Relevant molecular markers and targets.
Ovarian cancer is a heterogeneous disease with extensive cytogenetic and molecular heterogeneity including aneuploidy, chromosomal alterations, mutations and overexpression as well as a natural propensity to disseminate and spread, making it difficult to diagnose at an early stage. Insights into the molecular mechanisms operative in cancer development, progression and metastasis have uncovered a wide array of targets for therapeutic intervention. In the absence of a common driving oncogene in ovarian cancer, single targeted therapy for this disease is unlikely to yield significant clinical benefit. Tailored approaches that combine molecular targeting agents with cytotoxic regimens hold great promise when used in primary treatment, during consolidation and maintenance therapy, and in the treatment of persistent or recurrent disease. The most promising treatment strategies are those that target the drivers of tumorigenesis and enhance the activity of cytotoxic agents. Receptor tyrosine kinases, non-receptor tyrosine kinases, serine/threonine kinases, transferases, proteases and deacetylases are among the relevant molecular markers and targets for ovarian cancer that are discussed. Collaboration, coordination, creativity and aggressive outreach to patients and their advocates are essential for success in running the concurrent trials with multiple clinical end points and embedded translational research that are needed to evaluate the array of promising targeted therapeutics and combinations. Validated biomarkers, surrogate specimens and end points, and additional clinically relevant in vitro and in vivo models for ovarian cancer are needed to facilitate the drug development and evaluation process, and ultimately to make meaningful improvements in the diagnosis, prevention and management of ovarian cancer.
Darcy
Kathleen M
KM
Translational Research Scientist, Gynecologic Oncology Group, Statistical and Data Center, Roswell Park Cancer Institute, Research Studies Center, Rm. 516, Carlton and Elm Streets, Buffalo, NY 14263, USA. darcy@gogstats.org <darcy@gogstats.org>
Schilder
Russel J
RJ
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*
D014408:Biomarkers, Tumor