The mammalian target of rapamycin inhibitors in breast cancer: Current evidence and future directions

Anticancer Research

Volumn 33, Issue 1, 2013, Pages 21-28

  Malaguti, Paola ^a   Vari, Sabrina ^a   Cognetti, Francesco ^a   Fabi, Alessandra ^a  

^a REGINA ELENA NATIONAL CANCER INSTITUTE   (Italy)

Author keywords

AKT; Breast cancer; Endocrine resistance; Everolimus; MTOR inhibitor; PI3K; Review; Temsirolimus

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; ANASTROZOLE; ANTIESTROGEN; EVEROLIMUS; EXEMESTANE; LETROZOLE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; NAVELBINE; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; TAMOXIFEN; TEMSIROLIMUS; TRASTUZUMAB; XL 147; XL 765;

ARTICLE; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CANCER HORMONE THERAPY; CANCER RESISTANCE; CELL SURVIVAL; DRUG EFFICACY; DRUG SAFETY; ESTROGEN RECEPTOR POSITIVE BREAST CANCER; HUMAN; INTRACELLULAR SIGNALING; PRIORITY JOURNAL; RECEPTOR UPREGULATION;

BREAST NEOPLASMS; CLINICAL TRIALS AS TOPIC; DRUG RESISTANCE, NEOPLASM; ESTROGENS; FEMALE; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS, HORMONE-DEPENDENT; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTOR, ERBB-2; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84873021780     PISSN: 02507005     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (46)

