Hudson Institute researcher’s findings may improve cancer drug clinical trial success rates

A researcher from Hudson Institute of Medical Research in Melbourne has discovered a class of biomarkers which may be used to predict which cancer patients will respond to a new class of cancer drugs.

Associate Professor Ron Firestein outlining BET inhibitor therapy
Associate Professor Ron Firestein

Associate Professor Ron Firestein, in a study, published on January 11 in the Journal of Clinical Investigation, has identified a genetic marker that predicts which cancers respond to a new form of epigenetic therapy called BET inhibitor therapy.

“Our paper shows that one consequence of BET activation in cancer is the expression of distinct long non-coding RNAs (lncRNAs),” Associate Professor Firestein said.

“These lncRNAs are excellent markers of where BET proteins are binding in the cancer genome and have significant potential to direct our clinical use of BET inhibitors.

“Indeed, we found that cancer cells which had high expression of these lncRNAs responded best to the BET inhibitor therapy.”

Unlike chemotherapy which indiscriminately attacks rapidly dividing cells, BET inhibitor drugs work on a genetic level. They bind to bromodomain extra-terminal (BET) proteins (which cancer cells use to maintain high oncogene expression) and ‘turn off’ the proliferation of cancer cells.

A growing number of clinical trials involving BET inhibitors are underway around the world, including in blood cancers like diffuse large B-cell lymphoma, multiple myeloma and acute myeloid leukaemia.

The head of Hudson’s Centre for Cancer Research, and formerly of Genentech in the US, A/Prof Firestein says the next step is a clinical trial to test the findings in patients.

“The next step for our work is to have a clinical trial where we test to see whether patients with this particular biomarker are responsive to the BET inhibitor,” A/Prof Firestein said.

“We would then look to develop a companion test that would show if a patient is a candidate for BET inhibitor therapy, or if they would respond better to a different form of treatment.

“Placing a cancer patient on drugs they won’t respond to wastes precious time and leads to undue suffering. The more we can identify and make use of these types of biomarkers, the better we will be at personalising cancer treatment and making sure patients are receiving appropriate care,” he said.

A/Prof Firestein says ensuring the effectiveness of targeted cancer therapies like BET inhibitor therapy will help to improve survival rates.

“We’ve been using chemotherapy agents for over fifty years. While it has shown success in different tumour types, patients invariably develop resistance to chemotherapy and it’s limited by toxicity issues,” A/Prof Firestein said.

Many BET inhibitor trial participants have exhausted other forms of treatment, including chemotherapy.

“I am hopeful that, together with clinical and Industry partners, we can quickly translate our findings into clinical trials that will test how well this biomarker strategy works to identify patients who will benefit most from BET inhibitors,” A/Prof Firestein said.

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