Rational selection of biomarker driven therapies for gynecologic cancers: The more we know, the more we know we don't know

Gynecologic Oncology

Volumn 141, Issue 1, 2016, Pages 65-71

  Liu, Joyce ^a   Westin, Shannon N ^b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Biomarkers; Gynecologic cancer; Personalized medicine; Precision medicine; Targeted therapy

Indexed keywords

ANGIOGENESIS INHIBITOR; BIOLOGICAL MARKER; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; ONCOPROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN P53; B RAF KINASE; BRAF PROTEIN, HUMAN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; TUMOR MARKER;

ANGIOGENESIS; ARTICLE; CANCER IMMUNOTHERAPY; CANCER THERAPY; DNA SEQUENCE; ENZYME INHIBITION; FEMALE; FEMALE GENITAL TRACT CANCER; HUMAN; PRIORITY JOURNAL; RETROVIRIDAE; SIGNAL TRANSDUCTION; ANTAGONISTS AND INHIBITORS; GENETICS; GENITAL NEOPLASMS, FEMALE; IMMUNOTHERAPY; MOLECULARLY TARGETED THERAPY; MUTATION; PERSONALIZED MEDICINE; TUMOR SUPPRESSOR GENE;

BIOMARKERS, TUMOR; FEMALE; GENES, BRCA1; GENES, P53; GENITAL NEOPLASMS, FEMALE; HUMANS; IMMUNOTHERAPY; MOLECULAR TARGETED THERAPY; MUTATION; PHOSPHATIDYLINOSITOL 3-KINASES; POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; PRECISION MEDICINE; PROTO-ONCOGENE PROTEINS B-RAF;

EID: 84961837934     PISSN: 00908258     EISSN: 10956859     Source Type: Journal    
DOI: 10.1016/j.ygyno.2016.01.003     Document Type: Article

References (97)

1. D. Hanahan, and R.A. Weinberg Hallmarks of cancer: the next generation Cell 144 5 2011 646 674
2. B.J. Druker, M. Talpaz, D.J. Resta, B. Peng, E. Buchdunger, J.M. Ford, and et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia N. Engl. J. Med. 344 14 2001 1031 1037
3. F.A. Shepherd, J. Rodrigues Pereira, T. Ciuleanu, E.H. Tan, V. Hirsh, S. Thongprasert, and et al. Erlotinib in previously treated non-small-cell lung cancer N. Engl. J. Med. 353 2 2005 123 132
4. M.S. Tsao, A. Sakurada, J.C. Cutz, C.Q. Zhu, S. Kamel-Reid, J. Squire, and et al. Erlotinib in lung cancer - molecular and clinical predictors of outcome N. Engl. J. Med. 353 2 2005 133 144
5. J.R. Westin Busting robustness: using cancer's greatest strength to our advantage Future Oncol. 11 1 2015 73 77
6. G. Getz, S.B. Gabriel, K. Cibulskis, E. Lander, A. Sivachenko, C. Sougnez, and et al. Integrated genomic characterization of endometrial carcinoma Nature 497 7447 2013 67 73
7. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609-15.
