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Resistance to chemotherapy and role of BRCA2 February 22, 2008

Posted by ramunas in BRCA, cancer genetics, hereditary cancer, ovarian cancer, research.
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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 like cisplatin. Unfortunately, many BRCA2 tumours develop resistance to cisplatin (ref.).

(BRCA2 repairs a stretch of DNA; source)

Interestingly, the researchers found that, when exposed to cisplatin, some ovarian cancer cells develop secondary mutations on their BRCA2 gene that restore the 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 finds the similar mechanism involved in resistance to PARP (Poly(ADP-Ribose) polymerase) inhibitors, a new class of drugs which are known to 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 by Nature.

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Comments»

1. Steve Murphy MD - February 22, 2008

Great Post.
I look forward to the positive mutation assays. Boy what a legal/patent nightmare!
-Steve

2. joe simms - April 5, 2008

Finding original ideas for overcoming the various mechanisms of resistance in cancers is the main reason for my blog. Even after 20 years , we still seem to be frustated by the complexity of an effective treatment for this aspect of cancer . Take a look at the Resistance map I am building at my site.

3. David Halls - June 17, 2008

Hi-

“The discovery raises the possibility that blocking BRCA2 function in such patients might allow doctors to overcome drug resistance and continue with cisplatin treatment.”

Do you know if any research is being carried out in this area now?

Many thanks

David

4. How Long before your Laptop finds a cure for Cancer? - September 13, 2011

[…] changes. The reason chemotherapy consists of a cocktail of drugs rather than one, is to tackle the resistance to treatment that cancer cells can develop making one drug on its own, […]


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