Role of Molecular Agents and Targeted Therapy in Clinical Trials for Women With Ovarian Cancer

There is now a greater understanding of the molecular pathways in ovarian cancer, and using this knowledge, a large number of new therapeutic agents can be tested. The success of these drugs will depend on selecting drugs that target known key dysfunctional molecular pathways. To make best use of these compounds, prognostic and predictive biomarkers need to be identified. Novel methods of assessment such as functional imaging need to be developed as additional biological end points to evaluate these therapies. Promising antitumor activity has been observed with some drugs, and careful consideration is needed to determine in what circumstances new agents, such as antiangiogenic compounds, could be considered as a standard therapy. These areas were discussed at the 4th Ovarian Cancer Consensus Conference.

[1]  Kylie L. Gorringe,et al.  Amplicon-Dependent CCNE1 Expression Is Critical for Clonogenic Survival after Cisplatin Treatment and Is Correlated with 20q11 Gain in Ovarian Cancer , 2010, PloS one.

[2]  B. Karlan,et al.  Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  A. Tutt,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 , 2010, The Lancet.

[4]  B. Monk,et al.  Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  A. Oza,et al.  Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer. , 2010 .

[6]  E. Berns,et al.  Pathway analysis of gene lists associated with platinum-based chemotherapy resistance in ovarian cancer: the big picture. , 2010, Gynecologic oncology.

[7]  Carlos Caldas,et al.  Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary , 2010, The Journal of pathology.

[8]  A. Reuss,et al.  Prognostic Relevance of Uncommon Ovarian Histology in Women With Stage III/IV Epithelial Ovarian Cancer , 2010, International Journal of Gynecologic Cancer.

[9]  E. Berns,et al.  Integrated genomics of chemotherapy resistant ovarian cancer: a role for extracellular matrix, TGFbeta and regulating microRNAs. , 2010, The international journal of biochemistry & cell biology.

[10]  R. Messmann,et al.  PRECEDENT: A randomized phase II trial comparing EC145 and pegylated liposomal doxorubicin (PLD) in combination, versus PLD alone, in subjects with platinum-resistant ovarian cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  A. Ashworth,et al.  Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. , 2009, The New England journal of medicine.

[12]  A. Glas,et al.  Gene expression profiling: decoding breast cancer. , 2009, Surgical oncology.

[13]  Varda Rotter,et al.  When mutants gain new powers: news from the mutant p53 field , 2009, Nature Reviews Cancer.

[14]  L. Old,et al.  8000 Efficacy and safety of farletuzumab, a humanized monoclonal antibody to folate receptor alpha, in platinum-sensitive relapsed ovarian cancer subjects: preliminary data from a phase-2 study , 2009 .

[15]  A. Sood,et al.  Aflibercept in epithelial ovarian carcinoma. , 2009, Future oncology.

[16]  E. D. de Vries,et al.  Modest effect of p53, EGFR and HER-2/neu on prognosis in epithelial ovarian cancer: a meta-analysis , 2009, British Journal of Cancer.

[17]  G. Jayson,et al.  A randomized phase II placebo-controlled trial using maintenance therapy to evaluate the vascular targeting agent BIBF 1120 following treatment of relapsed ovarian cancer (OC). , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  D. Alberts,et al.  Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a Phase III Trial of the Gynecologic Cancer Intergroup. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  Joshy George,et al.  Integrated Genome-Wide DNA Copy Number and Expression Analysis Identifies Distinct Mechanisms of Primary Chemoresistance in Ovarian Carcinomas , 2009, Clinical Cancer Research.

[20]  S. Leung,et al.  Ovarian Carcinoma Subtypes Are Different Diseases: Implications for Biomarker Studies , 2008, PLoS medicine.

[21]  A. du Bois,et al.  [Central pathology review. Inclusion criterion for clinical studies of ovarian carcinomas?]. , 2008, Der Pathologe.

[22]  S. Cannistra,et al.  Gene-expression profiling in epithelial ovarian cancer , 2008, Nature Clinical Practice Oncology.

[23]  M. Markman Mandating prospectively defined endpoints for ovarian cancer phase 2 trials: a strategy to improve the quality of gynecologic cancer clinical research. , 2008, Gynecologic oncology.

[24]  A. Al-Attar,et al.  Vascular Endothelial Growth Factor Expression in Ovarian Cancer: A Model for Targeted Use of Novel Therapies? , 2008, Clinical Cancer Research.

[25]  P. Low,et al.  Folate receptor alpha as a tumor target in epithelial ovarian cancer. , 2008, Gynecologic oncology.

[26]  S. Groshen,et al.  Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  P. Spellman,et al.  Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities , 2008, BMC Cancer.

[28]  Michael W Sill,et al.  Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  Howard Mackey,et al.  Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  John P A Ioannidis,et al.  Almost all articles on cancer prognostic markers report statistically significant results. , 2007, European journal of cancer.

[31]  R. Ozols,et al.  Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  G. Amann,et al.  Analysis of gene amplification and prognostic markers in ovarian cancer using comparative genomic hybridization for microarrays and immunohistochemical analysis for tissue microarrays. , 2006, American journal of clinical pathology.

[33]  D. Tong,et al.  Clinical Relevance of Dominant-Negative p73 Isoforms for Responsiveness to Chemotherapy and Survival in Ovarian Cancer: Evidence for a Crucial p53-p73 Cross-talk In vivo , 2005, Clinical Cancer Research.

[34]  J. Boyd,et al.  Gene Expression Profiles of Serous, Endometrioid, and Clear Cell Subtypes of Ovarian and Endometrial Cancer , 2005, Clinical Cancer Research.

[35]  Alan Ashworth,et al.  Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy , 2005, Nature.

[36]  Wolfgang A Weber,et al.  Monitoring response to treatment in patients utilizing PET. , 2005, Radiologic clinics of North America.

[37]  G. Yancopoulos,et al.  Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[38]  C. Marth,et al.  Why did p53 gene therapy fail in ovarian cancer? , 2003, The Lancet. Oncology.

[39]  L. Morrison,et al.  Cyclin E expression is a significant predictor of survival in advanced, suboptimally debulked ovarian epithelial cancers: a Gynecologic Oncology Group study. , 2003, Cancer research.

[40]  E. Eisenhauer,et al.  Novel endpoints and design of early clinical trials. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[41]  H. Caffier,et al.  Prognostic relevance of serum vascular endothelial growth factor in ovarian cancer. , 2000, Anticancer research.

[42]  N. Ferrara,et al.  Role of vascular endothelial growth factor in ovarian cancer: inhibition of ascites formation by immunoneutralization. , 1998, The American journal of pathology.

[43]  D. Cruickshank,et al.  The prognostic value of serum CA 125 in patients with advanced ovarian carcinoma: an analysis of 573 patients by the Medical Research Council Working Party on Gynaecological Cancer , 1992, International Journal of Gynecologic Cancer.