J Korean Med Assoc.  2016 Mar;59(3):189-193. 10.5124/jkma.2016.59.3.189.

Current trend in translational research for treatment of ovarian cancer

• Ju W

• KMID: 2382723
• DOI: http://doi.org/10.5124/jkma.2016.59.3.189

Abstract

Ovarian cancer is the most lethal gynecologic cancer. Countless efforts have been made to improve the survival of ovarian cancer patients by clinicians as well as basic researchers so far. As a result of those extensive translational researches some of promising molecular targets and its proper therapies are introduced into practice for treating intractable ovarian cancer, which includes anti-angiogenic therapy, tyrosine kinase inhibitor, and other modulators of cancer-related signaling pathways. Current trend of translational researches in ovarian cancer treatment are mainly focused on discovering companion diagnostics which can categorize the subgroup of patient having specific biomarker that may serve as a target of new treatment because the consequent outcome of new therapy varies depending on the molecular profile of each patient. It is important for clinician to consider each ovarian cancer patients to have a possible therapeutic target and to examine the tissue biopsies with available companion diagnostics. In addition more interest and endeavor should be given to the clinical trials to apply the result of up-to-date translational researches.

Keyword

Ovarian neoplasms; Translational medical research; Companion diagnostics

MeSH Terms

Biopsy
Friends
Humans
Ovarian Neoplasms*
Protein-Tyrosine Kinases
Translational Medical Research*
Protein-Tyrosine Kinases

Reference

1. Sankaranarayanan R, Ferlay J. Worldwide burden of gynaecological cancer: the size of the problem. Best Pract Res Clin Obstet Gynaecol. 2006; 20:207–225.

2. Gershenson DM, Sun CC, Bodurka D, Coleman RL, Lu KH, Sood AK, Deavers M, Malpica AL, Kavanagh JJ. Recurrent low-grade serous ovarian carcinoma is relatively chemoresistant. Gynecol Oncol. 2009; 114:48–52.

3. Li J, Fadare O, Xiang L, Kong B, Zheng W. Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis. J Hematol Oncol. 2012; 5:8.

4. Farley J, Brady WE, Vathipadiekal V, Lankes HA, Coleman R, Morgan MA, Mannel R, Yamada SD, Mutch D, Rodgers WH, Birrer M, Gershenson DM. Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study. Lancet Oncol. 2013; 14:134–140.

5. Gershenson DM. The life and times of low-grade serous carcinoma of the ovary. Am Soc Clin Oncol Educ Book. 2013; [Epub]. DOI: 10.1200/EdBook_AM.2013.33.e195.

6. Kojima K, Konopleva M, McQueen T, O'Brien S, Plunkett W, Andreeff M. Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia. Blood. 2006; 108:993–1000.

7. Madhusudan S, Muthuramalingam SR, Braybrooke JP, Wilner S, Kaur K, Han C, Hoare S, Balkwill F, Ganesan TS. Study of etanercept, a tumor necrosis factor-alpha inhibitor, in recurrent ovarian cancer. J Clin Oncol. 2005; 23:5950–5959.

8. Brown ER, Charles KA, Hoare SA, Rye RL, Jodrell DI, Aird RE, Vora R, Prabhakar U, Nakada M, Corringham RE, DeWitte M, Sturgeon C, Propper D, Balkwill FR, Smyth JF. A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer. Ann Oncol. 2008; 19:1340–1346.

9. Coward J, Kulbe H, Chakravarty P, Leader D, Vassileva V, Leinster DA, Thompson R, Schioppa T, Nemeth J, Vermeulen J, Singh N, Avril N, Cummings J, Rexhepaj E, Jirstrom K, Gallagher WM, Brennan DJ, McNeish IA, Balkwill FR. Interleukin-6 as a therapeutic target in human ovarian cancer. Clin Cancer Res. 2011; 17:6083–6096.

10. Coleman RL, Duska LR, Ramirez PT, Heymach JV, Kamat AA, Modesitt SC, Schmeler KM, Iyer RB, Garcia ME, Miller DL, Jackson EF, Ng CS, Kundra V, Jaffe R, Sood AK. Phase 1-2 study of docetaxel plus aflibercept in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer. Lancet Oncol. 2011; 12:1109–1117.

