Combined SFK/mTOR inhibition prevents rapamycin-Induced Feedback Activation of AKT and Elicits Efficient Tumor Regression

Cancer Research

Volumn 74, Issue 17, 2014, Pages 4762-4771

  Yori, Jennifer L ^a   Lozada, Kristen L ^a   Seachrist, Darcie D ^a   Mosley, Jonathan D ^b   Abdul Karim, Fadi W ^c   Booth, Christine N ^c   Flask, Chris A ^a,d   Keri, Ruth A ^a  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c LERNER RESEARCH INSTITUTE   (United States)

^d CASE WESTERN RESERVE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABELSON KINASE; DASATINIB; MTOR PROTEIN, HUMAN; PROTEIN KINASE B; PYRIMIDINE DERIVATIVE; RAPAMYCIN; TARGET OF RAPAMYCIN KINASE; THIAZOLE DERIVATIVE;

ANIMAL; ANTAGONISTS AND INHIBITORS; BREAST TUMOR; DRUG EFFECTS; DRUG RESISTANCE; FEMALE; GENETICS; HUMAN; MCF 7 CELL LINE; MOUSE; ONCOGENE SRC; PATHOLOGY; PHOSPHORYLATION; RAT; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ANIMALS; BREAST NEOPLASMS; CELL LINE, TUMOR; DASATINIB; DRUG RESISTANCE, NEOPLASM; FEMALE; GENES, SRC; HUMANS; MCF-7 CELLS; MICE; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-ABL; PROTO-ONCOGENE PROTEINS C-AKT; PYRIMIDINES; RATS; SIGNAL TRANSDUCTION; SIROLIMUS; THIAZOLES; TOR SERINE-THREONINE KINASES;

EID: 84907060513     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-13-3627     Document Type: Article

References (51)

