Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review)

Chiangjong,Wararat; Chutipongtanate,Somchai; Hongeng,Suradej

doi:10.3892/ijo.2020.5099

Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review)

Authors:
- Wararat Chiangjong
- Somchai Chutipongtanate
- Suradej Hongeng
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Affiliations: Pediatric Translational Research Unit, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand, Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Published online on: July 10, 2020 https://doi.org/10.3892/ijo.2020.5099
Pages: 678-696
Copyright: © Chiangjong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cancer is currently ineffectively treated using therapeutic drugs, and is also able to resist drug action, resulting in increased side effects following drug treatment. A novel therapeutic strategy against cancer cells is the use of anticancer peptides (ACPs). The physicochemical properties, amino acid composition and the addition of chemical groups on the ACP sequence influences their conformation, net charge and orientation of the secondary structure, leading to an effect on targeting specificity and ACP‑cell interaction, as well as peptide penetrating capability, stability and efficacy. ACPs have been developed from both naturally occurring and modified peptides by substituting neutral or anionic amino acid residues with cationic amino acid residues, or by adding a chemical group. The modified peptides lead to an increase in the effectiveness of cancer therapy. Due to this effectiveness, ACPs have recently been improved to form drugs and vaccines, which have sequentially been evaluated in various phases of clinical trials. The development of the ACPs remains focused on generating newly modified ACPs for clinical application in order to decrease the incidence of new cancer cases and decrease the mortality rate. The present review could further facilitate the design of ACPs and increase efficacious ACP therapy in the near future.

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1	Wang SH and Yu J: Structure-based design for binding peptides in anti-cancer therapy. Biomaterials. 156:1–15. 2018. View Article : Google Scholar
2	Wang X, Zhang L, Ding N, Yang X, Zhang J, He J, Li Z and Sun LQ: Identification and characterization of DNAzymes targeting DNA methyltransferase I for suppressing bladder cancer proliferation. Biochem Biophys Res Commun. 461:329–333. 2015. View Article : Google Scholar : PubMed/NCBI
3	Ingram JR, Blomberg OS, Rashidian M, Ali L, Garforth S, Fedorov E, Fedorov AA, Bonanno JB, Le Gall C, Crowley S, et al: Anti-CTLA-4 therapy requires an Fc domain for efficacy. Proc Natl Acad Sci USA. 115:3912–3917. 2018. View Article : Google Scholar : PubMed/NCBI
4	Di JX and Zhang HY: C188-9 a small-molecule STAT3 inhibitor, exerts an antitumor effect on head and neck squamous cell carcinoma. Anticancer Drugs. 30:846–853. 2019. View Article : Google Scholar : PubMed/NCBI
5	Brun S, Bassissi F, Serdjebi C, Novello M, Tracz J, Autelitano F, Guillemot M, Fabre P, Courcambeck J, Ansaldi C, et al: GNS561, a new lysosomotropic small molecule, for the treatment of intrahe-patic cholangiocarcinoma. Invest New Drugs. 37:1135–1145. 2019. View Article : Google Scholar : PubMed/NCBI
6	Jahangirian H, Kalantari K, Izadiyan Z, Rafiee-Moghaddam R, Shameli K and Webster TJ: A review of small molecules and drug delivery applications using gold and iron nanoparticles. Int J Nanomedicine. 14:1633–1657. 2019. View Article : Google Scholar : PubMed/NCBI
7	Tyagi A, Tuknait A, Anand P, Gupta S, Sharma M, Mathur D, Joshi A, Singh S, Gautam A and Raghava GP: CancerPPD: A database of anticancer peptides and proteins. Nucleic Acids Res. 43(Database Issue): D837–D843. 2015. View Article : Google Scholar :
8	Thundimadathil J: Cancer treatment using peptides: Current therapies and future prospects. J Amino Acids. 2012:9673472012. View Article : Google Scholar
9	Vlieghe P, Lisowski V, Martinez J and Khrestchatisky M: Synthetic therapeutic peptides: Science and market. Drug Discov Today. 15:40–56. 2010. View Article : Google Scholar
10	Otvos L Jr: Peptide-based drug design: Here and now. Methods Mol Biol. 494:1–8. 2008. View Article : Google Scholar : PubMed/NCBI
11	Hoskin DW and Ramamoorthy A: Studies on anticancer activities of antimicrobial peptides. Biochim Biophys Acta. 1778:357–375. 2008. View Article : Google Scholar
12	Rodrigues EG, Dobroff AS, Taborda CP and Travassos LR: Antifungal and antitumor models of bioactive protective peptides. An Acad Bras Cienc. 81:503–520. 2009. View Article : Google Scholar : PubMed/NCBI
13	Droin N, Hendra JB, Ducoroy P and Solary E: Human defensins as cancer biomarkers and antitumour molecules. J Proteomics. 72:918–927. 2009. View Article : Google Scholar : PubMed/NCBI
14	Simons K and Ikonen E: How cells handle cholesterol. Science. 290:1721–1726. 2000. View Article : Google Scholar : PubMed/NCBI
15	Sok M, Sentjurc M and Schara M: Membrane fluidity characteristics of human lung cancer. Cancer Lett. 139:215–220. 1999. View Article : Google Scholar : PubMed/NCBI
16	Zwaal RF and Schroit AJ: Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood. 89:1121–1132. 1997. View Article : Google Scholar : PubMed/NCBI
17	Schweizer F: Cationic amphiphilic peptides with cancer-selective toxicity. Eur J Pharmacol. 625:190–194. 2009. View Article : Google Scholar : PubMed/NCBI
18	Utsugi T, Schroit AJ, Connor J, Bucana CD and Fidler IJ: Elevated expression of phosphatidylserine in the outer membrane leaflet of human tumor cells and recognition by activated human blood monocytes. Cancer Res. 51:3062–3066. 1991.PubMed/NCBI
19	Harris F, Dennison SR, Singh J and Phoenix DA: On the selectivity and efficacy of defense peptides with respect to cancer cells. Med Res Rev. 33:190–234. 2013. View Article : Google Scholar
20	Li G, Huang Y, Feng Q and Chen Y: Tryptophan as a probe to study the anticancer mechanism of action and specificity of alpha-helical anticancer peptides. Molecules. 19:12224–12241. 2014. View Article : Google Scholar : PubMed/NCBI
21	Marqus S, Pirogova E and Piva TJ: Evaluation of the use of therapeutic peptides for cancer treatment. J Biomed Sci. 24:212017. View Article : Google Scholar : PubMed/NCBI
22	Roudi R, Syn NL and Roudbary M: Antimicrobial peptides as biologic and immunotherapeutic agents against Cancer: A comprehensive overview. Front Immunol. 8:13202017. View Article : Google Scholar : PubMed/NCBI
23	Alves AC, Ribeiro D, Nunes C and Reis S: Biophysics in cancer: The relevance of drug-membrane interaction studies. Biochim Biophys Acta. 1858:2231–2244. 2016. View Article : Google Scholar : PubMed/NCBI
