VCA grant brings personalised cancer therapy one step closer

Dr Arun Azad

A world-first clinical trial at Monash Health Translation Precinct, funded by a Victorian Cancer Agency (VCA) grant, will determine if a new class of drug is effective in prostate and colorectal cancer patients.

Prostate and colorectal cancers are two of the most commonly diagnosed cancers in Australia.  More than 3000 men die of prostate cancer and over 4100 lives are claimed by colorectal cancer every year in Australia.

Researchers at Monash University and the Hudson Institute of Medical Research have received a highly competitive VCA grant worth $2 million to determine whether particular prostate and colorectal cancer patients will respond to a new class of cancer drug known as BET inhibitors.

“BET inhibitors are a new type of therapy that can slow down the growth of cancers by switching off cancer genes,” said lead researcher Dr Arun Azad, Senior Research Fellow at Monash University and Consultant Medical Oncologist at Monash Health. 

Unlike chemotherapy which indiscriminately attacks ‘good’ and ‘bad’ cells, BET inhibitors—a type of epigenetic therapy—work on a genetic level to turn off the growth of cancer cells.

“We believe that patients who have a particular biomarker known as long non-coding RNAs may respond best to BET inhibitor therapy.”

“Importantly, we can easily identify which patients have these long non-coding RNA biomarkers through examining their tissue sample,” added Dr Azad.

Dr Azad believes around 50% of prostate and colorectal cancer patients have the RNA biomarker and predicts these patients will respond well to the new class of drug.

“While there are other trials investigating BET inhibitors, our clinical trial is the first in the world to look at the association between patients with RNA molecules and BET inhibitors.”

“We’re ultimately hoping to increase the range of therapeutic options available to prostate and colorectal cancer patients,” added Dr Azad.  “This is all about personalised medicine; we want to be able to use the right drug for the right patient.”

The collaborative research project builds on the previous work of Hudson Institute’s Associate Professor Ron Firestein, who identified the RNA biomarker and potential benefit of BET inhibitors in pre-clinical models in his previous laboratory at Genentech Inc.

 “Ensuring the effectiveness of targeted cancer therapies not only improves survival rates but provides another option to patients who invariably develop resistance to chemotherapy,” said Associate Professor Firestein who is also co-lead investigator on the study.

Undertaken at Monash Health, the trial will recruit twenty five patients with advanced prostate or colorectal cancer and for whom other treatments options have failed. 

Dr Azad said that while there is a range of drugs that work well in prostate and colorectal cancer, patients eventually become resistant so more options are needed.

“We need to use these treatment options the smartest way we can and not use the scattergun chemotherapy approach where we give all patients the same treatment, and if 20% respond, that’s great.”

“What about the other 80% of patients for whom chemo was never going to work, who suffered unnecessary toxicity, and wasted time, effort and a lot of money?”

Dr Azad and Associate Professor Firestein are very optimistic about the potential for epigenetic therapies like BET inhibitors.

“If we can define which patients will respond best to treatment, we’re genuinely personalising cancer care,” said Dr Azad. 

“Personalised cancer care is the Holy Grail—everyone wins but most importantly the patients.”

Co-collaborators on this study include Monash University’s Professor Gail Risbridger, Associate Professor Helen Abud, colorectal surgeon Associate Professor Paul McMurrick and Cabrini’s Dr Simon Wilkins.