Targeting a common collaborator in cancer development

Science Translational Medicine

Volumn 2, Issue 48, 2010, Pages

  Myers, Andrea P ^a,b   Cantley, Lewis C ^b,c  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (1H INDAZOL 4 YL) 6 (4 METHANESULFONYL 1 PIPERAZINYLMETHYL) 4 MORPHOLINOTHIENO[3,2 D]PYRIMIDINE; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 PHOSPHATE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; 2 (1H INDAZOL 4 YL) 6 (4 METHANESULFONYLPIPERAZIN 1 YLMETHYL) 4 MORPHOLIN 4 YLTHIENO(3,2 D)PYRIMIDINE; 2-(1H-INDAZOL-4-YL)-6-(4-METHANESULFONYLPIPERAZIN-1-YLMETHYL)-4-MORPHOLIN-4-YLTHIENO(3,2-D)PYRIMIDINE; ANTINEOPLASTIC ANTIBIOTIC; INDAZOLE DERIVATIVE; SULFONAMIDE; TUMOR MARKER;

ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER CELL; CANCER COMBINATION CHEMOTHERAPY; CELL CYCLE ARREST; DNA DAMAGE; DRUG DESIGN; DRUG DETERMINATION; DRUG POTENTIATION; DRUG SAFETY; DRUG TARGETING; GENE ACTIVITY; GENE AMPLIFICATION; GENE MUTATION; HUMAN; KIDNEY CARCINOMA; NONHUMAN; OVARY CANCER; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TRANSLATIONAL RESEARCH; DRUG ANTAGONISM; DRUG EFFECT; NEOPLASM; NOTE; PATHOPHYSIOLOGY; TUMOR CELL LINE;

ANTIBIOTICS, ANTINEOPLASTIC; CELL LINE, TUMOR; DOXORUBICIN; DRUG SYNERGISM; HUMANS; INDAZOLES; NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASE; SULFONAMIDES; TUMOR MARKERS, BIOLOGICAL;

EID: 77956573234     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3001251     Document Type: Review

References (30)

