|
1
|
Russell RC, Fang C and Guan KL: An
emerging role for TOR signaling in mammalian tissue and stem cell
physiology. Development. 138:3343–3356. 2011. View Article : Google Scholar
|
|
2
|
Laplante M and Sabatini DM: mTOR signaling
in growth control and disease. Cell. 149:274–293. 2012. View Article : Google Scholar
|
|
3
|
Saxton RA and Sabatini DM: mTOR signaling
in growth, metabolism, and disease. Cell. 168:960–976. 2017.
View Article : Google Scholar
|
|
4
|
Guertin DA and Sabatini DM: The
pharmacology of mTOR inhibition. Sci Signal. 2:pe242009. View Article : Google Scholar
|
|
5
|
Jacinto E, Loewith R, Schmidt A, Lin S,
Rüegg MA, Hall A and Hall MN: Mammalian TOR complex 2 controls the
actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol.
6:1122–1128. 2004. View
Article : Google Scholar
|
|
6
|
Loewith R, Jacinto E, Wullschleger S,
Lorberg A, Crespo JL, Bonenfant D, Oppliger W, Jenoe P and Hall MN:
Two TOR complexes, only one of which is rapamycin sensitive, have
distinct roles in cell growth control. Mol Cell. 10:457–468. 2002.
View Article : Google Scholar
|
|
7
|
Sabatini DM: mTOR and cancer: Insights
into a complex relationship. Nat Rev Cancer. 6:729–734. 2006.
View Article : Google Scholar
|
|
8
|
Volarević S and Thomas G: Role of S6
phosphorylation and S6 kinase in cell growth. Prog Nucleic Acid Res
Mol Biol. 65:101–127. 2001. View Article : Google Scholar
|
|
9
|
Sato T, Nakashima A, Guo L, Coffman K and
Tamanoi F: Single amino-acid changes that confer constitutive
activation of mTOR are discovered in human cancer. Oncogene.
29:2746–2752. 2010. View Article : Google Scholar
|
|
10
|
Musa J, Orth MF, Dallmayer M, Baldauf M,
Pardo C, Rotblat B, Kirchner T, Leprivier G and Grünewald TG:
Eukaryotic initiation factor 4E-binding protein 1 (4E-BP1): A
master regulator of mRNA translation involved in tumorigenesis.
Oncogene. 35:4675–4688. 2016. View Article : Google Scholar
|
|
11
|
Ganley IG, Lam du H, Wang J, Ding X, Chen
S and Jiang X: ULK1.ATG13.FIP200 complex mediates mTOR signaling
and is essential for autophagy. J Biol Chem. 284:12297–12305. 2009.
View Article : Google Scholar
|
|
12
|
Wiza C, Nascimento EB and Ouwens DM: Role
of PRAS40 in Akt and mTOR signaling in health and disease. Am J
Physiol Endocrinol Metab. 302:E1453–E1460. 2012. View Article : Google Scholar
|
|
13
|
Sarbassov DD, Ali SM, Kim DH, Guertin DA,
Latek RR, Erdjument-Bromage H, Tempst P and Sabatini DM: Rictor, a
novel binding partner of mTOR, defines a rapamycin-insensitive and
raptor-independent pathway that regulates the cytoskeleton. Curr
Biol. 14:1296–1302. 2004. View Article : Google Scholar
|
|
14
|
Gulati N, Karsy M, Albert L, Murali R and
Jhanwar-Uniyal M: Involvement of mTORC1 and mTORC2 in regulation of
glioblastoma multiforme growth and motility. Int J Oncol.
