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Resistance to chemotherapy and role of BRCA2

Posted Jun 24 2008 11:08am

Tumor resistance to chemotherapy is an often failure of successive treatment (together with adverse effects).

As you know, BRCA2 mutations are associated with an increase in breast and ovarian cancer risk, as the gene’s normal function is to repair damaged DNA. But these cancer-causing faults are bad news for the tumour itself, as they also render it sensitive to DNA-damaging chemotherapy drugs likecisplatin. Unfortunately, many BRCA2 tumours develop resistance to cisplatin (ref.).

(BRCA2 repairs a stretch of DNA;source)

Interestingly,the researchers foundthat, when exposed to cisplatin, some ovarian cancer cells develop secondary mutations on their BRCA2 gene thatrestorethe gene’s ability to repair DNA (via). This is called positive mutation in general genetics - a mutation which improves adaptive properties of a cell (if we look from a cancer cell perspective).

The discovery raises the possibility that blocking BRCA2 function in such patients might allow doctors to overcome drug resistance and continue with cisplatin treatment. And maybe this mechanism will be true to other DNA-repair genes such as BRCA1, which may help explain drug resistance to a variety of cancers (via).

Another study findsthe similar mechanism involved in resistance toPARP (Poly(ADP-Ribose) polymerase)inhibitors, a new class of drugs whichare knownto be more effective in BRCA1/2 mutation cases, because they work by selectively killing cells which have no functioning BRCA gene.

These observations have implications for understanding drug resistance in BRCA mutation carriers as well as in defining functionally important domains within BRCA2 (ref.). Sure, therefore it is featured byNature.

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