1. J. J. Wallin, J. Guan, W. W. Prior, K. A. Edgar, R. Kassees, D. Sampath, M. Belvin, L. S. Friedman, Nuclear phosphoAkt increase predicts synergy of PI3K inhibition and doxorubicin in breast and ovarian cancer. Sci. Transl. Med. 2, 48ra66 (2010).
2. A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, M. J. Thun, Cancer statistics, 2009. CA Cancer J. Clin. 59, 225-249 (2009).
3. J. A. Engelman, J. Luo, L. C. Cantley, The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat. Rev. Genet. 7, 606-619 (2006).
4. T. L. Yuan, L. C. Cantley, PI3K pathway alterations in cancer: Variations on a theme. Oncogene 27, 5497-5510 (2008).
5. A. Carracedo, P. P. Pandolfi, the PTEN-PI3K pathway: Of feedbacks and cross-talks. Oncogene 27, 5527-5541 (2008).
6. D. J. Slamon, G. M. Clark, S. G. Wong, W. J. Levin, A. Ullrich, W. L. McGuire, Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177-182 (1987).
7. Y. Samuels, Z. Wang, A. Bardelli, N. Silliman, J. Ptak, S. Szabo, H. Yan, A. Gazdar, S. M. Powell, G. J. Riggins, J. K. V. Willson, S. Markowitz, K. W. Kinzler, B. Vogelstein, V. E. Velculescu, High frequency of mutations of the PIK3CA gene in human cancers. Science 304, 554 (2004).
8. I. G. Campbell, S. E. Russell, D. Y. Choong, K. G. Montgomery, M. L. Ciavarella, C. S. Hooi, B. E. Cristiano, R. B. Pearson, W. A. Phillips, Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res. 64, 7678-7681 (2004).
9. S. A. Forbes, G. Bhamra, S. Bamford, E. Dawson, C. Kok, J. Clements, A. Menzies, J. W. Teague, P. A. Futreal, M. R. Stratton, The catalogue of somatic mutations in cancer (COSMIC). Curr. Protoc. Hum. Genet. Chapter 10, p. Unit 10.11 (2008).
10. J. Li, C. Yen, D. Liaw, K. Podsypanina, S. Bose, S. I. Wang, J. Puc, C. Miliaresis, L. Rodgers, R. McCombie, S. H. Bigner, B. C. Giovanella, M. Ittmann, B. Tycko, H. Hibshoosh, M. H. Wigler, R. Parsons, PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275, 1943-1947 (1997).
11. M. Sun, J. E. Paciga, R. I. Feldman, Z. Yuan, D. Coppola, Y. Y. Lu, S. A. Shelley, S. V. Nicosia, J. Q. Cheng, Phosphatidylinositol-3-OH kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor α (ERalpha) via interaction between ERalpha and PI3K. Cancer Res. 61, 5985-5991 (2001).
12. K. Nakayama, N. Nakayama, R. J. Kurman, L. Cope, G. Pohl, Y. Samuels, V. E. Velculescu, T. L. Wang, I.-M. Shih, Sequence mutations and amplification of PIK3CA and AKT2 genes in purified ovarian serous neoplasms. Cancer Biol. Ther. 5, 779-785 (2006).
13. C. Gewinner, Z. C. Wang, A. Richardson, J. Teruya-Feldstein, D. Etemadmoghadam, D. Bowtell, J. Barretina, W. M. Lin, L. Rameh, L. Salmena, P. P. Pandolfi, L. C. Cantley, Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling. Cancer Cell 16, 115-125 (2009).
14. J. A. Engelman, Targeting PI3K signalling in cancer: Opportunities, challenges and limitations. Nat. Rev. Cancer 9, 550-562 (2009).
15. K. D. Courtney, R. B. Corcoran, J. A. Engelman, The PI3K pathway as drug target in human cancer. J. Clin. Oncol. 28, 1075-1083 (2010).
16. D. D. Von Hoff, P. Lorusso, R. Tibes, G. Shapiro, G. J. Weiss, J. A. Ware, J. Fredrickson, K. E. Mazina, G. G. Levy, A. J. Wagner, A first-in-human phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumors. J. Clin. Oncol. 28:15s, 2541 (2010).
17. J. Baselga, M. J. De Jonge, J. Rodon, H. A. Burris III, D. C. Birle, S. S. De Buck, D. Demanse, Q. C. Ru, M. Goldbrunner, J. C. Bendell, A first-in-human phase I study of BKM120, an oral pan-class I PI3K inhibitor, in patients (pts) with advanced solid tumors. J. Clin. Oncol. 28:15s, 3003 (2010).
18. See the U.S. National Institutes of Health clinical trials Web site, http://clinicaltrials.gov.
19. R. D. Mass, M. F. Press, S. Anderson, M. A. Cobleigh, C. L. Vogel, N. Dybdal, G. Leiberman, D. J. Slamon, Evaluation of clinical outcomes according to HER2 detection by fluorescence in situ hybridization in women with metastatic breast cancer treated with trastuzumab. Clin. Breast Cancer 6, 240-246 (2005).
20. N. L. Henry, D. F. Hayes, Uses and abuses of tumor markers in the diagnosis, monitoring, and treatment of primary and metastatic breast cancer. Oncologist 11, 541-552 (2006).
21. J. Baselga, D. Tripathy, J. Mendelsohn, S. Baughman, C. C. Benz, L. Dantis, N. T. Sklarin, A. D. Seidman, C. A. Hudis, J. Moore, P. P. Rosen, T. Twaddell, I. C. Henderson, L. Norton, Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J. Clin. Oncol. 14, 737-744 (1996).
22. M. D. Pegram, A. Lipton, D. F. Hayes, B. L. Weber, J. M. Baselga, D. Tripathy, D. Baly, S. A. Baughman, T. Twaddell, J. A. Glaspy, D. J. Slamon, Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J. Clin. Oncol. 16, 2659-2671 (1998).
23. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, Breast Cancer V.2.2010; available at www.nccn.org/professionals/ physician-gls/f-guidelines.asp.
24. Q. B. She, S. Chandarlapaty, Q. Ye, J. Lobo, K. M. Haskell, K. R. Leander, D. DeFeo-Jones, H. E. Huber, N. Rosen, T. Ouchi, Breast tumor cells with PI3K mutation or HER2 amplification are selectively addicted to Akt signaling. PLoS ONE 3, e3065 (2008).
25. J. A. Engelman, L. Chen, X. Tan, K. Crosby, A. R. Guimaraes, R. Upadhyay, M. Maira, K. McNamara, S. A. Perera, Y. Song, L. R. Chirieac, R. Kaur, A. Lightbown, J. Simendinger, T. Li, R. F. Padera, C. García- Echeverría, R. Weissleder, U. Mahmood, L. C. Cantley, K. K. Wong, Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat. Med. 14, 1351-1356 (2008).
26. H. Burris, J. Rodon, S. Sharma, R. S. Herbst, J. Tabernero, First-in-human phase I study of the oral PI3K inhibitor BEZ235 in patients with advanced solid tumors. J. Clin. Oncol. 28:15s 3005 (2010).
27. G. Edelman, C. Bedell, G. Shapiro, S. S. Pandya, E. L. Kwak, C. Scheffold, L. T. Nguyen, A. Laird, J. Baselga, J. Rodon, A phase I dose-escalation study of XL147 (SAR245408), a PI3K inhibitor administered orally to patients (pts) with advanced malignancies. J. Clin. Oncol. 28:15s, 3004 (2010).
28. T. A. Yap, A. Patnaik, I. Fearen, D. Olmos, K. Papadopoulos, N. Tunariu, D. Sullivan, L. Yan, J. S. De Bono, A. W. Tolcher, First-in-class phase I trial of a selective Akt inhibitor, MK2206 (MK), evaluating alternate day (QOD) and once weekly (QW) doses in advanced cancer patients (pts) with evidence of target modulation and antitumor activity. J. Clin. Oncol. 28:15s, 3009 (2010)
29. A. Carracedo, L. Ma, J. Teruya-Feldstein, F. Rojo, L. Salmena, A. Alimonti, A. Egia, A. T. Sasaki, G. Thomas, S. C. Kozma, A. Papa, C. Nardella, L. C. Cantley, J. Baselga, P. P. Pandolfi, Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J. Clin. Invest. 118, 3065-3074 (2008).
30. Funding: The authors acknowledge the Stand Up To Cancer Foundation, the National Institutes of Health, and the Dana-Farber/Harvard Cancer Center for grant support to study the PI3K pathway in women's cancers. A.P.M. also receives funding from the Dana-Farber/Harvard Cancer Center. Competing interests: L.C.C. has consulted for companies that are generating PI3K pathway inhibitors, including Genentech, Novartis, GlaxoSmithKline, Bristol-Myers Squibb, and AstraZeneca. A.P.M. declares that she has no competing interests.