1. Meric-Bernstam F and Gonzalez-Angulo AM: Targeting the mTOR signaling network for cancer therapy. J Clin Oncol 27: 2278-2287, 2009.
2. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, Baselga J and Rosen N: mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates AKT. Cancer Res 66: 1500-1508, 2006.
3. Margariti N, Fox SB, Bottini A and Generali D: Overcoming breast cancer drug resistance with mTOR inhibitors. Could it be a myth or a real possibility in the short-term future? Breast Cancer Res Treat 128(3): 599-606, 2011.
4. Shaw RJ and Cantley LC: RAS, PI(3)K and mTOR signalling controls tumour cell growth. Nature 441(7092): 424-430, 2006.
5. Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu JS, Malmstrom PO, Mansukhani M, Enoksson J, Hibshoosh H, Borg A and Parsons R: PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 65(7): 2554-2559, 2005.
6. Schiff R, Massarweh SA, Shou J, Bharwani L, Mohsin SK and Osborne CK: Cross-talk between estrogen receptor and growth factor pathways as a molecular target for overcoming endocrine resistance. Clin Cancer Res 10 (1 Pt 2): 331S-336S, 2004.
7. Osborne CK and Schiff R: Mechanisms of endocrine resistance in breast cancer. Annu Rev Med 62: 233-247, 2011.
8. Arpino G, Wiechmann L, Osborne CK and Schiff R: Crosstalk between the estrogen receptor and the HER tyrosine kinase receptor family: Molecular mechanism and clinical implications for endocrine therapy resistance. Endocr Rev 29(2): 217-233, 2008.
9. Beeram M, Tan QT, Tekmal RR, Russell D, Middleton A and DeGraffenried LA: AKT-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling. Ann Oncol 18(8): 1323-1328, 2007.
10. Boulay A, Rudloff J, Ye J, Zumstein-Mecker S, O'Reilly T, Evans DB, Chen S and Lane HA: Dual inhibition of mTOR and estrogen receptor signaling "in vitro" induces cell death in models of breast cancer. Clin Cancer Res 11(14): 5319-5328, 2005.
11. Yarden Y: The EGFR family and its ligands in human cancer. Signalling mechanisms and therapeutic opportunities. Eur J Cancer 37(Suppl 4): S3-8, 2001.
12. Slamon DJ, Clark GM, Wong SG et al: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235: 177-182, 1987.
13. Drebin JA, Link VC, Stern DF, Weinberg RA and Greene MI: Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell 41: 697-706, 1985.
14. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ and Press M: Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20(3): 719-726, 2002.
15. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M,Baselga J and Norton L: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11): 783-792, 2001.
16. Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G and Slamon DJ: Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17(9): 2639-2648, 1999.
17. Seidman AD, Fornier MN, Esteva FJ, Tan L, Kaptain S, Bach A, Panageas KS, Arroyo C, Valero V, Currie V, Gilewski T, Theodoulou M, Moynahan ME,Moasser M, Sklarin N, Dickler M, D'Andrea G, Cristofanilli M, Rivera E, Hortobagyi GN, Norton L and Hudis CA: Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol 19(10): 2587-2595, 2001.
18. Pohlmann PR, Mayer IA and Mernaugh R: Resistance to trastuzumab in breast cancer. Clin Cancer Res 15(24): 7479-7491, 2009.
19. Pegram M: Can we circumvent resistance to ERBB2-targeted agents by targeting novel pathways? Clin Breast Cancer 8(Suppl 3): S121-130, 2008.
20. Hennessy BT, Smith DL, Ram PT, Lu Y and Mills GB: Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 4(12): 988-1004, 2005.
21. Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA, Klos KS, Li P, Monia BP, Nguyen NT, Hortobagyi GN, Hung MC and Yu D: PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 6(2): 117-127, 2004.
22. Depowski PL, Rosenthal SI and Ross JS: Loss of expression of the PTEN gene protein product is associated with poor outcome in breast cancer. Mod Pathol 14(7): 672-676, 2001.
23. Schmelzle T and Hall MN: TOR, a central controller of cell growth. Cell 103(2): 253-262, 2000.
24. Vivanco I and Sawyers CL: The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2(7): 489-501, 2002.
25. Nahta R, Yuan LX, Zhang B, Kobayashi R and Esteva FJ: Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res 65(23): 11118-11128, 2005.
26. Carracedo A, Ma L, Teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, Egia A, Sasaki AT, Thomas G, Kozma SC, Papa A, Nardella C, Cantley LC, Baselga J and Pandolfi PP: Inhibition of mTORC1 leads to MAPK pathway activation through a PI3Kdependent feedback loop in human cancer. J Clin Invest 118(9): 3065-3074, 2008.
27. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL and Sabatini DM: Prolonged rapamycin treatment inhibits mTORC2 assembly and AKT/PKB. Mol Cell 22(2): 159-168, 2006.
28. Shaw RJ and Cantley LC. Ras: PI(3)K and mTOR signaling controls tumour cell growth. Nature 441: 424-430; 2006.
29. Sabatini DM: mTOR and cancer: insights into a complex relationship. Nat Rev Cancer 6: 729-734; 2006.
30. Gan X, Wang J, Su B and Wu D: Evidence for direct activation of mTORC2 kinase activity by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 286(13): 10998-11002, 2011.
31. Serra V, Markman B, Scaltriti M, Eichhorn PJ, Valero V, Guzman M, Botero ML, Llonch E, Atzori F, Di Cosimo S, Maira M, Garcia-Echeverria C, Parra JL, Arribas J and Baselga J: NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res 68(19): 8022-8030, 2008.
32. Markman B, Atzori F, Perez-Garcia J, Tabernero J and Baselga J: Status of PI3K inhibition and biomarker development in cancer therapeutics Ann Oncol 21(4): 683-691; 2010.
33. Mohd Sharial MS, Crown J and Hennessy BT: Overcoming resistance and restoring sensitivity to HER2-targeted therapies in breast cancer. Ann Oncol 2012. Abstract.
34. Awada A, Cardoso F, Fontaine C, Dirix L, De Greve J, Sotiriou C, Steinseifer J, Wouters C, Tanaka C, Zoellner U, Tang P and Piccart M: 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 44(1): 84-91, 2008.
35. Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaeth D, Legouffe E, Allouache D, El Kouri C, Pujade-Lauraine E: Randomized Phase II Trial of Everolimus in Combination With Tamoxifen in Patients With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer With Prior Exposure to Aromatase Inhibitors: A GINECO Study. J Clin Oncol 30(22): 2718-2724, 2012.
36. Baselga J, Roche H and Fumoleau P: Treatment of posmenopausal women with locally advanced or metastatic breast cancer with letrozole alone or in combination with temsirolimus: A randomized, 3-arm, phase 2 study. Breast Cancer Res Treat 94(Suppl 1): S62, 2005. Special issue 28th Annual SAN ANTONIO BREAST CANCER SYMPOSIUM.
37. Chow L, Sun Y and Jassem J: Phase 3 study of temsirolimus with letrozole or letrozole alone in postmenopausal women with locally advanced or metastatic brest cancer. Breast Cancer Res Treat 100: 6091, 2006.
38. Baselga J, Semiglazov V and van Dam P: 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 27: 2630-2637, 2009.
39. Roxanne Nelson: FDA Approves Everolimus for Advanced Breast Cancer. Medscape Medical News Jul 20, 2012.
40. Baselga J, Campone M and Sahmound T: 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. Proc 2011 European Multidisciplinary Cancer Congress (ECCO 16, ESMO 36 and ESTRO 30), Stockholm, Sweden: 2011 Future Oncol 2012.
41. Hortobagyi GC, Piccart M and Rugo H: Everolimus for postmenopausal women with advanced breast cancer: Update result of the BOLERO-2 phase III trial Proc 2011 San Antonio Breast Cancer Symposium, Edition San Antonio, US: 2011.
42. Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D and Hortobagyi GN: Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366(6): 520-529, 2012.
43. Andre F, Campone M, O'Regan R, Manlius C, Massacesi C, Sahmoud T, Mukhopadhyay P, Soria JC, Naughton M and Hurvitz SA: Phase I study of everolimus plus weekly paclitaxel and trastuzumab in patients with metastatic breast cancer pretreated with trastuzumab. J Clin Oncol 28(34): 5110-5115, 2010.
44. ClinicalTrials.gov: NCT00426556. Efficacy and Safety of Everolimus in Combination Therapy in Patients With HER2-overexpressing Metastatic Breast Cancer.
45. ClinicalTrials.gov: NCT00876395. Everolimus in Combination With Trastuzumab and Paclitaxel in the Treatment of HER2 Positive Locally Advanced or Metastatic Breast Cancer (BOLERO-1).
46. ClinicalTrials.gov: NCT01007942. Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer (BOLERO-3).