Targeting PI3K/mTOR overcomes resistance to HER2-targeted therapy independent of feedback activation of AKT

Clinical Cancer Research

Volumn 20, Issue 13, 2014, Pages 3507-3520

  O'Brien, Neil A ^a   McDonald, Karen ^a   Tong, Luo ^a   Von Euw, Erika ^a   Kalous, Ondrej ^a   Conklin, Dylan ^a   Hurvitz, Sara A ^a   Di Tomaso, Emmanuelle ^b   Schnell, Christian ^b   Linnartz, Ronald ^b   Finn, Richard S ^a   Hirawat, Samit ^b   Slamon, Dennis J ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

BUPARLISIB; DACTOLISIB; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; EVEROLIMUS; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; NVP BYL 719; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN KINASE B; TRASTUZUMAB; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY; PROTEIN KINASE INHIBITOR; TARGET OF RAPAMYCIN KINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER INHIBITION; CONTROLLED STUDY; DRUG POTENTIATION; DRUG TARGETING; ENZYME INHIBITION; FEEDBACK SYSTEM; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOLECULARLY TARGETED THERAPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; TUMOR REGRESSION; ANIMAL; ANTAGONISTS AND INHIBITORS; BREAST NEOPLASMS; CELL CYCLE CHECKPOINT; CELL PROLIFERATION; DISEASE MODEL; DRUG EFFECTS; DRUG RESISTANCE; DRUG SCREENING; FEMALE; GENETICS; METABOLISM; MORTALITY; MUTATION; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; APOPTOSIS; BREAST NEOPLASMS; CELL CYCLE CHECKPOINTS; CELL LINE, TUMOR; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; MICE; MOLECULAR TARGETED THERAPY; MUTATION; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTOR, ERBB-2; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84903840245     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-13-2769     Document Type: Article

References (50)

1. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987;235: 177-82.
2. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989;244: 707-12.
3. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006;355: 2733-43.
4. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005;353: 1673-84.
5. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001;344: 783-92.
6. Montemurro F, Valabrega G, Aglietta M. Trastuzumab-based combination therapy for breast cancer. Expert Opin Pharmacother 2004;5: 81-96.
7. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002;20: 719-26.
8. Garrett TP, McKern NM, Lou M, Elleman TC, Adams TE, Lovrecz GO, et al. The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Mol Cell 2003;11: 495-505.
9. Wallasch C, Weiss FU, Niederfellner G, Jallal B, Issing W, Ullrich A. Heregulin-dependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3. EMBO J 1995;14: 4267-75.
10. Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell 2009;15: 429-40.
11. Browne BC, Crown J, Venkatesan N, Duffy MJ, Clynes M, Slamon D, et al. Inhibition of IGF1R activity enhances response to trastuzumab in HER-2-positive breast cancer cells. Ann Oncol 2011;22: 68-73.
12. Jerome L, Alami N, Belanger S, Page V, Yu Q, Paterson J, et al. Recombinant human insulin-like growth factor binding protein 3 inhibits growth of human epidermal growth factor receptor-2-overexpressing breast tumors and potentiates herceptin activity in vivo. Cancer Res 2006;66: 7245-52.
13. Sergina NV, Rausch M, Wang D, Blair J, Hann B, Shokat KM, et al. Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature 2007;445: 437-41.
14. Zhang S, Huang WC, Li P, Guo H, Poh SB, Brady SW, et al. Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways. Nat Med 2011;17: 461-9.
15. Price-Schiavi SA, Jepson S, Li P, Arango M, Rudland PS, Yee L, et al. Rat Muc4 (sialomucin complex) reduces binding of anti-ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance. Int J Cancer 2002;99: 783-91.
16. Scaltriti M, Rojo F, Ocana A, Anido J, Guzman M, Cortes J, et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst 2007;99: 628-38.
17. Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 2007;12: 395-402.
18. Massarweh S, Schiff R. Unraveling the mechanisms of endocrine resistance in breast cancer: new therapeutic opportunities. Clin Cancer Res 2007;13: 1950-4.
19. Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 2004; 6: 117-27.
20. O'Brien NA, Browne BC, Chow L, Wang Y, Ginther C, Arboleda J, et al. Activated phosphoinositide 3-kinase/AKT signaling confers resistance to trastuzumab but not lapatinib. Mol Cancer Ther 2010;9: 1489-502.
21. Isakoff SJ, Engelman JA, Irie HY, Luo J, Brachmann SM, Pearline RV, et al. Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells. Cancer Res 2005;65: 10992-1000.
22. Li DM, Sun H. PTEN/MMAC1/TEP1 suppresses the tumorigenicity and induces G1 cell-cycle arrest in human glioblastoma cells. Proc Natl Acad Sci U S A 1998;95: 15406-11.
23. Cancer Genome Atlas N. Comprehensive molecular portraits of human breast tumours. Nature 2012;490: 61-70.
24. Hay N. The Akt-mTOR tango and its relevance to cancer. Cancer Cell 2005;8: 1799-83.
25. 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.
26. Furet P, Guagnano V, Fairhurst RA, Imbach-Weese P, Bruce I, Knapp M, et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett 2013;23: 3741-8.
27. Maira SM, Pecchi S, Huang A, Burger M, Knapp M, Sterker D, et al. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol Cancer Ther 2012;11: 317-28.
28. Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C, Fritsch C, et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther 2008;7: 1851-63.
29. Breuleux M, Klopfenstein M, Stephan C, Doughty CA, Barys L, Maira SM, et al. Increased AKT S473 phosphorylation after mTORC1 inhibition is rictor dependent and does not predict tumor cell response to PI3K/mTOR inhibition. Mol Cancer Ther 2009;8: 742-53.
30. Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, 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 2009;11: R77.
31. Ginther C, Issel-Tarver L, King MC. Identifying individuals by sequencing mitochondrial DNA from teeth. Nat Genet 1992;2: 135-8.
32. Uphoff CC, Drexler HG. Detection of mycoplasma in leukemia-lymphoma cell lines using polymerase chain reaction. Leukemia 2002; 16: 289-93.
33. Konecny GE, Pegram MD, Venkatesan N, Finn R, Yang G, Rahmeh M, et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res 2006;66: 1630-9.
34. van Oostrum J, Calonder C, Rechsteiner D, Ehrat M, Mestan J, Fabbro D, et al. Tracing pathway activities with kinase inhibitors and reverse phase protein arrays. Proteomics Clin Appl 2009;3: 412-22.
35. Press MF, Slamon DJ, Flom KJ, Park J, Zhou JY, Bernstein L. Evaluation of HER-2/neu gene amplification and overexpression: comparison of frequently used assay methods in a molecularly characterized cohort of breast cancer specimens. J Clin Oncol 2002;20: 3095-105.
36. Serra V, Markman B, Scaltriti M, Eichhorn PJ, Valero V, Guzman M, et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res 2008;68: 8022-30.
37. Chakrabarty A, Sanchez V, Kuba MG, Rinehart C, Arteaga CL. Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors. Proc Natl Acad Sci U S A 2012; 109: 2718-23.
38. 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.
39. Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res 2010;70: 440-6.
40. Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, et al. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 2005;65: 2554-9.
41. Atkins MB, Yasothan U, Kirkpatrick P. Everolimus. Nat Rev Drug Discov 2009;8: 535-6.
42. Baselga J, Campone M, Piccart M, Burris HA III, Rugo HS, Sahmoud T, et al. Everolimus in postmenopausal hormone receptor-positive advanced breast cancer. N Engl J Med 2012;366: 520-9.
43. Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, et al. Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 2005;65: 7052-8.
44. Beuvink I, Boulay A, Fumagalli S, Zilbermann F, Ruetz S, O'Reilly T, et al. The mTOR inhibitor RAD001 sensitizes tumor cells to DNAdamaged induced apoptosis through inhibition of p21 translation. Cell 2005;120: 747-59.
45. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307: 1098-101.
46. Lane HA, Wood JM, McSheehy PM, Allegrini PR, Boulay A, Brueggen J, et al. mTOR inhibitor RAD001 (everolimus) has antiangiogenic/vascular properties distinct from a VEGFR tyrosine kinase inhibitor. Clin Cancer Res 2009;15: 1612-22.
47. Manegold PC, Paringer C, Kulka U, Krimmel K, Eichhorn ME, Wilkowski R, et al. Antiangiogenic therapy with mammalian target of rapamycin inhibitor RAD001 (Everolimus) increases radiosensitivity in solid cancer. Clin Cancer Res 2008;14: 892-900.
48. Andre F, Campone M, O'Regan R, Manlius C, Massacesi C, Sahmoud T, et al. Phase I study of everolimus plus weekly paclitaxel and trastuzumab in patients with metastatic breast cancer pretreated with trastuzumab. J Clin Oncol 2010;28: 5110-5.
49. Morrow PK, Wulf GM, Ensor J, Booser DJ, Moore JA, Flores PR, et al. Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. J Clin Oncol 2011;29: 3126-32.
50. O'Regan R, Ozguroglu M, Andre F, Toi M, Jerusalem GHM, Wilks S, et al. Phase III randomized, double-blind, placebo-controlled multicenter trial of daily everolimus plus weekly trastuzumab and vinorelbine in trastuzumab- resistant, advanced breast cancer (BOLERO-3). J Clin Oncol 31, 2013 (suppl; abstr 505).