11. Gotlieb WH, Amant F, Advani S, Goswami C, Hirte H, Provencher D, Somani N, Yamada SD, Tamby JF, Vergote I. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Oncol. 2012; 13:154–162.

12. Coxon A, Bready J, Min H, Kaufman S, Leal J, Yu D, Lee TA, Sun JR, Estrada J, Bolon B, McCabe J, Wang L, Rex K, Caenepeel S, Hughes P, Cordover D, Kim H, Han SJ, Michaels ML, Hsu E, Shimamoto G, Cattley R, Hurh E, Nguyen L, Wang SX, Ndifor A, Hayward IJ, Falcon BL, McDonald DM, Li L, Boone T, Kendall R, Radinsky R, Oliner JD. Context-dependent role of angiopoietin-1 inhibition in the suppression of angiogenesis and tumor growth: implications for AMG 386, an angiopoietin-1/2-neutralizing peptibody. Mol Cancer Ther. 2010; 9:2641–2651.

13. Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhomme C, Richardson G, Rincon DG, Coleman RL, Herzog TJ, Marth C, Brize A, Fabbro M, Redondo A, Bamias A, Tassoudji M, Navale L, Warner DJ, Oza AM. Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014; 15:799–808.

14. Secord AA, Blessing JA, Armstrong DK, Rodgers WH, Miner Z, Barnes MN, Lewandowski G, Mannel RS. Gynecologic Oncology Group. Phase II trial of cetuximab and carboplatin in relapsed platinum-sensitive ovarian cancer and evaluation of epidermal growth factor receptor expression: a Gynecologic Oncology Group study. Gynecol Oncol. 2008; 108:493–499.

15. Schilder RJ, Sill MW, Chen X, Darcy KM, Decesare SL, Lewandowski G, Lee RB, Arciero CA, Wu H, Godwin AK. Phase II study of gefitinib in patients with relapsed or persistent ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor mutations and immunohistochemical expression: a Gynecologic Oncology Group Study. Clin Cancer Res. 2005; 11:5539–5548.

16. Vergote IB, Jimeno A, Joly F, Katsaros D, Coens C, Despierre E, Marth C, Hall M, Steer CB, Colombo N, Lesoin A, Casado A, Reinthaller A, Green J, Buck M, Ray-Coquard I, Ferrero A, Favier L, Reed NS, Cure H, Pujade-Lauraine E. Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group, and Gynecologic Cancer Intergroup study. J Clin Oncol. 2014; 32:320–326.

17. Bookman MA, Darcy KM, Clarke-Pearson D, Boothby RA, Horowitz IR. Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group. J Clin Oncol. 2003; 21:283–290.

18. Farley J, Fuchiuji S, Darcy KM, Tian C, Hoskins WJ, McGuire WP, Hanjani P, Warshal D, Greer BE, Belinson J, Birrer MJ. Associations between ERBB2 amplification and progression-free survival and overall survival in advanced stage, suboptimally-resected epithelial ovarian cancers: a Gynecologic Oncology Group Study. Gynecol Oncol. 2009; 113:341–347.

19. Davies S, Holmes A, Lomo L, Steinkamp MP, Kang H, Muller CY, Wilson BS. High incidence of ErbB3, ErbB4, and MET expression in ovarian cancer. Int J Gynecol Pathol. 2014; 33:402–410.

20. Tanner B, Hasenclever D, Stern K, Schormann W, Bezler M, Hermes M, Brulport M, Bauer A, Schiffer IB, Gebhard S, Schmidt M, Steiner E, Sehouli J, Edelmann J, Lauter J, Lessig R, Krishnamurthi K, Ullrich A, Hengstler JG. ErbB-3 predicts survival in ovarian cancer. J Clin Oncol. 2006; 24:4317–4323.

21. Schoeberl B, Faber AC, Li D, Liang MC, Crosby K, Onsum M, Burenkova O, Pace E, Walton Z, Nie L, Fulgham A, Song Y, Nielsen UB, Engelman JA, Wong KK. An ErbB3 antibody, MM-121, is active in cancers with ligand-dependent activation. Cancer Res. 2010; 70:2485–2494.