Study Explains Why Some Cancers may Respond Poorly to Key Drugs Discovered

A driver of the drug resistance that can make a life or death difference for patients with BRCA1/2 mutations has been discovered by scientists at The University of Texas at Austin and Ajou University. "A major issue with cancer treatments is the development of resistance," said Kyle Miller, a UT Austin associate professor of molecular biosciences. "When treatments stop working for patients, it's incredibly demoralizing and it's been a huge drive in research to understand these resistance mechanisms."

PCAF protein helps doctors predict which patients will become resistant to a class of drugs frequently used to treat BRCA 1/2-deficient tumors. PCAF also may offer important clues about cell replication. The findings are published in the journal Molecular Cell.

The PCAF protein promotes DNA damage in BRCA 1/2-mutated cancer cells. Patients with reduced levels of this protein are likely to have poor outcomes and develop resistance to a type of drug that is used to treat BRCA-deficient tumors, called a PARP inhibitor.

"PARP inhibitors are an important breakthrough in treating these aggressive cancers," Miller said. "What we found is that when levels of PCAF are low, it actually protects the cancer cells from this drug. By testing biopsy samples, doctors may be able to tell using PCAF as a molecular marker for PARP inhibitor responses what treatment may work best for a patient."

"The focus in my lab is on understanding chromatin and its impact on replicating DNA, protecting DNA and controlling access to DNA," Miller said. "Our goal is to understand how every molecule is interacting inside our cells, as this gives clues to what is going wrong in human diseases."

Source-Medindia