8. A.I. Ojesina, L. Lichtenstein, S.S. Freeman, C.S. Pedamallu, I. Imaz-Rosshandler, T.J. Pugh, and et al. Landscape of genomic alterations in cervical carcinomas Nature 506 7488 2014 371 375
9. A. de Gramont, S. Watson, L.M. Ellis, J. Rodon, J. Tabernero, A. de Gramont, and et al. Pragmatic issues in biomarker evaluation for targeted therapies in cancer Nat. Rev. Clin. Oncol. 12 4 2015 197 212
10. A.N. Weaver, and E.S. Yang Beyond DNA repair: additional functions of PARP-1 in cancer Front Oncol. 3 2013 290
11. H. Farmer, N. McCabe, C.J. Lord, A.N. Tutt, D.A. Johnson, T.B. Richardson, and et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy Nature 434 7035 2005 917 921
12. T. Helleday, H.E. Bryant, and N. Schultz Poly(ADP-ribose) polymerase (PARP-1) in homologous recombination and as a target for cancer therapy Cell Cycle 4 9 2005 1176 1178
13. M.W. Audeh, J. Carmichael, R.T. Penson, M. Friedlander, B. Powell, K.M. Bell-McGuinn, and et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial Lancet 376 9737 2010 245 251
14. R.L. Coleman, M.W. Sill, K. Bell-McGuinn, C. Aghajanian, H.J. Gray, K.S. Tewari, and et al. A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation - an NRG Oncology/Gynecologic Oncology Group study Gynecol. Oncol. 137 3 2015 386 391
15. J. Ledermann, P. Harter, C. Gourley, M. Friedlander, I. Vergote, G. Rustin, and et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer N. Engl. J. Med. 366 15 2012 1382 1392
16. J. Ledermann, P. Harter, C. Gourley, M. Friedlander, I. Vergote, G. Rustin, and et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial Lancet Oncol. 15 8 2014 852 861
17. K.P. Pennington, T. Walsh, M.I. Harrell, M.K. Lee, C.C. Pennil, M.H. Rendi, and et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas Clin. Cancer Res. 20 3 2014 764 775
18. K.A. Gelmon, M. Tischkowitz, H. Mackay, K. Swenerton, A. Robidoux, K. Tonkin, and et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study The Lancet Oncology. 12 9 2011 852 861
19. I.A. McNeish, A.M. Oza, R.L. Coleman, C.L. Scott, G.E. Konecny, A. Tinker, and et al. Results of ARIEL2: a phase 2 trial to prospectively identify ovarian cancer patients likely to respond to rucaparib using tumor genetic analysis J. Clin. Oncol. 33 Suppl; abstr 5508 2015
20. E. Swisher, A.M. Oza, R.L. Coleman, C. Scott, K. Lin, E. Dominy, and et al. Tumor BRCA mutation or high genomic LOH identify ovarian cancer patients likely to respond to rucaparib: interim results for ARIEL2 clinical trial Gynecol. Oncol. 138 Supplement 1 2015 4
21. C.L. Scott, E.M. Swisher, and S.H. Kaufmann Poly (ADP-ribose) polymerase inhibitors: recent advances and future development J. Clin. Oncol. 33 12 2015 1397 1406
22. C. Kandoth, N. Schultz, A.D. Cherniack, R. Akbani, Y. Liu, H. Shen, and et al. Integrated genomic characterization of endometrial carcinoma Nature 497 7447 2013 67 73
23. A.M. Mendes-Pereira, S.A. Martin, R. Brough, A. McCarthy, J.R. Taylor, J.S. Kim, and et al. Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors EMBO Molecular Medicine. 1 6-7 2009 315 322
24. K.J. Dedes, D. Wetterskog, A.M. Mendes-Pereira, R. Natrajan, M.B. Lambros, F.C. Geyer, and et al. PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors Sci. Transl. Med. 2 53 2010 53ra75
25. M.D. Forster, K.J. Dedes, S. Sandhu, S. Frentzas, R. Kristeleit, A. Ashworth, and et al. Treatment with olaparib in a patient with PTEN-deficient endometrioid endometrial cancer Nat Rev Clin Oncol. 8 5 2011 302 306
26. L. Shunkwiler, G. Ferris, and C. Kunos Inhibition of poly(ADP-ribose) polymerase enhances radiochemosensitivity in cancers proficient in DNA double-strand break repair Int. J. Mol. Sci. 14 2 2013 3773 3785
27. R.A. Burger, M.W. Sill, B.J. Monk, B.E. Greer, and J.I. Sorosky Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group study J. Clin. Oncol. 25 33 2007 5165 5171
28. S.A. Cannistra, U.A. Matulonis, R.T. Penson, J. Hambleton, J. Dupont, H. Mackey, and et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer J. Clin. Oncol. 25 33 2007 5180 5186
29. U.A. Matulonis, S. Berlin, P. Ivy, K. Tyburski, C. Krasner, C. Zarwan, and et al. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer J. Clin. Oncol. 27 33 2009 5601 5606
30. H. Hirte, S. Lheureux, G.F. Fleming, A. Sugimoto, R. Morgan, J. Biagi, and et al. A phase 2 study of cediranib in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: a trial of the Princess Margaret, Chicago and California Phase II Consortia Gynecol. Oncol. 138 1 2015 55 61