24	Yamaji-Hasegawa A and Tsujimoto M: Asymmetric distribution of phospholipids in biomembranes. Biol Pharm Bull. 29:1547–1553. 2006. View Article : Google Scholar : PubMed/NCBI
25	Clark MR: Flippin' lipids. Nat Immunol. 12:373–375. 2011. View Article : Google Scholar : PubMed/NCBI
26	Deliconstantinos G: Physiological aspects of membrane lipid fluidity in malignancy. Anticancer Res. 7:1011–1021. 1987.PubMed/NCBI
27	Ran S, Downes A and Thorpe PE: Increased exposure of anionic phospholipids on the surface of tumor blood vessels. Cancer Res. 62:6132–6140. 2002.PubMed/NCBI
28	Stafford JH and Thorpe PE: Increased exposure of phosphati-dylethanolamine on the surface of tumor vascular endothelium. Neoplasia. 13:299–308. 2011. View Article : Google Scholar : PubMed/NCBI
29	Barcelo-Coblijn G, Martin ML, de Almeida RF, Noguera-Salva MA, Marcilla-Etxenike A, Guardiola-Serrano F, Lüth A, Kleuser B, Halver JE and Escribá PV: Sphingomyelin and sphin-gomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy. Proc Natl Acad Sci USA. 108:19569–19574. 2011. View Article : Google Scholar
30	Preetha A, Huilgol N and Banerjee R: Comparison of paclitaxel penetration in normal and cancerous cervical model monolayer membranes. Colloids Surf B Biointerfaces. 53:179–186. 2006. View Article : Google Scholar : PubMed/NCBI
31	Zhao L, Feng SS and Go ML: Investigation of molecular interactions between paclitaxel and DPPC by Langmuir film balance and differential scanning calorimetry. J Pharm Sci. 93:86–98. 2004. View Article : Google Scholar
32	Logozzi M, Spugnini E, Mizzoni D, Di Raimo R and Fais S: Extracellular acidity and increased exosome release as key phenotypes of malignant tumors. Cancer Metastasis Rev. 38:93–101. 2019. View Article : Google Scholar : PubMed/NCBI
33	Cardone RA, Casavola V and Reshkin SJ: The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis. Nat Rev Cancer. 5:786–795. 2005. View Article : Google Scholar : PubMed/NCBI
34	Jobin ML and Alves ID: On the importance of electrostatic interactions between cell penetrating peptides and membranes: A pathway toward tumor cell selectivity? Biochimie. 107:154–159. 2014. View Article : Google Scholar : PubMed/NCBI
35	Peyressatre M, Prevel C, Pellerano M and Morris MC: Targeting cyclin-dependent kinases in human cancers: From small molecules to Peptide inhibitors. Cancers (Basel). 7:179–237. 2015. View Article : Google Scholar
36	Raucher D and Ryu JS: Cell-penetrating peptides: Strategies for anticancer treatment. Trends Mol Med. 21:560–570. 2015. View Article : Google Scholar : PubMed/NCBI
37	Li J, Tan S, Chen X, Zhang CY and Zhang Y: Peptide aptamers with biological and therapeutic applications. Curr Med Chem. 18:4215–4222. 2011. View Article : Google Scholar : PubMed/NCBI
38	Fuertes MA, Castilla J, Alonso C and Perez JM: Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways. Curr Med Chem. 10:257–266. 2003. View Article : Google Scholar : PubMed/NCBI
39	Horwitz SB: Taxol (paclitaxel): Mechanisms of action. Ann Oncol. 5(Suppl 6): S3–S6. 1994.PubMed/NCBI
40	Huang Y, Li X, Sha H, Zhang L, Bian X, Han X and Liu B: Tumor-penetrating peptide fused to a pro-apoptotic peptide facilitates effective gastric cancer therapy. Oncol Rep. 37:2063–2070. 2017. View Article : Google Scholar : PubMed/NCBI
41	Zhang B, Shi W, Li J, Liao C, Yang L, Huang W and Qian H: Synthesis and biological evaluation of novel peptides based on antimicrobial peptides as potential agents with antitumor and multidrug resistance-reversing activities. Chem Biol Drug Des. 90:972–980. 2017. View Article : Google Scholar : PubMed/NCBI
42	Ramsey JD and Flynn NH: Cell-penetrating peptides transport therapeutics into cells. Pharmacol Ther. 154:78–86. 2015. View Article : Google Scholar : PubMed/NCBI
43	Kapoor P, Singh H, Gautam A, Chaudhary K, Kumar R and Raghava GP: TumorHoPe: A database of tumor homing peptides. PLoS One. 7:e351872012. View Article : Google Scholar : PubMed/NCBI
44	Ghasemy S, Garcia-Pindado J, Aboutalebi F, Dormiani K, Teixido M and Malakoutikhah M: Fine-tuning the physicochemical properties of peptide-based blood-brain barrier shuttles. Bioorg Med Chem. 26:2099–2106. 2018. View Article : Google Scholar : PubMed/NCBI
45	Buckton LK and McAlpine SR: Improving the cell permeability of polar cyclic peptides by replacing residues with alkylated amino acids, asparagines, and d-Amino Acids. Org Lett. 20:506–509. 2018. View Article : Google Scholar : PubMed/NCBI
46	Perry SR, Hill TA, de Araujo AD, Hoang HN and Fairlie DP: Contiguous hydrophobic and charged surface patches in short helix-constrained peptides drive cell permeability. Org Biomol Chem. 16:367–371. 2018. View Article : Google Scholar
47	Shoombuatong W, Schaduangrat N and Nantasenamat C: Unraveling the bioactivity of anticancer peptides as deduced from machine learning. EXCLI J. 17:734–752. 2018.PubMed/NCBI
48	Dai YX, Cai XG, Shi W, Bi XZ, Su X, Pan MB, Li HL, Lin HY, Huang WL and Qian H: Pro-apoptotic cationic host defense peptides rich in lysine or arginine to reverse drug resistance by disrupting tumor cell membrane. Amino Acids. 49:1601–1610. 2017. View Article : Google Scholar : PubMed/NCBI
49	Navarro S, Aleu J, Jimenez M, Boix E, Cuchillo CM and Nogues MV: The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell lines takes place through its aggregation on the cell membrane. Cell Mol Life Sci. 65:324–337. 2008. View Article : Google Scholar
50	Midoux P, Kichler A, Boutin V, Maurizot JC and Monsigny M: Membrane permeabilization and efficient gene transfer by a peptide containing several histidines. Bioconjug Chem. 9:260–267. 1998. View Article : Google Scholar : PubMed/NCBI
51	Yamaguchi Y, Yamamoto K, Sato Y, Inoue S, Morinaga T and Hirano E: Combination of aspartic acid and glutamic acid inhibits tumor cell proliferation. Biomed Res. 37:153–159. 2016. View Article : Google Scholar : PubMed/NCBI
52	Oancea E, Teruel MN, Quest AF and Meyer T: Green fluorescent protein (GFP)-tagged cysteine-rich domains from protein kinase C as fluorescent indicators for diacylglycerol signaling in living cells. J Cell Biol. 140:485–498. 1998. View Article : Google Scholar : PubMed/NCBI
53	Shamova O, Orlov D, Stegemann C, Czihal P, Hoffmann R, Brogden K, Kolodkin N, Sakuta G, Tossi A, Sahl HG, et al: ChBac3.4: A Novel proline-rich antimicrobial peptide from goat leukocytes. Int J Pept Res Ther. 15:107–119. 2009. View Article : Google Scholar
54	Maddocks ODK, Athineos D, Cheung EC, Lee P, Zhang T, van den Broek NJF, Mackay GM, Labuschagne CF, Gay D, Kruiswijk F, et al: Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature. 544:372–376. 2017. View Article : Google Scholar : PubMed/NCBI
