Endocrine resistance in breast cancer: Focus on the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling pathway

Breast Care

Volumn 8, Issue 4, 2013, Pages 248-255

  Peleg Hasson, Shira ^a,b   Rubinek, Tami ^a   Ryvo, Larysa ^a   Wolf, Ido ^a,b  

^a TEL AVIV SOURASKY MEDICAL CENTER   (Israel)

^b TEL AVIV UNIVERSITY   (Israel)

Author keywords

Endocrine resistance; Estrogen receptor; Hormone receptor positive breast cancer; PI3K mTOR pathway

Indexed keywords

ESTROGEN; ESTROGEN RECEPTOR ALPHA; EVEROLIMUS; EXEMESTANE; LETROZOLE; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROGESTERONE RECEPTOR; PROTEIN KINASE B; RAPAMYCIN; TAMOXIFEN; TEMSIROLIMUS; TUBERIN;

ADD ON THERAPY; ADJUVANT CHEMOTHERAPY; BREAST CANCER; BREAST METASTASIS; CANCER RESISTANCE; CLINICAL TRIAL (TOPIC); ENDOCRINE RESISTANCE; ENDOCRINE SYSTEM; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; HORMONE SENSITIVITY; HUMAN; NEGATIVE FEEDBACK; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION;

EID: 84885101526     PISSN: 16613791     EISSN: 16613805     Source Type: Journal    
DOI: 10.1159/000354757     Document Type: Review

References (54)

1. Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.
2. Osborne CK, Schiff R: Mechanisms of endocrine resistance in breast cancer. Annu Rev Med 2011; 62:233-247.
3. Liu P, Cheng H, Roberts TM, Zhao JJ: Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 2009;8:627-644.
4. Stoica GE, Franke TF, Moroni M, Mueller S, Morgan E, Iann MC, Winder AD, Reiter R, Wellstein A, Martin MB, Stoica A: Effect of estradiol on estrogen receptor-alpha gene expression and activity can be modulated by the Erbb2/PI 3-K/ Akt pathway. Oncogene 2003;22:7998-8011.
5. Ascenzi P, Bocedi A, Marino M: Structure-function relationship of estrogen receptor alpha and beta: impact on human health. Mol Aspects Med 2006;27:299-402.
6. Klinge CM: Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res 2001;29:2905-2919.
7. Levin ER, Pietras RJ: Estrogen receptors outside the nucleus in breast cancer. Breast Cancer Res Treat 2008;108:351-361.
8. Early Breast Cancer Trialists' Collaborative Group (EBCTCG): Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687-1717.
9. Johnston SR, Dowsett M: Aromatase inhibitors for breast cancer: lessons from the laboratory. Nat Rev Cancer 2003;3:821-831.
10. Smith IE, Dowsett M: Aromatase inhibitors in breast cancer. N Engl J Med 2003;348:2431-2442.
11. Buzdar AU: Fulvestrant-a novel estrogen receptor antagonist for the treatment of advanced breast cancer. Drugs Today 2008;44:679-692.
12. Musgrove EA, Sutherland RL: Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer 2009;9:631-643.
13. Hers I, Vincent EE, Tavare JM: Akt signalling in health and disease. Cell Signal 2011;23:1515-1527.
14. Miller TW, Rexer BN, Garrett JT, Arteaga CL: Mutations in the phosphatidylinositol 3-kinase pathway: Role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res 2011;13:224.
15. Yang Q, Guan KL: Expanding mTOR signaling. Cell Res 2007;17:666-681.
16. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, Baselga J, Rosen N: mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006;66:1500-1508.
17. 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, Pandolfi PP: Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest 2008;118:3065-3074.
18. Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, Majumder PK, Baselga J, Rosen N: Akt inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 2011; 19:58-71.
19. Burris HA 3rd: Overcoming acquired resistance to anticancer therapy: Focus on the PI3K/Akt/mTOR pathway. Cancer Chemother Pharmacol 2013;71: 829-842.
20. Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM, Lawrence MS, Sivachenko AY, Sougnez C, Zou L, Cortes ML, Fernandez-Lopez JC, Peng S, Ardlie KG, Auclair D, Bautista-Pina V, Duke F, Francis J, Jung J, Maffuz-Aziz A, Onofrio RC, Parkin M, Pho NH, Quintanar-Jurado V, Ramos AH, Rebollar-Vega R, Rodriguez-Cuevas S, Romero-Cordoba SL, Schumacher SE, Stransky N, Thompson KM, Uribe-Figueroa L, Baselga J, Beroukhim R, Polyak K, Sgroi DC, Richardson AL, Jimenez-Sanchez G, Lander ES, Gabriel SB, Garraway LA, Golub TR, Melendez-Zajgla J, Toker A, Getz G, Hidalgo-Miranda A, Meyerson M: Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 2012;486:405-409.
21. Cancer Genome Atlas Network: Comprehensive molecular portraits of human breast tumours. Nature 2012;490:61-70.
22. Kalinsky K, Jacks LM, Heguy A, Patil S, Drobnjak M, Bhanot UK, Hedvat CV, Traina TA, Solit D, Gerald W, Moynahan ME: PIK3CA mutation associates with improved outcome in breast cancer. Clin Cancer Res 2009;15:5049-5059.
23. Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, Nakshatri H: Phosphatidylinositol 3-kinase/Akt-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J Biol Chem 2001;276:9817-9824.
24. Clark AS, West K, Streicher S, Dennis PA: Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther 2002;1:707-717.
25. Jordan NJ, Gee JM, Barrow D, Wakeling AE, Nicholson RI: Increased constitutive activity of PKB/ Akt in tamoxifen resistant breast cancer MCF-7 cells. Breast Cancer Res Treat 2004;87:167-180.
26. deGraffenried LA, Friedrichs WE, Russell DH, Donzis EJ, Middleton AK, Silva JM, Roth RA, Hidalgo M: Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt activity. Clin Cancer Res 2004;10: 8059-8067.
27. 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.
28. Miller TW, Hennessy BT, Gonzalez-Angulo AM, Fox EM, Mills GB, Chen H, Higham C, Garcia-Echeverria C, Shyr Y, Arteaga CL: Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J Clin Invest 2010;120:2406-2413.
29. Perez-Tenorio G, Stal O: Activation of Akt/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br J Cancer 2002;86: 540-545.
30. Kirkegaard T, Witton CJ, McGlynn LM, Tovey SM, Dunne B, Lyon A, Bartlett JM: Akt activation predicts outcome in breast cancer patients treated with tamoxifen. J Pathol 2005;207:139-146.
31. Tokunaga E, Kimura Y, Mashino K, Oki E, Kataoka A, Ohno S, Morita M, Kakeji Y, Baba H, Maehara Y: Activation of PI3K/Akt signaling and hormone resistance in breast cancer. Breast Cancer 2006;13:137-144.
32. Tokunaga E, Kataoka A, Kimura Y, Oki E, Mashino K, Nishida K, Koga T, Morita M, Kakeji Y, Baba H, Ohno S, Maehara Y: The association between Akt activation and resistance to hormone therapy in metastatic breast cancer. Eur J Cancer 2006;42:629-635.