31. R.A. Burger, M.F. Brady, M.A. Bookman, G.F. Fleming, B.J. Monk, H. Huang, and et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer N. Engl. J. Med. 365 26 2011 2473 2483
32. T.J. Perren, A.M. Swart, J. Pfisterer, J.A. Ledermann, E. Pujade-Lauraine, G. Kristensen, and et al. A phase 3 trial of bevacizumab in ovarian cancer N. Engl. J. Med. 365 26 2011 2484 2496
33. A. du Bois, J. Huober, P. Stopfer, J. Pfisterer, P. Wimberger, S. Loibl, and et al. A phase I open-label dose-escalation study of oral BIBF 1120 combined with standard paclitaxel and carboplatin in patients with advanced gynecological malignancies Ann. Oncol. 21 2 2010 370 375
34. C. Aghajanian, S.V. Blank, B.A. Goff, P.L. Judson, M.G. Teneriello, A. Husain, and et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer J. Clin. Oncol. 30 17 2012 2039 2045
35. J.A. Ledermann, F.A. Raja, A. Embleton, G.J.S. Rustin, G. Jayson, and S.B. Kaye Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: results of the ICON6 trial Eur. J. Cancer 49 Suppl 3: LBA 10 2013
36. E. Pujade-Lauraine, F. Hilpert, B. Weber, A. Reuss, G. Kristensen, R. Sorio, and et al. AURELIA: a randomized phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant ovarian cancer (OC) J. Clin. Oncol. 30 Suppl; abstr LBA5002 2012
37. R.L. Coleman, M.F. Brady, T.J. Herzog, P. Sabbatini, D.K. Armstrong, J.L. Walker, and et al. A phase III randomized controlled clinical trial of carboplatin and paclitaxel alone or in combination with bevacizumab followed by bevacizumab and secondary cytoreductive surgery in platinum-sensitive, recurrent ovarian, peritoneal primary and fallopian tube cancer (Gynecologic Oncology Group 0213) Gynecol. Oncol. 137 Supplement 1 2015 3 4
38. C. Aghajanian, M.W. Sill, K.M. Darcy, B. Greer, D.S. McMeekin, P.G. Rose, and et al. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group Study J. Clin. Oncol. 29 16 2011 2259 2265
39. C. Aghajanian, V.L. Filiaci, D.S. Dizon, J.W. Carlson, M.A. Powell, A.A. Secord, and et al. A randomized phase II study of paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus and ixabepilone/carboplatin/bevacizumab as initial therapy for measurable stage III or IVA, stage IVB or recurrent endometrial cancer, GOG-86P J. Clin. Oncol. 33 Suppl; abstr 5500 2015
40. D. Lorusso, G. Ferrandina, N. Colombo, S. Pignata, V. Salutari, G. Maltese, and et al. Randomized phase II trial of carboplatin-paclitaxel (CP) compared to carboplatin-paclitaxel-bevacizumab (CP-B) in advanced (stage III-IV) or recurrent endometrial cancer: the MITO END-2 trial J. Clin. Oncol. 33 Suppl; abstr 5502 2015
41. K.S. Tewari, M.W. Sill, H.J. Long 3rd, R.T. Penson, H. Huang, L.M. Ramondetta, and et al. Improved survival with bevacizumab in advanced cervical cancer N. Engl. J. Med. 370 8 2014 734 743
42. C. Gourley, A. McCavigan, T. Perren, J. Paul, C.O. Michie, M. Churchman, and et al. Molecular subgroup of high-grade serous ovarian cancer (HGSOC) as a predictor of outcome following bevacizumab J. Clin. Oncol. 32 5s (Suppl; abstr 5502) 2014
43. B.J.N. Winterhoff, S. Kommoss, A.L. Oberg, C. Wang, S.M. Riska, G.E. Konecny, and et al. Bevacizumab and improvement of progression-free survival (PFS) for patients with the mesenchymalmolecular subtype of ovarian cancer J. Clin. Oncol. 32 5s (Suppl; abstr 5509) 2014
44. M.J. Birrer, Y.J. Choi, M.F. Brady, R.S. Mannel, R.A. Burger, W. Wei, and et al. Retrospective analysis of candidate predictive tumor biomarkers (BMs) for efficacy in the GOG-0218 trial evaluating front-line carboplatin-paclitaxel (CP) ± bevacizumab (BEV) for epithelial ovarian cancer (EOC) J. Clin. Oncol. 33 Suppl; abstr 5505 2015
45. K.S. Tewari, M. Sill, B.J. Monk, R.T. Penson, H.A. Lankes, M.M. Leitao, and et al. Impact of circulating tumor cells (CTCs) on overall survival among patients treated with chemotherapy plus bevacizumab for advanced cervical cancer: an NRG Oncology/Gynecologic Oncology Group study Gynecol. Oncol. 137 Supplement 1 2015 12
46. Y. Samuels, Z. Wang, A. Bardelli, N. Silliman, J. Ptak, S. Szabo, and et al. High frequency of mutations of the PIK3CA gene in human cancers Science 304 5670 2004 554
47. Bartlett JM. Biomarkers and patient selection for PI3K/Akt/mTOR targeted therapies: current status and future directions. Clin Breast Cancer.10 Suppl 3:S86-95.