1. Baselga J. Targeting the phosphoinositide-3 (PI3) kinase pathway in breast cancer. Oncologist 2011;16:12-9.
2. Wilson TR, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, et al. Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature 2012;487:505-9.
3. Logue JS, Morrison DK. Complexity in the signaling network: insights from the use of targeted inhibitors in cancer therapy. Genes Dev 2012;26:641-50.
4. Inoki K, Li Y, Zhu T, Wu J, Guan KL. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 2002;4:648-57.
5. Zaytseva YY, Valentino JD, Gulhati P, Evers BM. mTOR inhibitors in cancer therapy. Cancer Lett 2012;319:1-7.
6. Manning BD. Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. J Cell Biol 2004;167:399-403.
7. Dibble CC, Asara JM, Manning BD. Characterization of Rictor phos-phorylation sites reveals direct regulation of mTOR complex 2 by S6K1. Mol Cell Biol 2009;29:5657-70.
8. Rodrik-Outmezguine VS, Chandarlapaty S, Pagano NC, Poulikakos PI, Scaltriti M, Moskatel E, et al. mTOR kinase inhibition causes feedback-dependent biphasic regulation of AKT signaling. Cancer Discov 2011;1:248-59.
9. Serra V, Scaltriti M, Prudkin L, Eichhorn PJ, Ibrahim YH, Chandarlapaty S, et al. PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer. Oncogene 2011;30:2547-57.
10. Vojtechova M, Tureckova J, Kucerova D, Sloncova E, Vachtenheim J, Tuhackova Z. Regulation of mTORC1 signaling by Src kinase activity is Akt1-independent in RSV-transformed cells. Neoplasia 2008;10: 99-107.
11. Di Florio A, Adesso L, Pedrotti S, Capurso G, Pilozzi E, Corbo V, et al. Src kinase activity coordinates cell adhesion and spreading with activation of mammalian target of rapamycin in pancreatic endocrine tumour cells. Endocr Relat Cancer 2011;18:541-54.
12. Park BJ, Whichard ZL, Corey SJ. Dasatinib synergizes with both cytotoxic and signal transduction inhibitors in heterogeneous breast cancer cell lines-lessons for design of combination targeted therapy. Cancer Lett 2012;320:104-10.
13. Castoria G, Migliaccio A, Bilancio A, Di Domenico M, de Falco A, Lombardi M, et al. PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells. EMBO J 2001; 20:6050-9.
14. Zhang XH, Wang Q, Gerald W, Hudis CA, Norton L, Smid M, et al. Latent bone metastasis in breast cancertied to Src-dependent survival signals. Cancer Cell 2009;16:67-78.
15. Finn RS. Targeting Src in breast cancer. Ann Oncol 2008;19:1379-86.
16. Caron E, Ghosh S, Matsuoka Y, Ashton-Beaucage D, Therrien M, Lemieux S, et al. A comprehensive map of the mTOR signaling network. Mol Syst Biol 2010;6:453.
17. Jiang T, Qiu Y. Interaction between Src and a C-terminal proline-rich motif of Akt is required for Akt activation. J Biol Chem 2003;278: 15789-93.
18. Rebholz H, Panasyuk G, Fenton T, Nemazanyy I, Valovka T, Flajolet M, et al. Receptor association and tyrosine phosphorylation of S6 kinases. FEBS J 2006;273:2023-36.
19. Mayer EL, Baurain JF, Sparano J, Strauss L, Campone M, Fumoleau P, et al. A phase 2 trial of dasatinib in patients with advanced HER2-positive and/or hormone receptor-positive breast cancer. Clin Cancer Res 2011;17:6897-904.
20. Finn RS, Bengala C, Ibrahim N, Roche H, Sparano J, Strauss LC, et al. Dasatinib as a single agent in triple-negative breast cancer: results of an open-label phase 2 study. Clin Cancer Res 2011;17:6905-13.
21. Anbalagan M, Moroz K, Ali A, Carrier L, Glodowski S, Rowan BG. Subcellular localization of total and activated Src kinase in African American and Caucasian breast cancer. PLoS ONE 2012;7:e33017.
22. Miller T, Rexer B, Garrett J, Arteaga C. Mutations in the phosphatidy-linositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res 2011;13:224.
23. Noh WC, Mondesire WH, Peng J, Jian W, Zhang H, Dong J, et al. Determinants of rapamycin sensitivity in breast cancer cells. Clin Cancer Res 2004;10:1013-23.
24. Pichot CS, Hartig SM, Xia L, Arvanitis C, Monisvais D, Lee FY, et al. Dasatinib synergizes with doxorubicin to block growth, migration, and invasion of breast cancer cells. Br J Cancer 2009;101:38-47.
25. Tryfonopoulos D, Walsh S, Collins DM, Flanagan L, Quinn C, Corkery B, et al. Src: a potential target forthe treatment of triple-negative breast cancer. Ann Oncol 2011;22:2234-40.
26. Green TP, Fennell M, Whittaker R, Curwen J, Jacobs V, Allen J, et al. Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530. Mol Oncol 2009;3:248-61.
27. Johnson E, Seachrist DD, DeLeon-Rodriguez CM, Lozada KL, Miedler J, Abdul-Karim FW, et al. HER2/ErbB2-induced breast cancer cel migration and invasion require p120 catenin activation of Rac1 and Cdc42. J Biol Chem 2010;285:29491-501.
