PubMed/NCBI

195 

Zhu X, Chen L, Huang B, Li X, Yang L, Hu X, Jiang Y, Shao Z and Wang Z: Efficacy and mechanism of the combination of PARP and CDK4/6 inhibitors in the treatment of triple-negative breast cancer. J Exp Clin Cancer Res. 40:1222021. View Article : Google Scholar : PubMed/NCBI

196 

Curtin NJ and Szabo C: Poly(ADP-ribose) polymerase inhibition: Past, present and future. Nat Rev Drug Discov. 19:711–736. 2020. View Article : Google Scholar : PubMed/NCBI

197 

Jiang Z, Li W, Hu X, Zhang Q, Sun T, Cui S, Wang S, Ouyang Q, Yin Y, Geng C, et al: Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor-positive breast cancer (ACE): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 20:806–815. 2019. View Article : Google Scholar : PubMed/NCBI

198 

Reeves C: San Antonio breast cancer symposium 2021. Lancet Oncol. 23:e182022. View Article : Google Scholar

199 

Lok SW, Whittle JR, Vaillant F, The CE, Lo LL, Policheni AN, Bergin ART, Desai J, Ftouni S, Gandolfo LC, et al: A phase Ib dose-escalation and expansion study of the BCL2 inhibitor venetoclax combined with tamoxifen in ER and BCL2-positive metastatic breast cancer. Cancer Discov. 9:354–369. 2019. View Article : Google Scholar

200 

Lindeman GJ, Fernando TM, Bowen R, Jerzak KJ, Song X, Decker T, Boyle F, McCune S, Armstrong A, Shannon C, et al: VERONICA: Randomized phase II study of fulvestrant and venetoclax in ER-positive metastatic breast cancer Post-CDK4/6 inhibitors-efficacy, safety, and biomarker results. Clin Cancer Res. 28:3256–3267. 2022. View Article : Google Scholar : PubMed/NCBI

201 

Benvenuti C, Grinda T, Rassy E, Dixon-Douglas J, Ribeiro JM, Zambelli A, Santoro A and Pistilli B: Unveiling the potential of Cyclin-dependent kinases 4 and 6 inhibitors beyond progression in hormone receptor positive/human epidermal growth factor negative advanced breast cancer-a clinical review. Curr Treat Options Oncol. 25:1517–1537. 2024. View Article : Google Scholar : PubMed/NCBI

202 

Kubeczko M, Jarząb M, Gabryś D, Krzywon A, Cortez AJ and Xu AJ: Safety and feasibility of CDK4/6 inhibitors treatment combined with radiotherapy in patients with HR-positive/HER2-negative breast cancer. A systematic review and meta-analysis. Radiother Oncol. 187:1098392023. View Article : Google Scholar : PubMed/NCBI

203 

Lee CL, Oh P, Xu ES, Ma Y, Kim Y, Daniel AR and Kirsch DG: Blocking Cyclin-dependent kinase 4/6 during single dose versus fractionated radiation therapy leads to opposite effects on acute gastrointestinal toxicity in mice. Int J Radiat Oncol Biol Phys. 102:1569–1576. 2018. View Article : Google Scholar : PubMed/NCBI

204 

Naz S, Sowers A, Choudhuri R, Wissler M, Gamson J, Mathias A, Cook JA and Mitchell JB: Abemaciclib, a selective CDK4/6 inhibitor, enhances the radiosensitivity of Non-small cell lung cancer in vitro and in vivo. Clin Cancer Res. 24:3994–4005. 2018. View Article : Google Scholar : PubMed/NCBI

205 

Hagen KR, Zeng X, Lee MY, Tucker Kahn S, Harrison Pitner MK, Zaky SS, Liu Y, O'Regan RM, Deng X and Saavedra HI: Silencing CDK4 radiosensitizes breast cancer cells by promoting apoptosis. Cell Div. 8:102013. View Article : Google Scholar : PubMed/NCBI

206 

Whittaker S, Madani D, Joshi S, Chung SA, Johns T, Day B, Khasraw M and McDonald KL: Combination of palbociclib and radiotherapy for glioblastoma. Cell Death Discov. 3:170332017. View Article : Google Scholar : PubMed/NCBI

207 

Huang CY, Hsieh FS, Wang CY, Chen LJ, Chang SS, Tsai MH, Hung MH, Kuo CW, Shih CT, Chao TI and Chen KF: Palbociclib enhances radiosensitivity of hepatocellular carcinoma and cholangiocarcinoma via inhibiting ataxia telangiectasia-mutated kinase-mediated DNA damage response. Eur J Cancer. 102:10–22. 2018. View Article : Google Scholar : PubMed/NCBI

208 

Slamon DJ, Stroyakovskiy D, Yardley DA, Huang C, Fasching PA, Crown J, Bardia A, Chia S, Im S, Martin M, et al: Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2-early breast cancer: Primary results from the phase III NATALEE trial. J Clin Oncol. 41:LBA5002023. View Article : Google Scholar

