Role of mtor inhibition in preventing resistance and restoring sensitivity to hormone-targeted and her2-targeted therapies in breast cancer

Clinical Advances in Hematology and Oncology

Volumn 11, Issue 4, 2013, Pages 217-224

  Mayer, Ingrid ^a  

^a VANDERBILT INGRAM CANCER CENTER   (United States)

Author keywords

Breast neoplasms; Everolimus; mTOR inhibitors; Ridaforolimus; Temsirolimus

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL) IMIDAZO [4, 5 C] QUINOLIN 2 (1H, 3H) ONE; ANASTROZOLE; CIXUTUMUMAB; DALOTUZUMAB; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EVEROLIMUS; EXEMESTANE; FULVESTRANT; LETROZOLE; MAMMALIAN TARGET OF RAPAMYCIN; NAVELBINE; NERATINIB; PACLITAXEL; PLACEBO; RAPAMYCIN; RIDAFOROLIMUS; TAMOXIFEN; TEMSIROLIMUS; TRASTUZUMAB; UNCLASSIFIED DRUG; XL 147; XL 765;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CELL GROWTH; CELL PROLIFERATION; CELL STRUCTURE; DISEASE ASSOCIATION; DRUG EFFECT; GENE EXPRESSION; GENE MUTATION; GROWTH REGULATION; HORMONAL THERAPY; HUMAN; LYMPH NODE METASTASIS; MICROARRAY ANALYSIS; MOLECULARLY TARGETED THERAPY; MULTICENTER STUDY (TOPIC); NEUTROPENIA; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIGNAL TRANSDUCTION; STOMATITIS;

ANTINEOPLASTIC AGENTS, HORMONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BREAST NEOPLASMS; CLINICAL TRIALS AS TOPIC; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTOR, ERBB-2; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 84878038749     PISSN: 15430790     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (63)

1. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747-752.
2. Hurvitz SA, Pietras RJ. Rational management of endocrine resistance in breast cancer: a comprehensive review of estrogen receptor biology, treatment options, and future directions. Cancer. 2008;113:2385-2397.
3. Arteaga CL, Sliwkowski MX, Osborne CK, Perez EA, Puglisi F, Gianni L. Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol. 2012;9:16-32.
4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer Screening and Diagnosis, V1.2011. Fort Washington, PA: NCCN; 2011.
5. Bender LM, Nahta R. Her2 cross talk and therapeutic resistance in breast cancer. Front Biosci. 2008;13:3906-3912.
6. Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol. 2006;3:269-280.
7. Pegram M. Can we circumvent resistance to ErbB2-targeted agents by targeting novel pathways? Clin Breast Cancer. 2008;8(suppl 3):S121-S130.
8. Yuan R, Kay A, Berg WJ, Lebwohl D. Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy. J Hematol Oncol. 2009;2:45-54.
9. McAuliffe PF, Meric-Bernstam F, Mills GB, Gonzalez-Angulo AM. Deciphering the role of PI3K/Akt/mTOR pathway in breast cancer biology and pathogenesis. Clin Breast Cancer. 2010;10(suppl 3):S59-S65.
10. Yang Q, Inoki K, Kim E, Guan KL. TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity. Proc Natl Acad Sci U S A. 2006;103:6811-6816.
11. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489-501.
12. Marsh DJ, Dahia PL, Zheng Z, et al. Germline mutations in PTEN are present in Bannayan-Zonana syndrome. Nat Genet. 1997;16:333-334.
13. Lali FV, Hunt AE, Turner SJ, Foxwell BM. The pyridinyl imidazole inhibitor SB203580 blocks phosphoinositide-dependent protein kinase activity, protein kinase B phosphorylation, and retinoblastoma hyperphosphorylation in interleukin-2-stimulated T cells independently of p38 mitogen-activated protein kinase. J Biol Chem. 2000;275:7395-7402.
14. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;7:606-619.
15. Saal LH, Holm K, Maurer M, 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;65:2554-2559.
16. Bachman KE, Argani P, Samuels Y, et al. The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther. 2004;3:772-775.
17. Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, et al. An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 2008;68:6084-6091.
18. Barbareschi M, Buttitta F, Felicioni L, et al. Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas. Clin Cancer Res. 2007;13:6064-6069.
19. Serra V, Markman B, Scaltriti 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;68:8022-8030.
20. Berns K, Horlings HM, Hennessy BT, 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.
21. Nagata Y, Lan KH, Zhou X, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004;6:117-127.
22. Yu K, Toral-Barza L, Discafani C, et al. mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Endocr Relat Cancer. 2001;8:249-258.
23. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 2007;12:9-22.
24. TORISEL Kit (temsirolimus) injection, for intravenous infusion only [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc; September 2010.
25. AFINITOR (everolimus) tablets for oral administration package insert. East Hanover, NJ; Novartis Pharmaceuticals Corporation; July 2012.
26. Miller TW, Hennessy BT, Gonzalez-Angulo AM, et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J Clin Invest. 2010;120:2406-2413.
27. Sun M, Paciga JE, Feldman RI, et al. Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K. Cancer Res. 2001;61:5985-5991.
28. deGraffenried LA, Friedrichs WE, Russell DH, et al. Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt activity. Clin Cancer Res. 2004;10:8059-8067.
29. Boulay A, Rudloff J, Ye J, et al. Dual inhibition of mTOR and estrogen receptor signaling in vitro induces cell death in models of breast cancer. Clin Cancer Res. 2005;11:5319-5328.
30. Beeram M, Tan QT, Tekmal RR, Russell D, Middleton A, deGraffenried LA. Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling. Ann Oncol. 2007;18:1323-1328.
31. Ghayad SE, Bieche I, Vendrell JA, et al. mTOR inhibition reverses acquired endocrine therapy resistance of breast cancer cells at the cell proliferation and geneexpression levels. Cancer Sci. 2008;99:1992-2003.
32. Farmer I, Evans DB, Lane HA, Lykesffelt EV, Dowsett M, Martin L.Preclinical studies of the combination of RADO01 with tamoxifen or letrozole in breast cancer. Eur J Cancer. 2006;4(suppl 2):142. Abstract 324.
33. Treeck O, Wackwitz B, Haus U, Ortmann O. Effects of a combined treatment with mTOR inhibitor RAD001 and tamoxifen in vitro on growth and apoptosis of human cancer cells. Gynecol Oncol. 2006;102:292-299.
34. Baselga J, Roche H, Fumoleau P. Treatment of postmenopausal women with locally advanced or metastatic breast cancer with letrozole alone or in combination with temsirolimus: a randomized, 3-arm, phase 2 study. Presented at: 28th Annual San Antonio Breast Cancer Symposium; December 8-11, 2005; San Antonio, TX.
35. Wolff AC, Lazar AA, Bondarenko I, et al. Randomized phase III placebocontrolled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol. 2013;31:195-202.
36. Awada A, Cardoso F, Fontaine C, et al. The oral mTOR inhibitor RAD001 (everolimus) in combination with letrozole in patients with advanced breast cancer: results of a phase I study with pharmacokinetics. Eur J Cancer. 2008;44:84-91.
37. Baselga J, Semiglazov V, van Dam P, et al. Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer. J Clin Oncol. 2009;27:2630-2637.
38. Bachelot T, Bourgier C, Cropet C, et al. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, HER2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol. 2012;30:2718-2724.
39. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone receptor-positive advanced breast cancer. N Engl J Med. 2012;366:520-529.
40. Baselga J, Campone M, Sahmoud T, et al. Everolimus in combination with exemestane for postmenopausal women with advanced breast cancer who are refractory to letrozole or anastrozole: results of the BOLERO-2 phase III trial. Presented at: 2011 European Multidisciplinary Cancer Congress (ECCO/ESMO); September 23-27, 2011; Stockholm, Sweden.
41. Hortobagyi GN, Piccart M, Rugo H, et al. Everolimus for postmenopausal women with advanced breast cancer: updated results of the BOLERO 2 phase III trial. Presented at: 34th Annual San Antonio Breast Cancer Symposium; December 6-10, 2011; San Antonio, TX.
42. Rugo HS, Pritchard KI, Gnant M, et al. Everolimus (EVE) for postmenopausal women with advanced breast cancer (ABC) refractory to letrozole or anastrozole: long-term efficacy and safety results of the BOLERO-2 trial. Presented at: 8th European Breast Cancer Conference; March 21-24, 2012; Vienna, Austria.
43. Piccart M, Noguchi S, Pritchard KI, et al. Everolimus for postmenopausal women with advanced breast cancer: updated results of the BOLERO-2 phase III trial. Poster presented at: 48th Annual Meeting of the American Society for Clinical Oncology; June 1-5, 2012; Chicago, IL.
44. Chan CT, Metz MZ, Kane SE. Differential sensitivities of trastuzumab (Herceptin)-resistant human breast cancer cells to phosphoinositide-3 kinase (PI--3K) and epidermal growth factor receptor (EGFR) kinase inhibitors. Breast Cancer Res Treat. 2005;91:187-201.
45. Miller TW, Forbes JT, Shah C, et al. Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells. Clin Cancer Res. 2009;15:7266-7276.
46. Lu CH, Wyszomierski SL, Tseng LM, et al. Preclinical testing of clinically applicable strategies for overcoming trastuzumab resistance caused by PTEN deficiency. Clin Cancer Res. 2007;13:5883-5888.
47. Andre F, Campone M, O'Regan R, 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;28:5110-5115.
48. Jerusalem G, Fasolo A, Dieras V, et al. Phase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer. Breast Cancer Res Treat. 2011;125:447-455.
49. www.ClinicalTrials.gov. Daily everolimus in combination with trastuzumab and vinorelbine in HER2/neu positive women with locally advanced or metastatic breast cancer (BOLERO-3). http://clinicaltrials.gov/ct2/show/NCT01007942?ter m=NCT01007942&rank=1. Identifier: NCT01007942.
50. O'Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006;66:1500-1508.
51. www.ClinicalTrials.gov. Study of XL147 (SAR245408) or XL765 (SAR245409) in combination with letrozole in subjects with breast cancer. Identifier: NCT01082068.
52. www.ClinicalTrials.gov. PhIb BKM120 or BEZ235+endocrine treatment in post-menopausal patients with hormone receptor + metastatic breast cancer. Identifier: NCT01248494.
53. www.ClinicalTrials.gov. Study of XL147 (SAR245408) in combination with trastuzumab or paclitaxel and trastuzumab in subjects with metastatic breast cancer who have progressed on a previous trastuzumab-based regimen. Identifier: NCT01042925.
54. www.ClinicalTrials.gov. Dose escalation followed by study of RAD001 in combination with trastuzumab in HER2-positive metastatic breast cancer. http://www. clinicaltrials.gov/ct2/show/NCT00458237?term=00458237&rank=1. Identifier: NCT00458237.
55. www.ClinicalTrials.gov. Trastuzumab and RAD001 in patients with human epidermal growth receptor 2 (HER-2) overexpressing breast cancer. http://www. clinicaltrials.gov/ct2/show/NCT00317720?term=00317720&rank=1. Identifier: NCT00317720.
56. www.ClinicalTrials.gov. Efficacy and safety of everolimus in combination therapy, in patients with HER2-overexpressing metastatic breast cancer. http://www.clinicaltrials.gov/ct2/show/NCT00426556?term=00426556&rank=1. Identifier: NCT00426556.
57. www.ClinicalTrials.gov. Study of combined fulvestrant and RAD001 in advanced/metastatic breast cancer after aromatase inhibitor failure (BRE-43). http://www.clinicaltrials.gov/ct2/show/NCT00570921?term=00570921&r ank=1. Identifier: NCT00570921.
58. www.ClinicalTrials.gov. Randomized phase II trial of trastuzumab or everolimus in hormone-refractory metastatic breast cancer. http://www.clinicaltrials.gov/ ct2/show/NCT00912340?term=00912340&rank=1. Identifier: NCT00912340.
59. www.ClinicalTrials.gov. Everolimus in combination with exemestane in the treatment of postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer who are refractory to letrozole or anastrozole (BOLERO2). http://www.clinicaltrials.gov/ct2/show/NCT00863655?term=0086 3655&rank=1. Identifier: NCT00863655.
60. www.ClinicalTrials.gov. A study of ridaforolimus (MK-8669) in combination with dalotuzumab (MK-0646) compared to standard of care treatment in estrogen receptor positive breast cancer patients (MK-8669-041 AM3). http://www. clinicaltrials.gov/ct2/show/NCT01234857?term=01234857&rank=1. Identifier: NCT01234857.
61. www.ClinicalTrials.gov. A phase II study of rapamycin and trastuzumab for patients with HER-2 receptor positive metastatic breast cancer. http://www.clinicaltrials.gov/ct2/show/NCT00411788?term=00411788&rank=1. Identifier: NCT00411788.
62. www.ClinicalTrials.gov. Temsirolimus plus neratinib for patients with metastatic HER2-amplified or triple negative breast cancer. http://www.clinicaltrials.gov/ct2/show/NCT01111825?term=01111825&rank=1. Identifier: NCT01111825.
63. www.ClinicalTrials.gov. Cixutumumab and temsirolimus in treating patients with locally recurrent or metastatic breast cancer. http://www.clinicaltrials.gov/ct2/show/NCT00699491?term=00699491&rank=1. Identifier: NCT00699491.