Optimal targeting of HER2-PI3K signaling in breast cancer: Mechanistic insights and clinical implications

Cancer Research

Volumn 73, Issue 13, 2013, Pages 3817-3820

  Rexer, Brent N ^a   Arteaga, Carlos L ^a  

^a VANDERBILT INGRAM CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE DEHYDROGENASE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; EVEROLIMUS; INTERLEUKIN 8; LAPATINIB; PERTUZUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; SURVIVIN; TAXANE DERIVATIVE; TRANSCRIPTION FACTOR FOXO; TRASTUZUMAB; XL 147;

APOPTOSIS; BREAST CANCER; BREAST METASTASIS; CANCER ADJUVANT THERAPY; CANCER INHIBITION; CANCER PROGNOSIS; CANCER RESISTANCE; CANCER STEM CELL; DIMERIZATION; GENE MUTATION; HER2 GENE; HUMAN; MICROMETASTASIS; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CLINICAL TRIALS AS TOPIC; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; MOLECULAR TARGETED THERAPY; PHOSPHATIDYLINOSITOL 3-KINASES; RECEPTOR, ERBB-2; SIGNAL TRANSDUCTION;

EID: 84880065874     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-13-0687     Document Type: Review

References (34)

1. Arnould L, Gelly M, Penault-Llorca F, Benoit L, Bonnetain F, Migeon C, et al. Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? Br J Cancer 2006;94: 259-67.
2. Clynes RA, Towers TL, Presta LG, Ravetch JV. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med 2000;6: 443-6.
3. Cuello M, Ettenberg SA, Clark AS, Keane MM, Posner RH, Nau MM, et al. Down-regulation of the erbB-2 receptor by trastuzumab (herceptin) enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast and ovarian cancer cell lines that overexpress erbB-2. Cancer Res 2001;61: 4892-900.
4. 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.
5. Rexer BN, Arteaga CL. Intrinsic and acquired resistance to HER2- targeted therapies in HER2 gene-amplified breast cancer: mechanisms and clinical implications. Crit Rev Oncog 2012;17: 1-16.
6. Yakes FM, Chinratanalab W, Ritter CA, King W, Seelig S, Arteaga CL. Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt Is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Res 2002;62: 4132-41.
7. Eichhorn PJA, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W, et al. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by themTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res 2008;68: 9221-30.
8. 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.
9. 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.
10. 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.
11. Chakrabarty A, Bhola NE, Sutton C, Ghosh R, Kuba MG, Dave B, et al. Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-Survivin axis and are sensitive to PI3K inhibitors. Cancer Res 2013;73: 1190-200.
12. Ritter CA, Perez-Torres M, Rinehart C, Guix M, Dugger T, Engelman JA, et al.Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin Cancer Res 2007;13: 4909-19.
13. Burke JE, Perisic O, Masson GR, Vadas O, Williams RL. Oncogenic mutations mimic and enhance dynamic events in the natural activation of phosphoinositide 3-kinase p110alpha (PIK3CA). Proc Natl Acad Sci U S A 2012;109: 15259-64.
14. Zhao L, Vogt PK. Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms. Proc Natl Acad Sci U S A 2008;105: 2652-7.
15. 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.
16. Chandarlapaty S, Sakr RA, Giri D, Patil S, Heguy A, Morrow M, et al. Frequent mutational activation of the PI3K-AKT pathway in trastuzumab-resistant breast cancer. Clin Cancer Res 2012;18: 6784-91.
17. Esteva FJ, Guo H, Zhang S, Santa-Maria C, Stone S, Lanchbury JS, et al. PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer. Am J Pathol 2010;177: 1647-56.
18. Razis E, Bobos M, Kotoula V, Eleftheraki AG, Kalofonos HP, Pavlakis K, et al. Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer. Breast Cancer Res Treat 2011;128: 447-56.
19. Wang L, Zhang Q, Zhang J, Sun S, Guo H, Jia Z, et al. PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib. BMC Cancer 2011;11: 248.
20. Mohsin SK, Weiss HL, Gutierrez MC, Chamness GC, Schiff R, Digiovanna MP, et al. Neoadjuvant trastuzumab induces apoptosis in primary breast cancers. J Clin Oncol 2005;23: 2460-8.
21. Liu S, Wicha MS. Targeting breast cancer stem cells. J Clin Oncol 2010;28: 4006-12.
22. Korkaya H, Paulson A, Iovino F, Wicha MS. HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 2008;27: 6120-30.
23. Magnifico A, Albano L, Campaner S, Delia D, Castiglioni F, Gasparini P, et al. Tumor-initiating cells of HER2-positive carcinoma cell lines express the highest oncoprotein levels and are sensitive to trastuzumab. Clin Cancer Res 2009;15: 2010-21.
24. 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.
25. Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, et al. AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 2011;19: 58-71.
26. Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012;366: 109-19.
27. Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2- positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol 2012;30: 2585-92.
28. von Minckwitz G, Schwedler K, Schmidt M, Barinoff J, Mundhenke C, Cufer T, et al. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer 2011;47: 2273-81.
29. Cortes J, Fumoleau P, Bianchi GV, Petrella TM, Gelmon K, Pivot X, et al. Pertuzumab monotherapy after trastuzumab-based treatment and subsequent reintroduction of trastuzumab: activity and tolerability in patients with advanced human epidermal growth factor receptor 2- positive breast cancer. J Clin Oncol 2012;30: 1594-600.
30. Utermark T, Rao T, Cheng H, Wang Q, Lee SH, Wang ZC, et al. The p110alpha and p110beta isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis. Genes Dev 2012;26: 1573-86.
31. Ryan BM, Konecny GE, Kahlert S, Wang HJ, Untch M, Meng G, et al. Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1. Ann Oncol 2006;17: 597-604.
32. Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006;24: 3726-34.
33. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 2012;379: 633-40.
34. Prowell TM, Pazdur R. Pathological complete response and accelerated drug approval in early breast cancer. N Engl J Med 2012;366: 2438-41.