209 

Becherini C, Visani L, Caini S, Bhattacharya IS, Kirby AM, Nader Marta G, Morgan G, Salvestrini V, Coles CE, Cortes J, et al: Safety profile of cyclin-dependent kinase (CDK) 4/6 inhibitors with concurrent radiation therapy: A systematic review and meta-analysis. Cancer Treat Rev. 119:1025862023. View Article : Google Scholar : PubMed/NCBI

210 

Franco R, Cao JQ, Yassa M and Hijal T: Safety of CDK4/6 inhibitors combined with radiotherapy in patients with metastatic breast cancer: A Review of the literature. Curr Oncol. 30:5485–5496. 2023. View Article : Google Scholar : PubMed/NCBI

211 

Ratosa I, Orazem M, Scoccimarro E, Steinacher M, Dominici L, Aquilano M, Cerbai C, Desideri I, Ribnikar D, Marinko T, et al: Cyclin-Dependent Kinase 4/6 inhibitors combined with radiotherapy for patients with metastatic breast cancer. Clin Breast Cancer. 20:495–502. 2020. View Article : Google Scholar : PubMed/NCBI

212 

Kawamoto T, Shikama N, Imano N, Kubota H, Kosugi T, Sekii S, Harada H, Yamada K, Naoi Y, Miyazawa K, et al: Incidence of and risk factors for non-hematologic toxicity with combined radiotherapy and CDK4/6 inhibitors in metastatic breast cancer using dose-volume parameters analysis: A multicenter cohort study. Breast Cancer. 30:282–292. 2023. View Article : Google Scholar

213 

Hashizume R, Zhang A, Mueller S, Prados MD, Lulla RR, Goldman S, Saratsis AM, Mazar AP, Stegh AH, Cheng SY, et al: Inhibition of DNA damage repair by the CDK4/6 inhibitor palbociclib delays irradiated intracranial atypical teratoid rhabdoid tumor and glioblastoma xenograft regrowth. Neuro Oncol. 18:1519–1528. 2016.PubMed/NCBI

214 

Pesch AM, Hirsh NH, Chandler BC, Michmerhuizen AR, Ritter CL, Androsiglio MP, Wilder-Romans K, Liu M, Gersch CL, Larios JM, et al: Short-term CDK4/6 inhibition radiosensitizes estrogen receptor-positive breast cancers. Clin Cancer Res. 26:6568–6580. 2020. View Article : Google Scholar : PubMed/NCBI

215 

Meattini I, Livi L, Lorito N, Becherini C, Bacci M, Visani L, Fozza A, Belgioia L, Loi M, Mangoni M, et al: Integrating radiation therapy with targeted treatments for breast cancer: From bench to bedside. Cancer Treat Rev. 108:1024172022. View Article : Google Scholar : PubMed/NCBI

216 

Zhang X, Zhu L, Zhang H, Chen S and Xiao Y: CAR-T cell therapy in hematological malignancies: Current opportunities and challenges. Front Immunol. 13:9271532022. View Article : Google Scholar : PubMed/NCBI

217 

Zhang ZZ, Wang T, Wang XF, Zhang YQ, Song SX and Ma CQ: Improving the ability of CAR-T cells to hit solid tumors: Challenges and strategies. Pharmacol Res. 175:1060362022. View Article : Google Scholar

218 

Lelliott EJ, Kong IY, Zethoven M, Ramsbottom KM, Martelotto LG, Meyran D, Zhu JJ, Costacurta M, Kirby L, Sandow JJ, et al: CDK4/6 inhibition promotes antitumor immunity through the induction of T-cell memory. Cancer Discov. 11:2582–2601. 2021. View Article : Google Scholar : PubMed/NCBI

219 

Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz SA, Chow L, Sohn J, Lee KS, et al: Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): A randomised phase 3 trial. Lancet Oncol. 19:904–915. 2018. View Article : Google Scholar : PubMed/NCBI

220 

Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, et al: Palbociclib in Hormone-Receptor-positive advanced breast cancer. N Engl J Med. 373:209–219. 2015. View Article : Google Scholar : PubMed/NCBI

221 

Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Petrakova K, Blackwell KL, Winer EP, et al: Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 29:1541–1547. 2018. View Article : Google Scholar : PubMed/NCBI

222 

Rugo HS, Huober J, García-Sáenz JA, Masuda N, Sohn JH, Andre VAM, Barriga S, Cox J and Goetz M: Management of Abemaciclib-associated adverse events in patients with hormone Receptor-positive, human epidermal growth factor receptor 2-Negative advanced breast cancer: Safety analysis of MONARCH 2 and MONARCH 3. Oncologist. 26:e53–e65. 2021. View Article : Google Scholar

223 

Spring LM, Zangardi ML, Moy B and Bardia A: Clinical management of potential toxicities and drug interactions related to Cyclin-Dependent kinase 4/6 inhibitors in breast cancer: Practical considerations and recommendations. Oncologist. 22:1039–1048. 2017. View Article : Google Scholar : PubMed/NCBI

