PARP inhibitors effective against cancer cells with fault CBLC gene, says ICR

Researchers at London’s Institute of Cancer Research (ICR) have found that cancer cells with a fault in the protein-coding CBLC gene could be sensitive to the poly ADP-ribose polymerase (PARP) inhibitor drugs.

Approved in December last year to treat ovarian cancer patients with BRCA1 or BRCA2 mutations, PARP inhibitor Olaparib is the first cancer drug directed at an inherited genetic fault.

The Institute of Cancer Research team leader and study co-leader Dr Chris Lord said: “Our study has found that defects in a rather poorly studied DNA repair gene called CBLC seem to greatly increase sensitivity to olaparib, a PARP inhibitor, which is currently licensed only for BRCA-mutated cancer.

“PARP inhibitors are an exciting new class of cancer drug. Understanding why different types of tumour cells respond to PARP inhibitors will play a critical part in making sure these new drugs are used in the most effective way.”
“Understanding why different types of tumour cells respond to PARP inhibitors will play a critical part in making sure these new drugs are used in the most effective way.”

Funded by European Union (EU) in the UK, the study has been published in the journal Oncotarget and was conducted in collaboration with researchers in Denmark and the Czech Republic.

Using RNA interference screening that suppresses genes, researchers systematically examined genes, with 25,000 genes in the human genome affected the response of cancer cells to olaparib.

The ICR team observed that cancer cells with a defect in the CBLC gene were sensitive to the drug as those with a faulty BRCA2 gene.

Researchers noticed that CBLC normally allows cells to repair damaged DNA by fixing broken DNA strands back together, by analysing the molecular processes that the CBLC gene controls.

According to ICR, this finding demonstrated that a defect in DNA repair mechanisms explains the sensitivity of CBLC-defective cancer cells to PARP inhibitors, allowing researchers to know about the action of another DNA repair mechanism.