Send to

Choose Destination
Cancer Biol Ther. 2008 Jul;7(7):1004-5.

Secondary BRCA1 and BRCA2 alterations and acquired chemoresistance.

Author information

Medical Oncology Branch, National Cancer Institute; Bethesda, Maryland 20892, USA.


Tumor suppressor BRCA1 and BRCA2 are frequently mutated in familial breast and ovarian cancer. More than ten percent of women with breast or ovarian cancer carry BRCA1 or BRCA2 (BRCA1/2) mutations. Cancers that arise in mutation carriers have often lost the wild-type allele through somatic alterations during tumor progression. BRCA1/2 play important roles in homologous recombination repair of DNA double-strand breaks. Because of this, BRCA1/2-deficient cancers often have a better response to DNA cross-linking agents such as platinum analogues and to poly(ADP-ribose) polymerase (PARP) inhibitors. However, over time, the majority of these BRCA1/2-deficient cancers become resistant and patients die from refractory diseases. Three recent studies demonstrated that acquired resistance to platinum analogues or PARP inhibitors in tumors carrying frame-shift BRCA1/2 mutations came from restored BRCA1/2 expression and HR function due to secondary intragenic mutations that corrected the open reading frames of mutated BRCA1/2.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Taylor & Francis Icon for PubMed Central
Loading ...
Support Center