48. K. Oda, D. Stokoe, Y. Taketani, and F. McCormick High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma Cancer Res. 65 23 2005 10669 10673
49. R.M. Bigsby, A.X. Li, J. Bomalaski, F.B. Stehman, K.Y. Look, and G.P. Sutton Immunohistochemical study of HER-2/neu, epidermal growth factor receptor, and steroid receptor expression in normal and malignant endometrium Obstet. Gynecol. 79 1 1992 95 100
50. A. Dutt, H.B. Salvesen, H. Greulich, W.R. Sellers, R. Beroukhim, and M. Meyerson Somatic mutations are present in all members of the AKT family in endometrial carcinoma Br. J. Cancer 101 7 2009 1218 1219 (author reply 20-1)
51. A. Dutt, H.B. Salvesen, T.H. Chen, A.H. Ramos, R.C. Onofrio, C. Hatton, and et al. Drug-sensitive FGFR2 mutations in endometrial carcinoma Proc. Natl. Acad. Sci. U. S. A. 105 25 2008 8713 8717
52. J.L. Hecht, and G.L. Mutter Molecular and pathologic aspects of endometrial carcinogenesis J. Clin. Oncol. 24 29 2006 4783 4791
53. K. Shoji, K. Oda, S. Nakagawa, S. Hosokawa, G. Nagae, Y. Uehara, and et al. The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas Br. J. Cancer 101 1 2009 145 148
54. A.M. Oza, L. Elit, M.S. Tsao, S. Kamel-Reid, J. Biagi, D.M. Provencher, and et al. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group J. Clin. Oncol. 29 24 2011 3278 3285
55. I. Ray-Coquard, L. Favier, B. Weber, C. Roemer-Becuwe, P. Bougnoux, M. Fabbro, and et al. Everolimus as second- or third-line treatment of advanced endometrial cancer: ENDORAD, a phase II trial of GINECO Br. J. Cancer 108 9 2013 1771 1777
56. B.M. Slomovitz, K.H. Lu, T. Johnston, R.L. Coleman, M. Munsell, R.R. Broaddus, and et al. A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma Cancer 2010
57. A.P. Myers, R. Broaddus, V. Makker, P. Konstantinopoulos, R. Drapkin, N.S. Horowitz, and et al. Phase II, two-stage, two-arm, PIK3CA mutation stratified trial of MK-2206 in recurrent endometrial cancer J. Clin. Oncol. 31 Suppl; abstr 5524 2013
58. D. Tsoref, S. Welch, S. Lau, J. Biagi, K. Tonkin, L.A. Martin, and et al. Phase II study of oral ridaforolimus in women with recurrent or metastatic endometrial cancer Gynecol. Oncol. 135 2 2014 184 189
59. K.E. O'Reilly, F. Rojo, Q.B. She, D. Solit, G.B. Mills, D. Smith, and et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt Cancer Res. 66 3 2006 1500 1508
60. H.J. Mackay, E.A. Eisenhauer, S. Kamel-Reid, M. Tsao, B. Clarke, K. K, and et al. Molecular determinants of outcome with mammalian target of rapamycin inhibition in endometrial cancer Cancer 120 4 2014 603 610
61. L.A. Meyer, B.M. Slomovitz, B. Djordjevic, S.N. Westin, D.A. Iglesias, M.F. Munsell, and et al. The search continues: looking for predictive biomarkers for response to mammalian target of rapamycin inhibition in endometrial cancer Int. J. Gynecol. Cancer 24 4 2014 713 717
62. D.A. Altomare, H.Q. Wang, K.L. Skele, A. De Rienzo, A.J. Klein-Szanto, A.K. Godwin, and et al. AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth Oncogene 23 34 2004 5853 5857
63. K. Behbakht, M.W. Sill, K.M. Darcy, S.C. Rubin, R.S. Mannel, S. Waggoner, and et al. Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study Gynecol. Oncol. 123 1 2011 19 26
64. A.M. Traynor, R. Kurzrock, H.H. Bailey, S. Attia, C. Scheffold, B. van Leeuwen, and et al. A phase I safety and pharmacokinetic (PK) study of the PI3K inhibitor XL147 (SAR245408) in combination with paclitaxel (P) and carboplatin (C) in patients (pts) with advanced solid tumors J. Clin. Oncol. 28 15s (Suppl; abstr 3078) 2010