33. Shoman N, Klassen S, McFadden A, Bickis MG, Torlakovic E, Chibbar R: Reduced PTEN expression predicts relapse in patients with breast carcinoma treated by tamoxifen. Mod Pathol 2005; 18:250-259.
34. Vezina C, Kudelski A, Sehgal SN: Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot (Tokyo) 1975; 28:721-726.
35. Benjamin D, Colombi M, Moroni C, Hall MN: Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat Rev Drug Discov 2011;10: 868-880.
36. Meric-Bernstam F, Gonzalez-Angulo AM: Targeting the mTOR signaling network for cancer therapy. J Clin Oncol 2009;27:2278-2287.
37. Fiebig HH, Berger DP, Winterhalter BR, Plowman J: In vitro and in vivo evaluation of US-NCI compounds in human tumor xenografts. Cancer Treat Rev 1990;17:109-117.
38. Shi Y, Frankel A, Radvanyi LG, Penn LZ, Miller RG, Mills GB: Rapamycin enhances apoptosis and increases sensitivity to cisplatin in vitro. Cancer Res 1995;55:1982-1988.
39. Ghayad SE, Bieche I, Vendrell JA, Keime C, Lidereau R, Dumontet C, Cohen PA: mTOR inhibition reverses acquired endocrine therapy resistance of breast cancer cells at the cell proliferation and gene-expression levels. Cancer Sci 2008;99: 1992-2003.
40. Boulay A, Rudloff J, Ye J, Zumstein-Mecker S, O'Reilly T, Evans DB, Chen S, Lane HA: 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.
41. Creighton CJ, Fu X, Hennessy BT, Casa AJ, Zhang Y, Gonzalez-Angulo AM, Lluch A, Gray JW, Brown PH, Hilsenbeck SG, Osborne CK, Mills GB, Lee AV, Schiff R: Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer. Breast Cancer Res 2010;12:R40.
42. Cavazzoni A, Bonelli MA, Fumarola C, La Monica S, Airoud K, Bertoni R, Alfieri RR, Galetti M, Tramonti S, Galvani E, Harris AL, Martin LA, Andreis D, Bottini A, Generali D, Petronini PG: Overcoming acquired resistance to letrozole by targeting the PI3K/Akt/mTOR pathway in breast cancer cell clones. Cancer Lett 2012;323:77-87.
43. Sanchez CG, Ma CX, Crowder RJ, Guintoli T, Phommaly C, Gao F, Lin L, Ellis MJ: Preclinical modeling of combined phosphatidylinositol-3-kinase inhibition with endocrine therapy for estrogen receptor-positive breast cancer. Breast Cancer Res 2011;13:R21.
44. Ellard SL, Clemons M, Gelmon KA, Norris B, Kennecke H, Chia S, Pritchard K, Eisen A, Vandenberg T, Taylor M, Sauerbrei E, Mishaeli M, Huntsman D, Walsh W, Olivo M, McIntosh L, Seymour L: Randomized phase II study comparing two schedules of everolimus in patients with recurrent/ metastatic breast cancer: NCIC Clinical Trials Group IND.163. J Clin Oncol 2009;27:4536-4541.
45. Baselga J, Semiglazov V, van Dam P, Manikhas A, Bellet M, Mayordomo J, Campone M, Kubista E, Greil R, Bianchi G, Steinseifer J, Molloy B, Tokaji E, Gardner H, Phillips P, Stumm M, Lane HA, Dixon JM, Jonat W, Rugo HS: 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.
46. 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 2012;30:2718-2724.
47. Safra TM, MD GJ, Rivo LM, Kaufman B, Evron EM, Ben Baruch NM, Kadouri-Sonenfeld LM, Nisenbaum BM, Yerushalmi RM: RAD001 (everolimus) in combination with letrozole in the treatment of postmenopausal women with estrogen receptor positive metastatic breast cancer after failure of hormonal therapy-a phase II study. Abstr. SABCS 2012.
48. 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, Hortobagyi GN: Everolimus in postmenopausal hormone-receptorpositive advanced breast cancer. N Engl J Med 2012;366:520-529.
49. Noguchi S, Masuda N, Iwata H, Mukai H, Horiguchi J, Puttawibul P, Srimuninnimit V, Tokuda Y, Kuroi K, Iwase H, Inaji H, Ohsumi S, Noh WC, Nakayama T, Ohno S, Rai Y, Park BW, Panneerselvam A, El-Hashimy M, Taran T, Sahmoud T, Ito Y: Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptorpositive breast cancer in BOLERO-2. Breast Cancer 2013;Feb 13 [Epub ahead of print].
50. Chan S, Scheulen ME, Johnston S, Mross K, Cardoso F, Dittrich C, Eiermann W, Hess D, Morant R, Semiglazov V, Borner M, Salzberg M, Ostapenko V, Illiger HJ, Behringer D, Bardy-Bouxin N, Boni J, Kong S, Cincotta M, Moore L: Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol 2005;23:5314-5322.
51. Carpenter JT, Roche H, Campone M, et al: Randomized 3-arm, phase 2 study of temsirolimus (CCI-779) in combination with letrozole in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol 2005;23(suppl 16):abstr 564.
52. Wolff AC, Lazar AA, Bondarenko I, Garin AM, Brincat S, Chow L, Sun Y, Neskovic-Konstantinovic Z, Guimaraes RC, Fumoleau P, Chan A, Hachemi S, Strahs A, Cincotta M, Berkenblit A, Krygowski M, Kang LL, Moore L, Hayes DF: Randomized phase III placebo-controlled 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.
53. Villarreal-Garza C, Cortes J, Andre F, Verma S: mTOR inhibitors in the management of hormone receptor-positive breast cancer: The latest evidence and future directions. Ann Oncol 2012;23:2526-2535.
54. Loi S, Michiels S, Baselga J, Bartlett JM, Singhal SK, Sabine VS, Sims AH, Sahmoud T, Dixon JM, Piccart MJ, Sotiriou C: PIK3CA genotype and a PIK3CA mutation-related gene signature and response to everolimus and letrozole in estrogen receptor positive breast cancer. PLoS One. 2013;8:e53292.