224 

Asghar U, Witkiewicz AK, Turner NC and Knudsen ES: The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov. 14:130–146. 2015. View Article : Google Scholar : PubMed/NCBI

225 

Hassanzadeh A, Shomali N, Kamrani A, Soltani-Zangbar MS, Nasiri H and Akbari M: Cancer therapy by cyclin-dependent kinase inhibitors (CDKIs): Bench to bedside. EXCLI J. 23:862–882. 2024.PubMed/NCBI

226 

Zheng M, Zhang XY, Chen W, Xia F, Yang H, Yuan K and Yang P: Molecules inducing specific cyclin-dependent kinase degradation and their possible use in cancer therapy. Future Med Chem. 16:369–388. 2024. View Article : Google Scholar : PubMed/NCBI

227 

Majeski H, Okano A, Pasis A, Carlson C, Shakya A, Huang S, Hoskote Chourasia A, Fung LM and Liu Q: Discovery of CDK4/6 bifunctional degraders for ER+/HER2-breast cancer. J Clin Oncol. 14:10832023. View Article : Google Scholar

228 

Schott AF, Hurvitz S, Ma C, Hamilton E, Nanda R, Zahrah G, Hunter N, Tan AR, Telli M, Mesias JA, et al: Abstract GS3-03: GS3-03 ARV-471, a PROTAC® estrogen receptor (ER) degrader in advanced ER-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer: Phase 2 expansion (VERITAC) of a phase 1/2 study. Cancer Res. 83(Suppl 5): GS3–03. 2023.

229 

Bruls R: Treatment options beyond CDK4/6 inhibition. In: Medical Conferences; 2023

230 

Fassl A, Brain C, Abu-Remaileh M, Stukan I, Butter D, Stepien P, Feit AS, Bergholz J, Michowski W, Otto T, et al: Increased lysosomal biomass is responsible for the resistance of triple-negative breast cancers to CDK4/6 inhibition. Sci Adv. 6:eabb22102020. View Article : Google Scholar : PubMed/NCBI

231 

Hassan MA-K and Ates-Alagoz Z: Cyclin-dependent kinase 4/6 inhibitors against breast cancer. Mini Rev Med Chem. 23:412–428. 2023. View Article : Google Scholar

232 

Lv S, Yang J, Lin J, Huang X, Zhao H, Zhao C and Yang L: CDK4/6 inhibitors in lung cancer: Current practice and future directions. Eur Respir Rev. 33:2301452024. View Article : Google Scholar : PubMed/NCBI

233 

Du Q, Guo X, Wang M, Li Y, Sun X and Li Q: The application and prospect of CDK4/6 inhibitors in malignant solid tumors. J Hematol Oncol. 13:412020. View Article : Google Scholar : PubMed/NCBI

234 

Sun M, Dong L, Wang Y, Liu C, Du J, Wang B, Xing B, Yao X, Ren Y and Zhou X: The role of targeting CDK4/6 in cancer immunotherapy. Holist Integ Oncol. 3:322024. View Article : Google Scholar

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He F, Zhang Q, Chen Y, Ge S, Xie Y, Sun R, Wu Y and Xu J: The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review). Int J Mol Med 56: 123, 2025.
APA
He, F., Zhang, Q., Chen, Y., Ge, S., Xie, Y., Sun, R. ... Xu, J. (2025). The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review). International Journal of Molecular Medicine, 56, 123. https://doi.org/10.3892/ijmm.2025.5564
MLA
He, F., Zhang, Q., Chen, Y., Ge, S., Xie, Y., Sun, R., Wu, Y., Xu, J."The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review)". International Journal of Molecular Medicine 56.2 (2025): 123.
Chicago
He, F., Zhang, Q., Chen, Y., Ge, S., Xie, Y., Sun, R., Wu, Y., Xu, J."The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review)". International Journal of Molecular Medicine 56, no. 2 (2025): 123. https://doi.org/10.3892/ijmm.2025.5564
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Spandidos Publications style
He F, Zhang Q, Chen Y, Ge S, Xie Y, Sun R, Wu Y and Xu J: The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review). Int J Mol Med 56: 123, 2025.
APA
He, F., Zhang, Q., Chen, Y., Ge, S., Xie, Y., Sun, R. ... Xu, J. (2025). The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review). International Journal of Molecular Medicine, 56, 123. https://doi.org/10.3892/ijmm.2025.5564
MLA
He, F., Zhang, Q., Chen, Y., Ge, S., Xie, Y., Sun, R., Wu, Y., Xu, J."The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review)". International Journal of Molecular Medicine 56.2 (2025): 123.
Chicago
He, F., Zhang, Q., Chen, Y., Ge, S., Xie, Y., Sun, R., Wu, Y., Xu, J."The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review)". International Journal of Molecular Medicine 56, no. 2 (2025): 123. https://doi.org/10.3892/ijmm.2025.5564
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