Researchers at Peter Mac have discovered a genetic mutation which may lead to a new combination drug treatment to be tested in forthcoming clinical trials in Mantle Cell Lymphoma (MCL) patients.

The study, led by Peter Mac Professors Mark and Sarah-Jane Dawson, Dr Rishu Agarwal and Dr Yih-Chih Chan, looked at the 30 per cent of patients with MCL who fail to respond to existing therapies.

They found that this cohort of patients had mutations in a highly conserved protein complex that regulates gene expression and these mutations led to the increased expression of a key survival protein called BClxL which protected the cancer cells from the drug therapy. 

The research tested the cells of these patients against a series of drugs that could work with the existing treatment regime. 

“Once we found the genetic mutations associated with those MCL patients who are resistant to current drug therapy, it was possible to find drugs that counteracted these changes,” Professor Sarah-Jane Dawson said. 

A key element to this research has been the incorporation of a test called a liquid biopsy, which allows trace amounts of cancer DNA to be detected in a patient’s blood. 

The test, established by a team led by Professor Sarah-Jane Dawson, allows the genetic changes associated with resistance to the cancer drugs ibrutinib and venetoclax to be identified and monitored through regular blood tests, limiting the need for cancer patients to endure invasive biopsies to monitor their disease and response to treatment.

According to Professor Mark Dawson, it will now be possible to look for these “resistance conferring” gene mutations in newly diagnosed patients with MCL, to determine whether they will respond to current therapies or if they may need to enrol in a clinical trial for patients with a likelihood of resistance.

 “Working out why these patients fail to respond to treatment, and finding a potential new drug to overcome the resistance, will likely change clinical practice for patients with this disease,” Prof Dawson said.

Professor Sarah-Jane Dawson will present the data at the American Society for Haematology meeting in San Diego in early December. 

Patients will have the opportunity to enter a clinical trial for the new combination therapy in 2019.