55	Kawaguchi K, Han Q, Li S, Tan Y, Igarashi K, Kiyuna T, Miyake K, Miyake M, Chmielowski B, Nelson SD, et al: Targeting methionine with oral recombinant methioninase (o-rMETase) arrests a patient-derived orthotopic xenograft (PDOX) model of BRAF-V600E mutant melanoma: Implications for chronic clinical cancer therapy and prevention. Cell Cycle. 17:356–361. 2018. View Article : Google Scholar :
56	Gueron G, Anselmino N, Chiarella P, Ortiz EG, Lage Vickers S, Paez AV, Giudice J, Contin MD, Leonardi D, Jaworski F, et al: Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis. Cell Death Dis. 9:1402018. View Article : Google Scholar : PubMed/NCBI
57	Dennison SR, Whittaker M, Harris F and Phoenix DA: Anticancer alpha-helical peptides and structure/function relationships underpinning their interactions with tumour cell membranes. Curr Protein Pept Sci. 7:487–499. 2006. View Article : Google Scholar : PubMed/NCBI
58	Marchand C, Krajewski K, Lee HF, Antony S, Johnson AA, Amin R, Roller P, Kvaratskhelia M and Pommier Y: Covalent binding of the natural antimicrobial peptide indolicidin to DNA abasic sites. Nucleic Acids Res. 34:5157–5165. 2006. View Article : Google Scholar : PubMed/NCBI
59	Barras D, Chevalier N, Zoete V, Dempsey R, Lapouge K, Olayioye MA, Michielin O and Widmann C: A WXW motif is required for the anticancer activity of the TAT-RasGAP317-326 peptide. J Biol Chem. 289:23701–23711. 2014. View Article : Google Scholar : PubMed/NCBI
60	Ahmaditaba MA, Shahosseini S, Daraei B, Zarghi A and Houshdar Tehrani MH: Design, synthesis, and biological evaluation of new peptide analogues as selective cox-2 inhibitors. Arch Pharm (Weinheim). 350:e17001582017. View Article : Google Scholar
61	Bhunia D, Mondal P, Das G, Saha A, Sengupta P, Jana J, Mohapatra S, Chatterjee S and Ghosh S: Spatial position regulates power of tryptophan: Discovery of a major-groove-specific nuclear-localizing, cell-penetrating tetrapeptide. J Am Chem Soc. 140:1697–1714. 2018. View Article : Google Scholar
62	Huang YB, Wang XF, Wang HY, Liu Y and Chen Y: Studies on mechanism of action of anticancer peptides by modulation of hydrophobicity within a defined structural framework. Mol Cancer Ther. 10:416–426. 2011. View Article : Google Scholar : PubMed/NCBI
63	Yang QZ, Wang C, Lang L, Zhou Y, Wang H and Shang DJ: Design of potent, non-toxic anticancer peptides based on the structure of the antimicrobial peptide, temporin-1CEa. Arch Pharm Res. 36:1302–1310. 2013. View Article : Google Scholar : PubMed/NCBI
64	Dennison SR, Harris F, Bhatt T, Singh J and Phoenix DA: A theoretical analysis of secondary structural characteristics of anticancer peptides. Mol Cell Biochem. 333:129–135. 2010. View Article : Google Scholar
65	Wu JM, Jan PS, Yu HC, Haung HY, Fang HJ, Chang YI, Cheng JW and Chen HM: Structure and function of a custom anticancer peptide, CB1a. Peptides. 30:839–848. 2009. View Article : Google Scholar : PubMed/NCBI
66	Lins L and Brasseur R: Tilted peptides: A structural motif involved in protein membrane insertion? J Pept Sci. 14:416–422. 2008. View Article : Google Scholar
67	Lins L, Decaffmeyer M, Thomas A and Brasseur R: Relationships between the orientation and the structural properties of peptides and their membrane interactions. Biochim Biophys Acta. 1778:1537–1544. 2008. View Article : Google Scholar : PubMed/NCBI
68	Mandal PK, Gao F, Lu Z, Ren Z, Ramesh R, Birtwistle JS, Kaluarachchi KK, Chen X, Bast RC Jr, Liao WS, et al: Potent and selective phosphopeptide mimetic prodrugs targeted to the Src homology 2 (SH2) domain of signal transducer and activator of transcription 3. J Med Chem. 54:3549–3563. 2011. View Article : Google Scholar : PubMed/NCBI
69	Gabernet G, Gautschi D, Muller AT, Neuhaus CS, Armbrecht L, Dittrich PS, Hiss JA and Schneider G: In silico design and optimization of selective membranolytic anticancer peptides. Sci Rep. 9:112822019. View Article : Google Scholar : PubMed/NCBI
70	Singh M, Kumar V, Sikka K, Thakur R, Harioudh MK, Mishra DP, Ghosh JK and Siddiqi MI: Computational design of biologically active anticancer peptides and their interactions with heterogeneous POPC/POPS Lipid membranes. J Chem Inf Model. 60:332–341. 2020. View Article : Google Scholar
71	Ray T, Kar D and Pal A, Mukherjee S, Das C and Pal A: Molecular targeting of breast and colon cancer cells by PAR1 mediated apoptosis through a novel pro-apoptotic peptide. Apoptosis. 23:679–694. 2018. View Article : Google Scholar : PubMed/NCBI
72	Bohmova E, Machova D, Pechar M, Pola R, Venclikova K, Janouskova O and Etrych T: Cell-penetrating peptides: A useful tool for the delivery of various cargoes into cells. Physiol Res. 67(Suppl 2): S267–S279. 2018. View Article : Google Scholar : PubMed/NCBI
73	Levely ME, Mitchell MA and Nicholas JA: Synthetic immunogens constructed from T-cell and B-cell stimulating peptides (T:B chimeras): Preferential stimulation of unique T- and B-cell specificities is influenced by immunogen configuration. Cell Immunol. 125:65–78. 1990. View Article : Google Scholar : PubMed/NCBI
74	Asao T, Takahashi F and Takahashi K: Resistance to molecu-larly targeted therapy in non-small-cell lung cancer. Respir Investig. 57:20–26. 2019. View Article : Google Scholar
75	Zhang H, Han D, Lv T, Liu K, Yang Y, Xu X and Chen Y: Novel peptide myristoly-CM4 induces selective cytotoxicity in leukemia K562/MDR and Jurkat cells by necrosis and/or apop-tosis pathway. Drug Des Devel Ther. 13:2153–2167. 2019. View Article : Google Scholar :
76	Chen YQ, Min C, Sang M, Han YY, Ma X, Xue XQ and Zhang SQ: A cationic amphiphilic peptide ABP-CM4 exhibits selective cytotoxicity against leukemia cells. Peptides. 31:1504–1510. 2010. View Article : Google Scholar : PubMed/NCBI
77	Jiang R, Du X and Lonnerdal B: Comparison of bioactivities of talactoferrin and lactoferrins from human and bovine milk. J Pediatr Gastroenterol Nutr. 59:642–652. 2014. View Article : Google Scholar : PubMed/NCBI
78	Tyagi A, Kapoor P, Kumar R, Chaudhary K, Gautam A and Raghava GP: In silico models for designing and discovering novel anticancer peptides. Sci Rep. 3:29842013. View Article : Google Scholar : PubMed/NCBI
79	Hajisharifi Z, Piryaiee M, Mohammad Beigi M, Behbahani M and Mohabatkar H: Predicting anticancer peptides with Chou's pseudo amino acid composition and investigating their muta-genicity via Ames test. J Theor Biol. 341:34–40. 2014. View Article : Google Scholar
80	Chen W, Feng PM, Lin H and Chou KC: iRSpot-PseDNC: Identify recombination spots with pseudo dinucleotide composition. Nucleic Acids Res. 41:e682013. View Article : Google Scholar : PubMed/NCBI
81	Grisoni F, Neuhaus C, Gabernet G, Muller A, Hiss J and Schneider G: Designing anticancer peptides by constructive machine learning. ChemMedChem. 13:1300–1302. 2018. View Article : Google Scholar : PubMed/NCBI