65. E.R. King, Z. Zu, Y.T. Tsang, M.T. Deavers, A. Malpica, S.C. Mok, and et al. The insulin-like growth factor 1 pathway is a potential therapeutic target for low-grade serous ovarian carcinoma Gynecol. Oncol. 123 1 2011 13 18
66. M. Mazzoletti, and M. Broggini PI3K/AKT/mTOR inhibitors in ovarian cancer Curr. Med. Chem. 17 36 2010 4433 4447
67. Y. Wang, A. Helland, R. Holm, G.B. Kristensen, and A.L. Borresen-Dale PIK3CA mutations in advanced ovarian carcinomas Hum. Mutat. 25 3 2005 322
68. F. Zagouri, T.N. Sergentanis, D. Chrysikos, M. Filipits, and R. Bartsch Molecularly targeted therapies in cervical cancer. A systematic review Gynecol. Oncol. 126 2 2012 291 303
69. A.A. Wright, B.E. Howitt, A.P. Myers, S.E. Dahlberg, E. Palescandolo, P. Van Hummelen, and et al. Oncogenic mutations in cervical cancer: genomic differences between adenocarcinomas and squamous cell carcinomas of the cervix Cancer 119 21 2013 3776 3783
70. A.V. Tinker, S. Ellard, S. Welch, F. Moens, G. Allo, M.S. Tsao, and et al. Phase II study of temsirolimus (CCI-779) in women with recurrent, unresectable, locally advanced or metastatic carcinoma of the cervix. A trial of the NCIC Clinical Trials Group (NCIC CTG IND 199) Gynecol. Oncol. 130 2 2013 269 274
71. N.G. Ahn, T.S. Nahreini, N.S. Tolwinski, and K.A. Resing Pharmacologic inhibitors of MKK1 and MKK2 Methods Enzymol. 332 2001 417 431
72. S.L. Abrams, L.S. Steelman, J.G. Shelton, E.W. Wong, W.H. Chappell, J. Basecke, and et al. The Raf/MEK/ERK pathway can govern drug resistance, apoptosis and sensitivity to targeted therapy Cell Cycle 9 9 2010 1781 1791
73. R. Dummer, C. Robert, P.B. Chapman, J.A. Sosman, M. Middleton, L. Bastholt, and et al. AZD6244 (ARRY-142886) vs temozolomide (TMZ) in patients (pts) with advanced melanoma: An open-label, randomized, multicenter, phase II study J. Clin. Oncol. 26 Suppl; abstr 9033 2008
74. S.P. Patel, A.J. Lazar, S. Mahoney, C. Vaughn, N. Gonzalez, N.E. Papadopoulos, and et al. Clinical responses to AZD6244 (ARRY-142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma ASCO Molecular Markers 2010 2010
75. B.B. Friday, and A.A. Adjei Advances in targeting the Ras/Raf/MEK/Erk mitogen-activated protein kinase cascade with MEK inhibitors for cancer therapy Clin. Cancer Res. 14 2 2008 342 346
76. M.S. Chapman, and J.N. Miner Novel mitogen-activated protein kinase kinase inhibitors Expert Opin Investig Drugs. 20 2 2011 209 220
77. K.K. Wong, Y.T. Tsang, M.T. Deavers, S.C. Mok, Z. Zu, C. Sun, and et al. BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas Am J Pathol. 177 4 2010 1611 1617
78. R.N. Grisham, G. Iyer, K. Garg, D. DeLair, D.M. Hyman, Q. Zhou, and et al. BRAF mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer Cancer 119 3 2013 548 554
79. Y.T. Tsang, M.T. Deavers, C.C. Sun, S.Y. Kwan, E. Kuo, A. Malpica, and et al. KRAS (but not BRAF) mutations in ovarian serous borderline tumour are associated with recurrent low-grade serous carcinoma J. Pathol. 231 4 2013 449 456
80. J. Farley, W.E. Brady, V. Vathipadiekal, H.A. Lankes, R. Coleman, M.A. Morgan, and et al. Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study Lancet Oncol. 14 2 2013 134 140
81. G. Singer, R. Oldt 3rd, Y. Cohen, B.G. Wang, D. Sidransky, R.J. Kurman, and et al. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma J. Natl. Cancer Inst. 95 6 2003 484 486
