Ovarian cancer in 2010 - are we making progress at last?
Stan Kaye
The Institute of Cancer Research and Royal Marsden Hospital, Sutton, UK
Thirty five years have elapsed since the first indications that cisplatin would play a major role in the treatment of ovarian cancer. Since then progress in therapy has been slow, relating as much to improvements in the delivery of multidisciplinary care as to developments in chemotherapy. The two major steps in that context were the replacement of cisplatin by the less toxic carboplatin, and the introduction of paclitaxel; most recently the use of this drug on a weekly rather than 3 weekly schedule is a further positive development.
But the major twin obstacles in chemotherapy – non-selectivity and drug resistance – have remained. In this context, progress in ‘targeted’ therapy, aimed at specific targets in ovarian cancer cells or in surrounding stroma, is welcome and long overdue. Specific examples showing exceptional promise include the use of anti-angiogenic agents, both antibodies and small molecules, particularly as a form of maintenance therapy. Other rational targets include the PI3K/AKT pathway and the alpha-folate receptor, and with these in mind trials are now under way with new drugs, both as single agents and in combination with chemotherapy aimed at reversing drug resistance. A further example of great interest is the concept of tumour synthetic lethality, whereby ovarian cancer cells which are unable to repair certain types of DNA damage, e.g. BRCA mutated cells, are particularly sensitive to PARP (poly ADP ribose polymerase) inhibitors. Clinical experience with these drug is very promising, and there are good reasons for expecting efficacy for this approach in a broad population of ovarian cancer patients. The development of laboratory assays, aimed at identifying biomarkers which will be predictive of those patients most likely to benefit, will be an important element in all these endeavours.
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