New Class of Breast Cancer Drugs May Be Effective in Larger Patient Group

Errors in genes may leave tumors susceptible to PARP inhibitors.

A pioneering class of breast cancer drugs that target mutations in the BRCA genes may also be effective treating tumors with a different type of genetic fault, a recent study found.

Published in the journal Oncotarget, researchers at The Institute of Cancer Research in the UK found errors in the CLBC gene leaves cancer cells vulnerable to PARP inhibitor drugs, with approximately 2% of all tumors carrying this type of defect.

"PARP inhibitors are an exciting new class of cancer drug. Understanding why different types of tumor cells respond to PARP inhibitors will play a critical part in making sure these new drugs are used in the most effective way,” study co-lead Chris Lord, MD, said in press release.

The PARP inhibitor olaparib was the first cancer drug to hit the market that targets an inherited genetic fault in ovarian cancer patients with BRCA1 or BRCA2 mutations.

Through a process called RNA interference screening, which analyzes gene function, the researchers evaluated which genes among 25,000 found in the human genome were able to affect the response of cancer cells to olaparib.

The researchers found cancer cells with the CBLC gene defect were just as sensitive to olaparib as cells with the defective BRCA2 gene. In an evaluation of the molecular processes controlled by the CBLC gene, the researchers noted that the gene typically permits cells to repair damaged DNA by fixing broken strands back together, which indicates a flaw in DNA repair mechanisms that causes the sensitivity of CBLC-defective cancer cells to PARP inhibitors.

This flaw also eliminates the action of another DNA repair mechanism.

DNA repair is frequently disrupted in cancer cells that sacrifice genetic stability when gaining mutations that allow the cells to uncontrollably split. The cancer cells may be particularly vulnerable to treatments that block DNA repair proteins, because they may lack an alternative repair system.

"This new study adds to evidence that PARP inhibitors can be effective in a broader group of patients than those with BRCA mutations, and could lead to them being used more widely in patients with other kinds of faults in DNA repair,” Paul Workman, chief executive of The Institute of Cancer Research, said in a press release.