82. A. Koul, R. Willen, P.O. Bendahl, M. Nilbert, and A. Borg Distinct sets of gene alterations in endometrial carcinoma implicate alternate modes of tumorigenesis Cancer 94 9 2002 2369 2379
83. R. Coleman, M. Sill, P.H. Thaker, K. De Geest, D. Street, W. McGuire, and et al. A phase II evaluation of AZD6244, a selective MEK-1/2 inhibitor in the treatment of recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study Gynecol. Oncol. 130 1 2013 e12 e13
84. M.A. Khalifa, R.S. Mannel, S.D. Haraway, J. Walker, and K.W. Min Expression of EGFR, HER-2/neu, P53, and PCNA in endometrioid, serous papillary, and clear cell endometrial adenocarcinomas Gynecol. Oncol. 53 1 1994 84 92
85. A. Oza, J.I. Weberpals, D.M. Provencher, E.-M. Grischke, M. Hall, D. Uyar, and et al. An international, biomarker-directed, randomized, phase II trial of AZD1775 plus paclitaxel and carboplatin (P/C) for the treatment of women with platinum-sensitive, TP53-mutant ovarian cancer J. Clin. Oncol. 33 Suppl; abstr 5506 2015
86. Z. Wang, and Y. Sun Targeting p53 for novel anticancer therapy Transl. Oncol. 3 1 2010 1 12
87. E.L. Smith, D. Zamarin, and A.M. Lesokhin Harnessing the immune system for cancer therapy Curr. Opin. Oncol. 26 6 2014 600 607
88. S.L. Topalian, F.S. Hodi, J.R. Brahmer, S.N. Gettinger, D.C. Smith, D.F. McDermott, and et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer N. Engl. J. Med. 366 26 2012 2443 2454
89. E.B. Garon, N.A. Rizvi, R. Hui, N. Leighl, A.S. Balmanoukian, J.P. Eder, and et al. Pembrolizumab for the treatment of non-small-cell lung cancer N. Engl. J. Med. 372 21 2015 2018 2028
90. C. Robert, G.V. Long, B. Brady, C. Dutriaux, M. Maio, L. Mortier, and et al. Nivolumab in previously untreated melanoma without BRAF mutation N. Engl. J. Med. 372 4 2015 320 330
91. R.J. Motzer, B.I. Rini, D.F. McDermott, B.G. Redman, T.M. Kuzel, M.R. Harrison, and et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial J. Clin. Oncol. 33 13 2015 1430 1437
92. J. Hamanishi, M. Mandai, T. Ikeda, M. Minami, A. Kawaguchi, T. Murayama, and et al. Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer J. Clin. Oncol. 2015;Sept 8 (epub ahead of print)
93. M.L. Disis, M.R. Patel, S. Pant, J.R. Infante, A.C. Lockhart, K. Kelly, and et al. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with previously treated, recurrent or refractory ovarian cancer: a phase Ib, open-label expansion trial J. Clin. Oncol. 33 Suppl; abstr 5509 2015
94. A. Varga, S.A. Piha-Paul, P.A. Ott, J.M. Mehnert, D. Berton-Rigaud, E.A. Johnson, and et al. Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: interim results from a phase Ib study J. Clin. Oncol. 33 Suppl; abstr 5510 2015
95. K. Strickland, B.E. Howitt, S.J. Rodig, L. Ritterhouse, A.D. D'Andrea, U. Matulonis, and et al. Tumor infiltrating and peritumoral T cells and expression of PD-L1 in BRCA1/2-mutated high grade serous ovarian cancers J. Clin. Oncol. 33 Suppl abstr 5512 2015
96. B.E. Howitt, L.M. Sholl, L. Ritterhouse, J.C. Watkins, S.J. Rodig, K. Strickland, and et al. Association of POLE-mutated and MSI endometrial cancers with an elevated number of tumor-infiltrating and peritumoral lymphocytes and higher expression of PD-L1 J. Clin. Oncol. 33 Suppl; abstr 5511 2015
97. D.T. Le, J.N. Uram, H. Wang, B.R. Bartlett, H. Kemberling, A.D. Eyring, and et al. PD-1 blockade in tumors with mismatch-repair deficiency N. Engl. J. Med. 372 26 2015 2509 2520