35:731–740. 2009.
|
|
15
|
Jhanwar-Uniyal M, Jeevan D, Neil J,
Shannon C, Albert L and Murali R: Deconstructing mTOR complexes in
regulation of Glioblastoma Multiforme and its stem cells. Adv Biol
Regul. 53:202–210. 2013. View Article : Google Scholar
|
|
16
|
Guertin DA and Sabatini DM: Defining the
role of mTOR in cancer. Cancer Cell. 12:9–22. 2007. View Article : Google Scholar
|
|
17
|
Ostrom QT, Cioffi G, Gittleman H, Patil N,
Waite K, Kruchko C and Barnholtz-Sloan JS: CBTRUS statistical
report: Primary brain and other central nervous system tumors
diagnosed in the United States in 2012-2016. Neuro Oncol. 21(Suppl
5): v1–v100. 2019. View Article : Google Scholar
|
|
18
|
Brennan C, Momota H, Hambardzumyan D,
Ozawa T, Tandon A, Pedraza A and Holland E: Glioblastoma subclasses
can be defined by activity among signal transduction pathways and
associated genomic alterations. PLoS One. 4:e77522009. View Article : Google Scholar
|
|
19
|
Cancer Genome Atlas Research Network:
Comprehensive genomic characterization defines human glioblastoma
genes and core pathways. Nature. 455:1061–1068. 2008. View Article : Google Scholar
|
|
20
|
Brennan CW, Verhaak RG, McKenna A, Campos
B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ,
Berman SH, et al: The somatic genomic landscape of glioblastoma.
Cell. 155:462–477. 2013. View Article : Google Scholar
|
|
21
|
Jhanwar-Uniyal M, Labagnara M, Friedman M,
Kwasnicki A and Murali R: Glioblastoma: Molecular pathways, stem
cells and therapeutic targets. Cancers (Basel). 7:538–555. 2015.
View Article : Google Scholar
|
|
22
|
Jhanwar-Uniyal M, Albert L, McKenna E,
Karsy M, Rajdev P, Braun A and Murali R: Deciphering the signaling
pathways of cancer stem cells of glioblastoma multiforme: Role of
Akt/mTOR and MAPK pathways. Adv Enzyme Regul. 51:164–170. 2011.
View Article : Google Scholar
|
|
23
|
Jhanwar-Uniyal M, Wainwright JV, Mohan AL,
Tobias ME, Murali R, Gandhi CD and Schmidt MH: Diverse signaling
mechanisms of mTOR complexes: mTORC1 and mTORC2 in forming a
formidable relationship. Adv Biol Regul. 72:51–62. 2019. View Article : Google Scholar
|
|
24
|
Chiu MI, Katz H and Berlin V: RAPT1, a
mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin
complex. Proc Natl Acad Sci USA. 91:12574–12578. 1994. View Article : Google Scholar
|
|
25
|
Albert L, Karsy M, Murali R and
Jhanwar-Uniyal M: Inhibition of mTOR activates the MAPK pathway in
glioblastoma multiforme. Cancer Genomics Proteomics. 6:255–261.
2009.
|
|
26
|
Feldman ME, Apsel B, Uotila A, Loewith R,
Knight ZA, Ruggero D and Shokat KM: Active-site inhibitors of mTOR
target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol.
7:e382009. View Article : Google Scholar
|
|
27
|
Thoreen CC, Kang SA, Chang JW, Liu Q,
Zhang J, Gao Y, Reichling LJ, Sim T, Sabatini DM and Gray NS: An
ATP-competitive mammalian target of rapamycin inhibitor reveals
rapamycin-resistant functions of mTORC1. J Biol Chem.
284:8023–8032. 2009. View Article : Google Scholar
|
|
28
|
Liu Q, Chang JW, Wang J, Kang SA, Thoreen
CC, Markhard A, Hur W, Zhang J, Sim T, Sabatini DM and Gray NS:
Discovery of 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)
phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one as a
highly potent, selective mammalian target of rapamycin (mTOR)
inhibitor for the treatment of cancer. J Med Chem. 53:7146–7155.
2010. View Article : Google Scholar
|
|
29
|
Liu Q, Kang SA, Thoreen CC, Hur W, Wang J,
Chang JW, Markhard A, Zhang J, Sim T, Sabatini DM and Gray NS:
Development of ATP-competitive mTOR inhibitors. Methods Mol Biol.
