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Researchers identify biological indicator of response to new ovarian cancer drug

Researchers have found a way of identifying which patients are likely to respond well to a new anti-cancer drug called rucaparib.

Results of clinical trials have shown that women with tumours that are sensitive to platinum-based chemotherapy and who carry inherited mutations in the BRCA1/2 genes respond well to rucaparib. But in new findings presented at the 26th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, researchers say that they have identified a biological indicator (biomarker) that can predict which women without BRCA1/2 mutations will respond to the drug as well.

Rucaparib is designed to inhibit a protein called poly (ADP-ribose) polymerase (), which is involved in repairing damaged DNA. Inhibiting can prevent from repairing themselves and so they die. Women with BRCA1/2 mutations who have developed ovarian cancer respond well to rucaparib because the genetic mutation has already affected one method of repairing damaged DNA in cells, and the PARP inhibitor attacks the ’ only other DNA repair mechanism.

However, Professor Elizabeth Swisher, from the University of Washington School of Medicine (Seattle, USA), will tell the Symposium that, in addition to identifying BRCA1/2 mutations, there are other indicators of defective DNA repair that could be used to predict responsiveness to PARP inhibitors. She and her colleagues from research centres in the North America, Europe, and Australia have seen good responses to rucaparib in women with ovarian cancers exhibiting a form of cell damage called genomic loss of heterozygosity (LOH), in which an entire chromosomal region on one copy of the genome is lost.

In the ARIEL2 phase 2 clinical trial of rucaparib, which started in October 2013, preliminary data from 121 patients have shown responses to the drug in women with tumours that have high genomic LOH, as well as in patients with BRCA1/2 mutations. [2]

“This is the first time that we have predictors to identify women with ovarian cancer other than those with a known BRCA1 or BRCA2 mutation who are likely to respond to a PARP inhibitor. This will allow more focused application of PARP inhibitors to the women most likely to benefit from treatment with a PARP inhibitor. The more we can identify responders to specific therapies, the better women and their doctors can select the most effective treatments option,” Prof Swisher will say.

Women with platinum-sensitive ovarian cancer can be treated with platinum-based chemotherapies, which can be repeated if the cancer should recur. However, the toxicity of the chemotherapy results in serious, adverse side-effects and, furthermore, it has to be given intravenously. Rucaparib is taken in pill form and is less toxic.