82	Kozlowska K, Nowak J, Kwiatkowski B and Cichorek M: ESR study of plasmatic membrane of the transplantable melanoma cells in relation to their biological properties. Exp Toxicol Pathol. 51:89–92. 1999. View Article : Google Scholar : PubMed/NCBI
83	Mai JC, Mi Z, Kim SH, Ng B and Robbins PD: A proapoptotic peptide for the treatment of solid tumors. Cancer Res. 61:7709–7712. 2001.PubMed/NCBI
84	Zhang W, Li J, Liu LW, Wang KR, Song JJ, Yan JX, Li ZY, Zhang BZ and Wang R: A novel analog of antimicrobial peptide Polybia-MPI, with thioamide bond substitution, exhibits increased therapeutic efficacy against cancer and diminished toxicity in mice. Peptides. 31:1832–1838. 2010. View Article : Google Scholar : PubMed/NCBI
85	Sinthuvanich C, Veiga AS, Gupta K, Gaspar D, Blumenthal R and Schneider JP: Anticancer β-hairpin peptides: Membrane-induced folding triggers activity. J Am Chem Soc. 134:6210–6217. 2012. View Article : Google Scholar : PubMed/NCBI
86	Gaspar D, Veiga AS, Sinthuvanich C, Schneider JP and Castanho MA: Anticancer peptide SVS-1: Efficacy precedes membrane neutralization. Biochemistry. 51:6263–6265. 2012. View Article : Google Scholar : PubMed/NCBI
87	Negi B, Kumar D and Rawat DS: Marine peptides as anticancer agents: A remedy to mankind by nature. Curr Protein Pept Sci. 18:885–904. 2017. View Article : Google Scholar
88	Lemeshko VV: Electrical potentiation of the membrane permeabilization by new peptides with anticancer properties. Biochim Biophys Acta. 1828:1047–1056. 2013. View Article : Google Scholar
89	Liu X, Cao R, Wang S, Jia J and Fei H: Amphipathicity determines different cytotoxic mechanisms of lysine- or arginine-rich cationic hydrophobic peptides in cancer cells. J Med Chem. 59:5238–5247. 2016. View Article : Google Scholar : PubMed/NCBI
90	Hu C, Chen X, Zhao W, Chen Y and Huang Y: Design and modification of anticancer peptides. Drug Des. 5:1000138–1000147. 2016. View Article : Google Scholar
91	Boohaker RJ, Lee MW, Vishnubhotla P, Perez JM and Khaled AR: The use of therapeutic peptides to target and to kill cancer cells. Curr Med Chem. 19:3794–3804. 2012. View Article : Google Scholar : PubMed/NCBI
92	Bidwell GL III and Raucher D: Therapeutic peptides for cancer therapy. Part I-peptide inhibitors of signal transduction cascades. Expert Opin Drug Deliv. 6:1033–1047. 2009. View Article : Google Scholar : PubMed/NCBI
93	Raucher D, Moktan S, Massodi I and Bidwell GL III: Therapeutic peptides for cancer therapy. Part II-cell cycle inhibitory peptides and apoptosis-inducing peptides. Expert Opin Drug Deliv. 6:1049–1064. 2009. View Article : Google Scholar : PubMed/NCBI
94	Ulasov IV, Borovjagin AV, Timashev P, Cristofanili M and Welch DR: KISS1 in breast cancer progression and autophagy. Cancer Metastasis Rev. 38:493–506. 2019. View Article : Google Scholar : PubMed/NCBI
95	Lamidi OF, Sani M, Lazzari P, Zanda M and Fleming IN: The tubulysin analogue KEMTUB10 induces apoptosis in breast cancer cells via p53, Bim and Bcl-2. J Cancer Res Clin Oncol. 141:1575–1583. 2015. View Article : Google Scholar : PubMed/NCBI
96	Wang C, Chen YW, Zhang L, Gong XG, Zhou Y and Shang DJ: Melanoma cell surface-expressed phosphatidylserine as a therapeutic target for cationic anticancer peptide, temporin-1CEa. J Drug Target. 24:548–556. 2016. View Article : Google Scholar
97	Cao XW, Yang XZ, Du X, Fu LY, Zhang TZ, Shan HW, Zhao J and Wang FJ: Structure optimisation to improve the delivery efficiency and cell selectivity of a tumour-targeting cell-penetrating peptide. J Drug Target. 26:777–792. 2018. View Article : Google Scholar : PubMed/NCBI
98	Shull AY, Hu CA and Teng Y: Zebrafish as a model to evaluate peptide-related cancer therapies. Amino Acids. 49:1907–1913. 2017. View Article : Google Scholar : PubMed/NCBI
99	Leite ML, da Cunha NB and Costa FF: Antimicrobial peptides, nanotechnology, and natural metabolites as novel approaches for cancer treatment. Pharmacol Ther. 183:160–176. 2018. View Article : Google Scholar
100	Sun T, Zhang YS, Pang B, Hyun DC, Yang M and Xia Y: Engineered nanoparticles for drug delivery in cancer therapy. Angew Chem Int Ed Engl. 53:12320–12364. 2014.PubMed/NCBI
101	Dossa F, Acuna SA, Rickles AS, Berho M, Wexner SD, Quereshy FA, Baxter NN and Chadi SA: Association between adjuvant chemotherapy and overall survival in patients with rectal cancer and pathological complete response after neoadjuvant chemotherapy and resection. JAMA Oncol. 4:930–937. 2018. View Article : Google Scholar : PubMed/NCBI
102	Xu J, Khan AR, Fu M, Wang R, Ji J and Zhai G: Cell-penetrating peptide: A means of breaking through the physiological barriers of different tissues and organs. J Control Release. 309:106–124. 2019. View Article : Google Scholar : PubMed/NCBI
103	Duarte D, Fraga AG, Pedrosa J, Martel F and Vale N: Increasing the potential of cell-penetrating peptides for cancer therapy using a new pentagonal scaffold. Eur J Pharmacol. 860:1725542019. View Article : Google Scholar : PubMed/NCBI
104	Park SE, Sajid MI, Parang K and Tiwari RK: Cyclic cell-penetrating peptides as efficient intracellular drug delivery tools. Mol Pharm. 16:3727–3743. 2019. View Article : Google Scholar : PubMed/NCBI
105	Copolovici DM, Langel K, Eriste E and Langel U: Cell-penetrating peptides:Design, synthesis, and applications. ACS Nano. 8:1972–1994. 2014. View Article : Google Scholar : PubMed/NCBI
106	Rothbard JB, Jessop TC, Lewis RS, Murray BA and Wender PA: Role of membrane potential and hydrogen bonding in the mechanism of translocation of guanidinium-rich peptides into cells. J Am Chem Soc. 126:9506–9507. 2004. View Article : Google Scholar : PubMed/NCBI
107	Guidotti G, Brambilla L and Rossi D: Cell-penetrating peptides: From basic research to clinics. Trends Pharmacol Sci. 38:406–424. 2017. View Article : Google Scholar : PubMed/NCBI
108	Pujals S and Giralt E: Proline-rich, amphipathic cell-penetrating peptides. Adv Drug Deliv Rev. 60:473–484. 2008. View Article : Google Scholar : PubMed/NCBI
109	Marks JR, Placone J, Hristova K and Wimley WC: Spontaneous membrane-translocating peptides by orthogonal high-throughput screening. J Am Chem Soc. 133:8995–9004. 2011. View Article : Google Scholar : PubMed/NCBI
110	Koren E and Torchilin VP: Cell-penetrating peptides: Breaking through to the other side. Trends Mol Med. 18:385–393. 2012. View Article : Google Scholar : PubMed/NCBI
111	Kamei N, Onuki Y, Takayama K and Takeda-Morishita M: Mechanistic study of the uptake/permeation of cell-penetrating peptides across a caco-2 monolayer and their stimulatory effect on epithelial insulin transport. J Pharm Sci. 102:3998–4008. 2013. View Article : Google Scholar : PubMed/NCBI
112	Chen Y, Xie X, Wu A, Wang L, Hu Y, Zhang H and Li Y: A synthetic cell-penetrating peptide derived from nuclear localization signal of EPS8 exerts anticancer activity against acute myeloid leukemia. J Exp Clin Cancer Res. 37:122018. View Article : Google Scholar : PubMed/NCBI