821:447–460. 2012. View Article : Google Scholar
|
|
30
|
Liu Q, Wang J, Kang SA, Thoreen CC, Hur W,
Ahmed T, Sabatini DM and Gray NS: Discovery of
9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one
(Torin2) as a potent, selective, and orally available mammalian
target of rapamycin (mTOR) inhibitor for treatment of cancer. J Med
Chem. 54:1473–1480. 2011. View Article : Google Scholar
|
|
31
|
Takeuchi CS, Kim BG, Blazey CM, Ma S,
Johnson HW, Anand NK, Arcalas A, Baik TG, Buhr CA, Cannoy J, et al:
Discovery of a novel class of highly potent, selective,
ATP-competitive, and orally bioavailable inhibitors of the
mammalian target of rapamycin (mTOR). J Med Chem. 56:2218–2234.
2013. View Article : Google Scholar
|
|
32
|
Sokolosky ML, Stadelman KM, Chappell WH,
Abrams SL, Martelli AM, Stivala F, Libra M, Nicoletti F, Drobot LB,
Franklin RA, et al: Involvement of Akt-1 and mTOR in sensitivity of
breast cancer to targeted therapy. Oncotarget. 2:538–550. 2011.
View Article : Google Scholar
|
|
33
|
Sarkaria JN, Galanis E, Wu W, Peller PJ,
Giannini C, Brown PD, Uhm JH, McGraw S, Jaeckle KA and Buckner JC:
North Central Cancer Treatment Group Phase I trial N057K of
everolimus (RAD001) and temozolomide in combination with radiation
therapy in patients with newly diagnosed glioblastoma multiforme.
Int J Radiat Oncol Biol Phys. 81:468–475. 2011. View Article : Google Scholar
|
|
34
|
Hainsworth JD, Shih KC, Shepard GC,
Tillinghast GW, Brinker BT and Spigel DR: Phase II study of
concurrent radiation therapy, temozolomide, and bevacizumab
followed by bevacizumab/everolimus as first-line treatment for
patients with glioblastoma. Clin Adv Hematol Oncol. 10:240–246.
2012.
|
|
35
|
Galanis E, Buckner JC, Maurer MJ,
Kreisberg JI, Ballman K, Boni J, Peralba JM, Jenkins RB, Dakhil SR,
Morton RF, et al: Phase II trial of temsirolimus (CCI-779) in
recurrent glioblastoma multiforme: A North Central Cancer Treatment
Group Study. J Clin Oncol. 23:5294–5304. 2005. View Article : Google Scholar
|
|
36
|
Cloughesy TF, Yoshimoto K, Nghiemphu P,
Brown K, Dang J, Zhu S, Hsueh T, Chen Y, Wang W, Youngkin D, et al:
Antitumor activity of rapamycin in a Phase I trial for patients
with recurrent PTEN-deficient glioblastoma. PLoS Med. 5:e82008.
View Article : Google Scholar
|
|
37
|
Takano A, Usui I, Haruta T, Kawahara J,
Uno T, Iwata M and Kobayashi M: Mammalian target of rapamycin
pathway regulates insulin signaling via subcellular redistribution
of insulin receptor substrate 1 and integrates nutritional signals
and metabolic signals of insulin. Mol Cell Biol. 21:5050–5062.
2001. View Article : Google Scholar
|
|
38
|
Sancak Y, Thoreen CC, Peterson TR,
Lindquist RA, Kang SA, Spooner E, Carr SA and Sabatini DM: PRAS40
is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol
Cell. 25:903–915. 2007. View Article : Google Scholar
|
|
39
|
Kovacina KS, Park GY, Bae SS, Guzzetta AW,
Schaefer E, Birnbaum MJ and Roth RA: Identification of a
proline-rich Akt substrate as a 14-3-3 binding partner. J Biol
Chem. 278:10189–10194. 2003. View Article : Google Scholar
|
|
40
|
Laplante M and Sabatini DM: mTOR
signaling. Cold Spring Harb Perspect Biol. 4:a0115932012.
