Scientists find small molecule that helps BRCA gene resist cancer treatment

6 Jul

In a new study they report in the journal Molecular Cell, scientists describe

how they identified a small molecule that helps the BRCA2 gene do its job. BRCA2 is a tumor

suppressor gene that in some mutated forms can cause breast and ovarian cancer in as many as

60% of women.

magnifying glass examines portion of DNA
The researchers say understanding how cancer cells repair DNA breaks will help develop new ways to counter resistance to chemotherapy.

Like normal cells, cancer cells need to repair DNA to survive. This is somewhat of a

paradox – in their case, they are concerned with maintaining the integrity of “faulty”


DNA repair in cells – both healthy and cancerous – is controlled by genes, including BRCA


Decades ago, scientists discovered that variants of BRCA1 and BRCA2 genes are markers for increased

risk of breast cancer.

According to the National Cancer Institute, together, BRCA1 and BRCA2 mutations account for about 20-25% of hereditary breast cancers and about 5-10% all breast cancers. In addition, mutations in these genes account for around 15% of all ovarian cancers.

Breast and ovarian cancers involving BRCA1 and BRCA2 mutations tend to develop earlier in life than their non-hereditary counterparts.

BRCA mutations are also known to play a role in ovarian, prostate and

pancreatic cancers.

While chemotherapy drugs can be effective for fighting cancer in people with BRCA

mutations, there is a tendency for the cancer to develop resistance to the drugs. The BRCA

proteins develop secondary mutations that continue to promote cancer growth.

Findings point to a way to counter drug resistance in BRCA cancers

Now, scientists at Yale School of Medicine in New Haven, CT, have pinpointed a key molecule

called co-factor DSS1 that helps the BRCA2 gene to repair DNA.

They note how “DSS1 acts as a DNA mimic,” and without it, BRCA2 mutations cannot do their job

of repairing DNA – which is key to the survival of cancer cells.

The team says the findings point to a possible way to decrease drug resistance in cancers

involving BRCA genes.

Senior author Patrick Sung, a professor of molecular biophysics and biochemistry, suggests

drugs that interfere with DSS1 function could be developed and used with existing drugs to

overcome this resistance, and explains:

“We can design specific targets for drug development only if we fully understand

the key players and how they work in the pathway for repairing DNA breaks.”

Grants from the National Institutes of Health helped fund the study.

Meanwhile, Medical News Today recently learned about new research that suggests daily aspirin may prevent breast cancer development and

recurrence. Researchers writing in the journal Laboratory Investigation describe how

daily low-dose aspirin almost halved tumor growth in mice with breast cancer.

Written by Catharine Paddock PhD