113	Lyu L, Huang LQ, Huang T, Xiang W, Yuan JD and Zhang CH: Cell-penetrating peptide conjugates of gambogic acid enhance the antitumor effect on human bladder cancer EJ cells through ROS-mediated apoptosis. Drug Des Devel Ther. 12:743–756. 2018. View Article : Google Scholar : PubMed/NCBI
114	Benergossi J, Calixto G, Fonseca-Santos B, Aida KL, de Cassia Negrini T, Duque C, Gremiao MP and Chorilli M: Highlights in peptide nanoparticle carriers intended to oral diseases. Curr Top Med Chem. 15:345–355. 2015. View Article : Google Scholar : PubMed/NCBI
115	Meng F, Han N and Yeo Y: Organic nanoparticle systems for spatiotemporal control of multimodal chemotherapy. Expert Opin Drug Deliv. 14:427–446. 2017. View Article : Google Scholar :
116	Conibear AC, Schmid A, Kamalov M, Becker CFW and Bello C: Recent advances in peptide-based approaches for cancer treatment. Curr Med Chem. 27:1174–1205. 2017. View Article : Google Scholar : PubMed/NCBI
117	Asadzadeh Z, Mohammadi H, Safarzadeh E, Hemmatzadeh M, Mahdian-Shakib A, Jadidi-Niaragh F, Azizi G and Baradaran B: The paradox of Th17 cell functions in tumor immunity. Cell Immunol. 322:15–25. 2017. View Article : Google Scholar : PubMed/NCBI
118	Darabi A, Thuring C and Paulsson KM: HLA-I antigen presentation and tapasin influence immune responses against malignant brain tumors-considerations for successful immunotherapy. Anticancer Agents Med Chem. 14:1094–1100. 2014. View Article : Google Scholar
119	Li M, Shi HS, Zhang HL, Luo ZC, Wan Y, Lu L, Luo ST and Yang L: bFGF peptide combined with the pVAX-8CpG plasmid as adjuvant is a novel anticancer vaccine inducing effective immune responses against Lewis lung carcinoma. Mol Med Rep. 5:625–630. 2012. View Article : Google Scholar
120	Wang W, Li Y, Wang Y, Ren S, Li Y and Wang B: Polyactin A is a novel and potent immunological adjuvant for peptide-based cancer vaccine. Int Immunopharmacol. 54:95–102. 2018. View Article : Google Scholar
121	Jin H, Wan C, Zou Z, Zhao G, Zhang L, Geng Y, Chen T, Huang A, Jiang F, Feng JP, et al: Tumor ablation and therapeutic immunity induction by an injectable peptide hydrogel. ACS Nano. 12:3295–3310. 2018. View Article : Google Scholar : PubMed/NCBI
122	Kakwere H, Ingham ES, Allen R, Mahakian LM, Tam SM, Zhang H, Silvestrini MT, Lewis JS and Ferrara KW: Toward personalized peptide-based cancer nanovaccines: A facile and versatile synthetic approach. Bioconjug Chem. 28:2756–2771. 2017. View Article : Google Scholar : PubMed/NCBI
123	Apostolopoulos V and McKenzie IF: Cellular mucins: Targets for immunotherapy. Crit Rev Immunol. 14:293–309. 1994. View Article : Google Scholar : PubMed/NCBI
124	Obara W, Eto M, Mimata H, Kohri K, Mitsuhata N, Miura I, Shuin T, Miki T, Koie T, Fujimoto H, et al: A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder. Ann Oncol. 28:798–803. 2017. View Article : Google Scholar
125	Antonilli M, Rahimi H, Visconti V, Napoletano C, Ruscito I, Zizzari IG, Caponnetto S, Barchiesi G, Iadarola R, Pierelli L, et al: Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial. Int J Oncol. 48:1369–1378. 2016. View Article : Google Scholar : PubMed/NCBI
126	Asahara S, Takeda K, Yamao K, Maguchi H and Yamaue H: Phase I/II clinical trial using HLA-A24-restricted peptide vaccine derived from KIF20A for patients with advanced pancreatic cancer. J Transl Med. 11:2912013. View Article : Google Scholar : PubMed/NCBI
127	Rausch S, Gouttefangeas C, Hennenlotter J, Laske K, Walter K, Feyerabend S, Chandran PA, Kruck S, Singh-Jasuja H, Frick A, et al: Results of a Phase 1/2 Study in Metastatic Renal Cell Carcinoma Patients Treated with a Patient-specific Adjuvant Multi-peptide Vaccine after Resection of Metastases. Eur Urol Focus. 5:604–607. 2019. View Article : Google Scholar
128	Dutoit V, Migliorini D, Ranzanici G, Marinari E, Widmer V, Lobrinus JA, Momjian S, Costello J, Walker PR, Okada H, et al: Antigenic expression and spontaneous immune responses support the use of a selected peptide set from the IMA950 glio-blastoma vaccine for immunotherapy of grade II and III glioma. Oncoimmunology. 7:e13919722018. View Article : Google Scholar
129	Lilleby W, Gaudernack G, Brunsvig PF, Vlatkovic L, Schulz M, Mills K, Hole KH and Inderberg EM: Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer. Cancer Immunol Immunother. 66:891–901. 2017. View Article : Google Scholar : PubMed/NCBI
130	Talebi S, Bolhassani A, Azad TM, Arashkia A and Modaresi MH: Immuno-stimulating peptide derived from HMGB1 is more effective than the N-terminal domain of Gp96 as an endogenous adjuvant for improvement of protein vaccines. Protein Pept Lett. 24:190–196. 2017. View Article : Google Scholar
131	Glover S, Delaney M, Dematte C, Kornberg L, Frasco M, Tran-Son-Tay R and Benya RV: Phosphorylation of focal adhesion kinase tyrosine 397 critically mediates gastrin-releasing peptide's morphogenic properties. J Cell Physiol. 199:77–88. 2004. View Article : Google Scholar : PubMed/NCBI
132	Schally AV, Zhang X, Cai R, Hare JM, Granata R and Bartoli M: Actions and potential therapeutic applications of growth hormone-releasing hormone agonists. Endocrinology. 160:1600–1612. 2019. View Article : Google Scholar : PubMed/NCBI
133	Munoz-Moreno L, Bajo AM, Prieto JC and Carmena MJ: Growth hormone-releasing hormone (GHRH) promotes metastatic phenotypes through EGFR/HER2 transactivation in prostate cancer cells. Mol Cell Endocrinol. 446:59–69. 2017. View Article : Google Scholar : PubMed/NCBI
134	Jimenez JJ, DelCanto GM, Popovics P, Perez A, Vila Granda A, Vidaurre I, Cai RZ, Rick FG, Swords RT and Schally AV: A new approach to the treatment of acute myeloid leukaemia targeting the receptor for growth hormone-releasing hormone. Br J Haematol. 181:476–485. 2018. View Article : Google Scholar : PubMed/NCBI
135	Chin YT, Wang LM, Hsieh MT, Shih YJ, Nana AW, Changou CA, Yang YSH, Chiu HC, Fu E, Davis PJ, et al: Leptin OB3 peptide suppresses leptin-induced signaling and progression in ovarian cancer cells. J Biomed Sci. 24:512017. View Article : Google Scholar : PubMed/NCBI
136	Zhang M, Zhang M, Wang J, Cai Q, Zhao R, Yu Y, Tai H, Zhang X and Xu C: Retro-inverso follicle-stimulating hormone peptide-mediated polyethylenimine complexes for targeted ovarian cancer gene therapy. Drug Deliv. 25:995–1003. 2018. View Article : Google Scholar : PubMed/NCBI
137	Sogaard CK, Moestue SA, Rye MB, Kim J, Nepal A, Liabakk NB, Bachke S, Bathen TF, Otterlei M and Hill DK: APIM-peptide targeting PCNA improves the efficacy of docetaxel treatment in the TRAMP mouse model of prostate cancer. Oncotarget. 9:11752–11766. 2018. View Article : Google Scholar : PubMed/NCBI