View Article : Google Scholar
|
|
41
|
Jhanwar-Uniyal M, Gillick JL, Neil J,
Tobias M, Thwing ZE and Murali R: Distinct signaling mechanisms of
mTORC1 and mTORC2 in glioblastoma multiforme: A tale of two
complexes. Adv Biol Regul. 57:64–74. 2015. View Article : Google Scholar
|
|
42
|
Rodrik-Outmezguine VS, Okaniwa M, Yao Z,
Novotny CJ, McWhirter C, Banaji A, Won H, Wong W, Berger M, de
Stanchina E, et al: Overcoming mTOR resistance mutations with a
new-generation mTOR inhibitor. Nature. 534:272–276. 2016.
View Article : Google Scholar
|
|
43
|
Fan Q, Aksoy O, Wong RA, Ilkhanizadeh S,
Novotny CJ, Gustafson WC, Truong AY, Cayanan G, Simonds EF,
Haas-Kogan D, et al: A kinase inhibitor targeted to mTORC1 drives
regression in glioblastoma. Cancer Cell. 31:424–435. 2017.
View Article : Google Scholar
|
|
44
|
Jhanwar-Uniyal M: Mighty RapaLink-1
vanquishes undruggable mutant mTOR in glioblastoma. Transl Cancer
Res. 6(Suppl 7): S1143–S1148. 2017. View Article : Google Scholar
|
|
45
|
Liu Q, Xu C, Kirubakaran S, Zhang X, Hur
W, Liu Y, Kwiatkowski NP, Wang J, Westover KD, Gao P, et al:
Characterization of Torin2, an ATP-competitive inhibitor of mTOR,
ATM, and ATR. Cancer Res. 73:2574–2586. 2013. View Article : Google Scholar
|
|
46
|
Watanabe T, Sato A, Kobayashi-Watanabe N,
Sueoka-Aragane N, Kimura S and Sueoka E: Torin2 potentiates
anticancer effects on adult T-cell leukemia/lymphoma by inhibiting
mammalian target of rapamycin. Anticancer Res. 36:95–102. 2016.
|
|
47
|
Sadowski SM, Boufraqech M, Zhang L, Mehta
A, Kapur P, Zhang Y, Li Z, Shen M and Kebebew E: Torin2 targets
dysregulated pathways in anaplastic thyroid cancer and inhibits
tumor growth and metastasis. Oncotarget. 6:18038–18049. 2015.
View Article : Google Scholar
|
|
48
|
Chopra SS, Jenney A, Palmer A, Niepel M,
Chung M, Mills C, Sivakumaren SC, Liu Q, Chen JY, Yapp C, et al:
Torin2 exploits replication and checkpoint vulnerabilities to cause
death of PI3K-activated triple-negative breast cancer cells. Cell
Syst. 10:66–81.e11. 2020. View Article : Google Scholar
|
|
49
|
Luo J, Pi G, Xiao H, Ye Y, Li Q, Zhao L,
Huang H, Luo H, Zhang Q, Wang D and Wang G: Torin2 enhances the
radiosensitivity of MCF-7 breast cancer cells by downregulating the
mTOR signaling pathway and ATM phosphorylation. Mol Med Rep.
17:366–373. 2018.
|
|
50
|
Zhu YR, Zhou XZ, Zhu LQ, Yao C, Fang JF,
Zhou F, Deng XW and Zhang YQ: The anti-cancer activity of the
mTORC1/2 dual inhibitor XL388 in preclinical osteosarcoma models.
Oncotarget. 7:49527–49538. 2016. View Article : Google Scholar
|
|
51
|
Xiong Z, Zang Y, Zhong S, Zou L, Wu Y, Liu
S, Fang Z, Shen Z, Ding Q and Chen S: The preclinical assessment of
XL388, a mTOR kinase inhibitor, as a promising anti-renal cell
carcinoma agent. Oncotarget. 8:30151–30161. 2017. View Article : Google Scholar
|