28. Yori JL, Johnson E, Zhou G, Jain MK, Keri RA. Kruppel-like factor 4 inhibits epithelial-to-mesenchymal transition through regulation of E-cadherin gene expression. J Biol Chem 2010;285:16854-63.
29. Mosley JD, Poirier JT, Seachrist DD, Landis MD, Keri RA. Rapamycin inhibits multiple stages of c-Neu/ErbB2 induced tumor progression in a transgenic mouse model of HER2-positive breast cancer. Mol Cancer Ther 2007;6:2188-97.
30. Luo FR, Yang Z, Camuso A, Smykla R, McGlinchey K, Fager K, et al. Dasatinib (BMS-354825) pharmacokinetics and pharmacodynamic biomarkers in animal models predict optimal clinical exposure. 2006;12:7180-6.
31. Messina MP, Rauktys A, Lee L, Dabora SL. Tuberous sclerosis preclinical studies: timing of treatment, combination of a rapamycin analog (CCI-779) and interferon-gamma, and comparison of rapamycin to CCI-779. BMC Pharmacol 2007;7:14.
32. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.
33. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006;66:1500-8.
34. Chaturvedi D, Gao X, Cohen MS, Taunton J, Patel TB. Rapamycin induces transactivation of the EGFR and increases cell survival. Oncogene 2009;28:1187-96.
35. Guy CT, Cardiff RD, Muller WJ. Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol Cell Biol 1992;12:954-61.
36. Morton JP, Karim SA, Graham K, Timpson P, Jamieson N, Athineos D, et al. Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinoma. Gastroenterology 2010;139:292-303.
37. Chan CM, Jing X, Pike LA, Zhou Q, Lim D-J, Sams SB, et al. Targeted inhibitionofSrckinasewith dasatinib blocks thyroid cancergrowthand metastasis. Clin Cancer Res 2012;18:3580-91.
38. Pool SE, Bison S, Koelewijn SJ, van der Graaf LM, Melis M, Krenning EP, et al. mTOR inhibitor RAD001 promotes metastasis in a rat model of pancreatic neuroendocrine cancer. Cancer Res 2013;73:12-8.
39. Gokmen-Polar Y, Liu Y, Toroni RA, Sanders KL, Mehta R, Badve S, et al. Investigational drug MLN0128, a novel TORC1/2 inhibitor, demonstrates potent oral antitumor activity in human breast cancer xenograft models. Breast Cancer Res Treat 2012;136:673-82.
40. Summy JM, Gallick GE. Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev 2003;22:337-58.
41. Kurebayashi J, Kanomata N, Moriya T, Kozuka Y, Watanabe M, Sonoo H. Preferential antitumor effect of the Src inhibitor dasatinib associated with a decreased proportion of aldehyde dehydrogenase 1-positive cells in breast cancer cells of the basal B subtype. BMC Cancer 2010;10:568.
42. Muller WJ, Sinn E, Pattengale PK, Wallace R, Leder P. Single-step induction ofmammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 1988;54:105-15.
43. Huang F, Reeves K, Han X, Fairchild C, Platero S, Wong TW, et al. Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib: rationale for patient selection 2007;2226-38.
44. Marcotte R, Smith HW, Sanguin-Gendreau V, McDonough RV, Muller WJ. Mammary epithelial-specific disruption of c-Src impairs cell cycle progression and tumorigenesis. Proc Natl Acad Sci U S A 2012; 109:2808-13.
45. Karim SA, Creedon H, Patel H, Carragher NO, Morton JP, Muller WJ, et al. Dasatinib inhibits mammary tumour development in a genetically engineered mouse model. J Pathol 2013;230:430-40.
46. Phung TL, Eyiah-Mensah G, O'Donnell RK, Bieniek R, Shechter S, Walsh K, et al. Endothelial Akt signaling is rate-limiting for rapamycin inhibition of mouse mammary tumor progression. Cancer Res 2007;67:5070-5.
47. Miller TW, Forbes JT, Shah C, Wyatt SK, Manning HC, Olivares MG, et al. Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpres-sing cancer cells. Clin Cancer Res 2009;15:7266-76.
48. Torres-Arzayus MI, Yuan J, DellaGatta JL, Lane H, Kung AL, Brown M. Targeting the AIB1 oncogene through mammalian target of rapamycin inhibition in the mammary gland. Cancer Res 2006;66: 11381-8.
49. Zhang Q, Bindokas V, Shen J, Fan H, Hoffman RM, Xing HR. Time-course imaging of therapeutic functional tumor vascular normalization by antiangiogenic agents. Mol Cancer Ther 2011;10:1173-84.
50. Coluccia AML, Cirulli T, Neri P, Mangieri D, Colanardi MC, Gnoni A, et al. Validation of PDGFRb and c-Src tyrosine kinases as tumor/vessel targets in patients with multiple myeloma: preclinical efficacy of the novel, orally available inhibitor dasatinib. Blood 2008;112: 1346-56.
51. Haubeiss S, Schmid JO, Murdter TE, Sonnenberg M, Friedel G, van der Kuip H, et al. Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer 2010;9:168.