138	Farokhzad OC and Langer R: Impact of nanotechnology on drug delivery. ACS Nano. 3:16–20. 2009. View Article : Google Scholar : PubMed/NCBI
139	Liu X, Peng J, He J, Li Q, Zhou J, Liang X and Tang S: Selection and identification of novel peptides specifically targeting human cervical cancer. Amino Acids. 50:577–592. 2018. View Article : Google Scholar : PubMed/NCBI
140	Serrill JD, Wan X, Hau AM, Jang HS, Coleman DJ, Indra AK, Alani AW, McPhail KL and Ishmael JE: Coibamide A, a natural lariat depsipeptide, inhibits VEGFA/VEGFR2 expression and suppresses tumor growth in glioblastoma xenografts. Invest New Drugs. 34:24–40. 2016. View Article : Google Scholar
141	Chakrabarti S, Guha S and Majumder K: Food-derived bioac-tive peptides in human health: Challenges and opportunities. Nutrients. 10:17382018. View Article : Google Scholar
142	Sable R, Parajuli P and Jois S: Peptides, Peptidomimetics, and polypeptides from marine sources: A wealth of natural sources for pharmaceutical applications. Mar Drugs. 15:1242017. View Article : Google Scholar :
143	O'Brien-Simpson NM, Hoffmann R, Chia CSB and Wade JD: Editorial: Antimicrobial and Anticancer Peptides. Front Chem. 6:132018. View Article : Google Scholar : PubMed/NCBI
144	Sultan S, Huma N, Butt MS, Aleem M and Abbas M: Therapeutic potential of dairy bioactive peptides: A contemporary perspective. Crit Rev Food Sci Nutr. 58:105–115. 2018. View Article : Google Scholar
145	Felicio MR, Silva ON, Goncalves S, Santos NC and Franco OL: Peptides with dual antimicrobial and anticancer activities. Front Chem. 5:52017. View Article : Google Scholar : PubMed/NCBI
146	Mohanty DP, Mohapatra S, Misra S and Sahu PS: Milk derived bioactive peptides and their impact on human health-A review. Saudi J Biol Sci. 23:577–583. 2016. View Article : Google Scholar : PubMed/NCBI
147	Gonzalez-Montoya M, Hernandez-Ledesma B, Silvan JM, Mora-Escobedo R and Martinez-Villaluenga C: Peptides derived from in vitro gastrointestinal digestion of germinated soybean proteins inhibit human colon cancer cells proliferation and inflammation. Food Chem. 242:75–82. 2018. View Article : Google Scholar
148	Prateep A, Sumkhemthong S, Suksomtip M, Chanvorachote P and Chaotham C: Peptides extracted from edible mushroom: Lentinus squarrosulus induces apoptosis in human lung cancer cells. Pharm Biol. 55:1792–1799. 2017. View Article : Google Scholar : PubMed/NCBI
149	Newman DJ and Cragg GM: Natural products as sources of new drugs over the last 25 years. J Nat Prod. 70:461–477. 2007. View Article : Google Scholar : PubMed/NCBI
150	Fahs S, Patil-Sen Y and Snape TJ: Foldamers as anticancer therapeutics: Targeting protein-protein interactions and the cell membrane. Chembiochem. 16:1840–1853. 2015. View Article : Google Scholar : PubMed/NCBI
151	Dhar A, Mallick S, Ghosh P, Maiti A, Ahmed I, Bhattacharya S, Mandal T, Manna A, Roy K, Singh S, et al: Simultaneous inhibition of key growth pathways in melanoma cells and tumor regression by a designed bidentate constrained helical peptide. Biopolymers. 102:344–358. 2014. View Article : Google Scholar : PubMed/NCBI
152	Tanishiki N, Yano Y and Matsuzaki K: Endowment of pH responsivity to anticancer peptides by introducing 2,3-diami-nopropionic acid residues. Chembiochem. 20:2109–2117. 2019. View Article : Google Scholar : PubMed/NCBI
153	Dennison SR, Harris F, Mura M and Phoenix DA: An atlas of anionic antimicrobial peptides from amphibians. Curr Protein Pept Sci. 19:823–838. 2018. View Article : Google Scholar : PubMed/NCBI
154	Khamessi O, Ben Mabrouk H, ElFessi-Magouri R and Kharrat R: RK1, the first very short peptide from Buthus occi-tanus tunetanus inhibits tumor cell migration, proliferation and angiogenesis. Biochem Biophys Res Commun. 499:1–7. 2018. View Article : Google Scholar : PubMed/NCBI
155	Choi YJ, Park SJ, Park YS, Park HS, Yang KM and Heo K: EpCAM peptide-primed dendritic cell vaccination confers significant anti-tumor immunity in hepatocellular carcinoma cells. PLoS One. 13:e01906382018. View Article : Google Scholar : PubMed/NCBI
156	Matsueda S, Itoh K and Shichijo S: Antitumor activity of antibody against cytotoxic T lymphocyte epitope peptide of lymphocyte-specific protein tyrosine kinase. Cancer Sci. 109:611–617. 2018. View Article : Google Scholar : PubMed/NCBI
157	Peng X, Zhou C, Hou X, Liu Y, Wang Z, Peng X, Zhang Z, Wang R and Kong D: Molecular characterization and bioactivity evaluation of two novel bombinin peptides from the skin secretion of Oriental fire-bellied toad, Bombina orientalis. Amino Acids. 50:241–253. 2018. View Article : Google Scholar
158	Xie X, Zhou W, Hu Y, Chen Y, Zhang H and Li Y: A dual-function epidermal growth factor receptor pathway substrate 8 (Eps8)-derived peptide exhibits a potent cytotoxic T lymphocyte-activating effect and a specific inhibitory activity. Cell Death Dis. 9:3792018. View Article : Google Scholar : PubMed/NCBI
159	Wu ZZ, Ding GF, Huang FF, Yang ZS, Yu FM, Tang YP, Jia YL, Zheng YY and Chen R: Anticancer activity of anthopleura anjunae oligopeptides in prostate cancer DU-145 cells. Mar Drugs. 16:pii: E125. 2018. View Article : Google Scholar
160	Shen Y, Maupetit J, Derreumaux P and Tuffery P: Improved PEP-FOLD approach for peptide and miniprotein structure prediction. J Chem Theory Comput. 10:4745–4758. 2014. View Article : Google Scholar
161	Thevenet P, Shen Y, Maupetit J, Guyon F, Derreumaux P and Tuffery P: PEP-FOLD: An updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides. Nucleic Acids Res. 40:W288–W293. 2012. View Article : Google Scholar : PubMed/NCBI
162	Hao Y, Yang N, Teng D, Wang X, Mao R and Wang J: A review of the design and modification of lactoferricins and their derivatives. Biometals. 31:331–341. 2018. View Article : Google Scholar : PubMed/NCBI
163	Dathe M, Schumann M, Wieprecht T, Winkler A, Beyermann M, Krause E, Matsuzaki K, Murase O and Bienert M: Peptide helicity and membrane surface charge modulate the balance of electrostatic and hydrophobic interactions with lipid bilayers and biological membranes. Biochemistry. 35:12612–12622. 1996. View Article : Google Scholar : PubMed/NCBI
164	Sun S, Zhao G, Huang Y, Cai M, Yan Q, Wang H and Chen Y: Enantiomeric effect of d-Amino acid substitution on the mechanism of action of α-helical membrane-active peptides. Int J Mol Sci. 19:672017. View Article : Google Scholar
165	Hicks RP: Antibacterial and anticancer activity of a series of novel peptides incorporating cyclic tetra-substituted C(α) amino acids. Bioorg Med Chem. 24:4056–4065. 2016. View Article : Google Scholar : PubMed/NCBI
166	Zhou J, Yang X, Zhang W, Wang J, Wei C, Gu F, Lei T and Qin Y: Construction of an Anticancer Fusion Peptide (ACFP) derived from milk proteins and an assay of anti-ovarian cancer cells in vitro. Anticancer Agents Med Chem. 17:635–643. 2017. View Article : Google Scholar
