BRCA mutations in breast cancer

Genetic testing for BRCA1 and BRCA2 mutations can provide important information for women who are concerned about their breast and ovarian cancer risks and need to make relevant prevention and medical management decisions.

To date, lifetime risks of breast cancer in individual BRCA1/2 mutation carriers have been challenging to apply in clinical decision making. Published risk estimates vary significantly and are very dependent on the characteristics of the population under study. You can read more about in this article (free PDF download).

Another study interpreted validated functional data from the transactivation activity of BRCA1 in combination with analysis of protein modelling based on the structure of BRCA1 BRCT domains. With additional clinical and structural evidence, they were able to classify all missense variants in the BRCA1 COOH-terminal region. These results brought functional assays for BRCA1 closer to clinical applicability.

Cancer risks in a population-based study of BRCA1/2 mutation carriers have been recently estimated, but the numbers are still in their infancy and may be influenced by different risk factors. It is likely that there is broad variation in breast cancer risk among carriers of BRCA1 and BRCA2 mutations and ethnicity may also confer differences in risks associated with BRCA mutations.

What's stopping EGFR inhibitors from being more effective?

Response rates with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in cancer treatment have been low. However, a recent study may have shed some light by revealing a kinase-independent function of EGFR in maintaining cell survival.

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Using prostate, breast and colon cancer cells, it was demonstrated that small interfering RNA (siRNA)-mediated knockdown of EGFR, but not inhibition of EGFR kinase activity, leads to autophagic cell death. Autophagy can occur when external energy sources are low or unobtainable and, although glucose levels remained constant in cells treated with kinase inhibitors, they were decreased by around 50% in cells transfected with EGFR siRNA.

The study found that EGFR–SGLT1 may confer a survival advantage to cancer cells by maintaining a basal level of intracellular glucose and preventing autophagy. This may help to explain previous data indicating that inhibition of EGFR kinase activity is not sufficient to induce cell death, or to negate all of the functions of EGFR.

Targeting both kinase-dependent and kinase-independent functions of EGFR may be necessary for more successful therapy in the future.

Source:

Cancer Cell (free download)