167	Bracci L, Mandarini E, Brunetti J, Depau L, Pini A, Terzuoli L, Scali S and Falciani C: The GAG-specific branched peptide NT4 reduces angiogenesis and invasiveness of tumor cells. PLoS One. 13:e01947442018. View Article : Google Scholar : PubMed/NCBI
168	Chu HL, Yip BS, Chen KH, Yu HY, Chih YH, Cheng HT, Chou YT and Cheng JW: Novel antimicrobial peptides with high anticancer activity and selectivity. PLoS One. 10:e01263902015. View Article : Google Scholar : PubMed/NCBI
169	He B, Yang D, Qin M, Zhang Y, He B, Dai W, Wang X, Zhang Q, Zhang H and Yin C: Increased cellular uptake of peptide-modified PEGylated gold nanoparticles. Biochem Biophys Res Commun. 494:339–345. 2017. View Article : Google Scholar : PubMed/NCBI
170	Tsuchiya N, Hosono A, Yoshikawa T, Shoda K, Nosaka K, Shimomura M, Hara J, Nitani C, Manabe A, Yoshihara H, et al: Phase I study of glypican-3-derived peptide vaccine therapy for patients with refractory pediatric solid tumors. Oncoimmunology. 7:e13778722017. View Article : Google Scholar
171	Liang AL, Qian HL, Zhang TT, Zhou N, Wang HJ, Men XT, Qi W, Zhang PP, Fu M, Liang X, et al: Bifunctional fused polypeptide inhibits the growth and metastasis of breast cancer. Drug Des Devel Ther. 9:5671–5686. 2015.PubMed/NCBI
172	Herbert KJ, Ashton TM, Prevo R, Pirovano G and Higgins GS: T-LAK cell-originated protein kinase (TOPK): An emerging target for cancer-specific therapeutics. Cell Death Dis. 9:10892018. View Article : Google Scholar : PubMed/NCBI
173	Wu D, Gao Y, Qi Y, Chen L, Ma Y and Li Y: Peptide-based cancer therapy: Opportunity and challenge. Cancer Lett. 351:13–22. 2014. View Article : Google Scholar : PubMed/NCBI
174	Zachos I, Konstantinopoulos PA, Tzortzis V, Gravas S, Karatzas A, Karamouzis MV, Melekos M and Papavassiliou AG: Systemic therapy of metastatic bladder cancer in the molecular era: Current status and future promise. Expert Opin Investig Drugs. 19:875–887. 2010. View Article : Google Scholar : PubMed/NCBI
175	Amir E, Hughes S, Blackhall F, Thatcher N, Ostoros G, Timar J, Tovari J, Kovacs G and Dome B: Targeting blood vessels for the treatment of non-small cell lung cancer. Curr Cancer Drug Targets. 8:392–403. 2008. View Article : Google Scholar : PubMed/NCBI
176	Kim-Schulze S, Taback B and Kaufman HL: Cytokine therapy for cancer. Surg Oncol Clin N Am. 16:793–818. viii2007. View Article : Google Scholar : PubMed/NCBI
177	Niu F, Yan J, Ma B, Li S, Shao Y, He P, Zhang W, He W, Ma PX and Lu W: Lanthanide-doped nanoparticles conjugated with an anti-CD33 antibody and a p53-activating peptide for acute myeloid leukemia therapy. Biomaterials. 167:132–142. 2018. View Article : Google Scholar : PubMed/NCBI
178	Vats K, Sharma R, Sarma HD, Satpati D and Dash A: ⁶⁸Ga-labeled HBED-CC variant of uPAR targeting peptide AE105 compared with 68Ga-NODAGA-AE105. Anticancer Agents Med Chem. 18:1289–1294. 2018. View Article : Google Scholar
179	Ahmadpour S, Noaparast Z, Abedi SM and Hosseinimehr SJ: 99mTc-(tricine)-HYNIC-Lys-FROP peptide for breast tumor targeting. Anticancer Agents Med Chem. 18:1295–1302. 2018. View Article : Google Scholar
180	Zhang J, Spring H and Schwab M: Neuroblastoma tumor cell-binding peptides identified through random peptide phage display. Cancer Lett. 171:153–164. 2001. View Article : Google Scholar : PubMed/NCBI
181	Soudy R, Etayash H, Bahadorani K, Lavasanifar A and Kaur K: Breast cancer targeting peptide binds keratin 1: A new molecular marker for targeted drug delivery to breast cancer. Mol Pharm. 14:593–604. 2017. View Article : Google Scholar : PubMed/NCBI
182	Du Y, Wang L, Wang W, Guo T, Zhang M, Zhang P, Zhang Y, Wu K, Li A, Wang X, et al: Novel application of cell penetrating R11 peptide for diagnosis of bladder cancer. J Biomed Nanotechnol. 14:161–167. 2018. View Article : Google Scholar : PubMed/NCBI
183	Sato S, Nakamura T, Katagiri T, Tsuchikawa T, Kushibiki T, Hontani K, Takahashi M, Inoko K, Takano H, Abe H, et al: Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adeno-carcinoma cell proliferation. Oncotarget. 8:113662–113672. 2017. View Article : Google Scholar
184	Kang T, Huang Y, Zhu Q, Cheng H, Pei Y, Feng J, Xu M, Jiang G, Song Q, Jiang T, et al: Necroptotic cancer cells-mimicry nanovaccine boosts anti-tumor immunity with tailored immune-stimulatory modality. Biomaterials. 164:80–97. 2018. View Article : Google Scholar : PubMed/NCBI
185	Garay H, Espinosa LA, Perera Y, Sanchez A, Diago D, Perea SE, Besada V, Reyes O and Gonzalez LJ: Characterization of low-abundance species in the active pharmaceutical ingredient of CIGB-300: A clinical-grade anticancer synthetic peptide. J Pept Sci. 24:e30812018. View Article : Google Scholar : PubMed/NCBI
186	Perea SE, Reyes O, Baladron I, Perera Y, Farina H, Gil J, Rodriguez A, Bacardi D, Marcelo JL, Cosme K, et al: CIGB-300, a novel proapoptotic peptide that impairs the CK2 phosphorylation and exhibits anticancer properties both in vitro and in vivo. Mol Cell Biochem. 316:163–167. 2008. View Article : Google Scholar : PubMed/NCBI
187	Rodriguez-Ulloa A, Ramos Y, Gil J, Perera Y, Castellanos-Serra L, Garcia Y, Betancourt L, Besada V, Gonzalez LJ, Fernandez-de-Cossio J, et al: Proteomic profile regulated by the anticancer peptide CIGB-300 in non-small cell lung cancer (NSCLC) cells. J Proteome Res. 9:5473–5483. 2010. View Article : Google Scholar : PubMed/NCBI
188	Hirabayashi K, Yanagisawa R, Saito S, Higuchi Y, Koya T, Sano K, Koido S, Okamoto M, Sugiyama H, Nakazawa Y, et al: Feasibility and immune response of WT1 peptide vaccination in combination with OK-432 for paediatric solid tumors. Anticancer Res. 38:2227–2234. 2018.PubMed/NCBI
189	Yanagisawa R, Koizumi T, Koya T, Sano K, Koido S, Nagai K, Kobayashi M, Okamoto M, Sugiyama H and Shimodaira S: WT1-pulsed dendritic cell vaccine combined with chemotherapy for resected pancreatic cancer in a phase I study. Anticancer Res. 38:2217–2225. 2018.PubMed/NCBI
190	Ohno S, Takano F, Ohta Y, Kyo S, Myojo S, Dohi S, Sugiyama H, Ohta T and Inoue M: Frequency of myeloid dendritic cells can predict the efficacy of Wilms' tumor 1 peptide vaccination. Anticancer Res. 31:2447–2452. 2011.PubMed/NCBI
191	Ohno S, Kyo S, Myojo S, Dohi S, Ishizaki J, Miyamoto K, Morita S, Sakamoto J, Enomoto T, Kimura T, et al: Wilms' tumor 1 (WT1) peptide immunotherapy for gynecological malignancy. Anticancer Res. 29:4779–4784. 2009.PubMed/NCBI
192	Ishikawa H, Imano M, Shiraishi O, Yasuda A, Peng YF, Shinkai M, Yasuda T, Imamoto H and Shiozaki H: Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer. Gastric Cancer. 17:173–180. 2014. View Article : Google Scholar
193	Vasef MA, Ross JS and Cohen MB: Telomerase activity in human solid tumors. Diagnostic utility and clinical applications. Am J Clin Pathol. 112(1 Suppl): S68–S75. 1999.PubMed/NCBI
194	Bernhardt SL, Gjertsen MK, Trachsel S, Moller M, Eriksen JA, Meo M, Buanes T and Gaudernack G: Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: A dose escalating phase I/II study. Br J Cancer. 95:1474–1482. 2006. View Article : Google Scholar : PubMed/NCBI
195	Kokhaei P, Palma M, Hansson L, Osterborg A, Mellstedt H and Choudhury A: Telomerase (hTERT 611-626) serves as a tumor antigen in B-cell chronic lymphocytic leukemia and generates spontaneously antileukemic, cytotoxic T cells. Exp Hematol. 35:297–304. 2007. View Article : Google Scholar : PubMed/NCBI
196	Aspeslagh S, Awada A, Matos-Pita A, Aftimos P, Bahleda R, Varga A and Soria JC: Phase I dose-escalation study of plitidepsin in combination with bevacizumab in patients with refractory solid tumors. Anticancer Drugs. 27:1021–1027. 2016. View Article : Google Scholar : PubMed/NCBI
197	Engel JB, Tinneberg HR, Rick FG, Berkes E and Schally AV: Targeting of peptide cytotoxins to LHRH receptors for treatment of cancer. Curr Drug Targets. 17:488–494. 2016. View Article : Google Scholar : PubMed/NCBI
198	Noguchi M, Matsumoto K, Uemura H, Arai G, Eto M, Naito S, Ohyama C, Nasu Y, Tanaka M, Moriya F, et al: An open-label, randomized phase II trial of personalized peptide vaccination in patients with bladder cancer that progressed after platinum-based chemotherapy. Clin Cancer Res. 22:54–60. 2016. View Article : Google Scholar
199	Toh U, Saku S, Okabe M, Iwakuma N, Kimitsuki Y, Akashi M, Ogo E, Yamada A, Shichijo S, Itoh K, et al: Development of peptide vaccines for triple-negative breast cancer treatment. Gan To Kagaku Ryoho. 43:1249–1251. 2016.In Japanese. PubMed/NCBI
200	Brown TA, Byrd K, Vreeland TJ, Clifton GT, Jackson DO, Hale DF, Herbert GS, Myers JW, Greene JM, Berry JS, et al: Final analysis of a phase I/IIa trial of the folate-binding protein-derived E39 peptide vaccine to prevent recurrence in ovarian and endometrial cancer patients. Cancer Med. 8:4678–4687. 2019. View Article : Google Scholar : PubMed/NCBI
201	Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, Gailani F, Riley L, Conlon K, Pockaj B, et al: gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 364:2119–2127. 2011. View Article : Google Scholar : PubMed/NCBI
202	Mikecin AM, Walker LR, Kuna M and Raucher D: Thermally targeted p21 peptide enhances bortezomib cytotoxicity in androgen-independent prostate cancer cell lines. Anticancer Drugs. 25:189–199. 2014. View Article : Google Scholar
203	Korani M, Korani S, Zendehdel E, Nikpoor AR, Jaafari MR, Orafai HM, Johnston TP and Sahebkar A: Enhancing the therapeutic efficacy of bortezomib in cancer therapy using polymeric nanostructures. Curr Pharm Des. 25:4883–4892. 2019. View Article : Google Scholar : PubMed/NCBI
204	Zhou Y, Liu X, Xue J, Liu L, Liang T, Li W, Yang X, Hou X and Fang H: Discovery of peptide boronate derivatives as histone deacetylase and proteasome dual inhibitors for overcoming bortezomib resistance of multiple myeloma. J Med Chem. 63:4701–4715. 2020. View Article : Google Scholar : PubMed/NCBI
205	Garofalo M, Grazioso G, Cavalli A and Sgrignani J: How computational chemistry and drug delivery techniques can support the development of new anticancer drugs. Molecules. 25:17562020. View Article : Google Scholar :
206	Adlakha S, Sharma A, Vaghasiya K, Ray E and Verma RK: Inhalation delivery of host defence peptides (HDP) using nano-formulation strategies: A pragmatic approach for therapy of pulmonary ailments. Curr Protein Pept Sci. 21:369–378. 2020. View Article : Google Scholar
207	Tu Y, Tao J, Wang F, Liu P, Han Z, Li Z, Ma Y and Gu Y: A novel peptide targeting gastrin releasing peptide receptor for pancreatic neoplasm detection. Biomater Sci. 8:2682–2693. 2020. View Article : Google Scholar : PubMed/NCBI
208	Ohana J, Sandler U, Kass G, Stemmer SM and Devary Y: dTCApFs, a derivative of a novel human hormone peptide, induces apoptosis in cancer cells through a mechanism involving loss of Golgi function. Mol Clin Oncol. 7:991–999. 2017.PubMed/NCBI
209	Stemmer SM, Benjaminov O, Silverman MH, Sandler U, Purim O, Sender N, Meir C, Oren-Apoteker P, Ohana J and Devary Y: A phase I clinical trial of dTCApFs, a derivative of a novel human hormone peptide, for the treatment of advanced/metastatic solid tumors. Mol Clin Oncol. 8:22–29. 2018.PubMed/NCBI
210	Murali R and Kieber-Emmons T: Cancer immunotherapeutics: Evolution of monoclonal antibodies to peptide immunogens. Monoclon Antib Immunodiagn Immunother. 33:179–182. 2014. View Article : Google Scholar : PubMed/NCBI
211	Tan Z and Zhang S: Past, present, and future of targeting ras for cancer therapies. Mini Rev Med Chem. 16:345–357. 2016. View Article : Google Scholar
212	Li QX, Yu DH, Liu G, Ke N, McKelvy J and Wong-Staal F: Selective anticancer strategies via intervention of the death pathways relevant to cell transformation. Cell Death Differ. 15:1197–1210. 2008. View Article : Google Scholar : PubMed/NCBI
213	Micale N, Scarbaci K, Troiano V, Ettari R, Grasso S and Zappala M: Peptide-based proteasome inhibitors in anticancer drug design. Med Res Rev. 34:1001–1069. 2014. View Article : Google Scholar : PubMed/NCBI
214	Wang X, Chen X, Yang X, Gao W, He B, Dai W, Zhang H, Wang X, Wang J, Zhang X, et al: A nanomedicine based combination therapy based on QLPVM peptide functionalized liposomal tamoxifen and doxorubicin against Luminal A breast cancer. Nanomedicine. 12:387–397. 2016. View Article : Google Scholar
215	Cheng T and Zhan X: Pattern recognition for predictive, preventive, and personalized medicine in cancer. EPMA J. 8:51–60. 2017. View Article : Google Scholar : PubMed/NCBI
216	Vadevoo SMP, Gurung S, Khan F, Haque ME, Gunassekaran GR, Chi L, Permpoon U and Lee B: Peptide-based targeted therapeutics and apoptosis imaging probes for cancer therapy. Arch Pharm Res. 42:150–158. 2019. View Article : Google Scholar : PubMed/NCBI
217	Sun X, Li Y, Liu T, Li Z, Zhang X and Chen X: Peptide-based imaging agents for cancer detection. Adv Drug Deliv Rev. 110-111:38–51. 2017. View Article : Google Scholar :
218	Ehlerding EB, Sun L, Lan X, Zeng D and Cai W: Dual-targeted molecular imaging of cancer. J Nucl Med. 59:390–395. 2018. View Article : Google Scholar : PubMed/NCBI
219	Wang Q, Li SB, Zhao YY, Dai DN, Du H, Lin YZ, Ye JC, Zhao J, Xiao W, Mei Y, et al: Identification of a sodium pump Na(+)/K(+) ATPase alpha1-targeted peptide for PET imaging of breast cancer. J Control Release. 281:178–188. 2018. View Article : Google Scholar : PubMed/NCBI
220	Perez SA, von Hofe E, Kallinteris NL, Gritzapis AD, Peoples GE, Papamichail M and Baxevanis CN: A new era in anticancer peptide vaccines. Cancer. 116:2071–2080. 2010.PubMed/NCBI