Understanding how cancer cells become resistant to a novel treatment of blood cancers

Lead researcher

Dr Gretchen Poortinga, Prof Grant McArthur, Prof Ross Hannan

Dr Gretchen Poortinga, Prof Grant McArthur, Prof Ross Hannan

Institution
Peter MacCallum Cancer Centre, The University of Melbourne

Tumour type:
Leukaemia, Lymphoma

Years funded
2016-2018

Project description

We have developed a novel drug targeting the hallmark of all cancers - uncontrolled cell growth. This exciting new cancer treatment, CX-5461, is now being tested in a clinical trial for patients with leukemia and lymphoma.

We already know from our preclinical research that cancer cells become resistant to CX-5461, so we have developed a unique method for isolating the resistant cells and identifying the gene mutations that lead to drug resistance.

We now aim to determine if these mutations also arise in the patients being treated with this drug in the clinical trial. 

What is the need? 

This research will identify pathways of drug resistance to CX-5461, which is critical if we are to maximise its benefit for patients. Our work should also lead to the development of new therapeutic strategies, in particular novel drug combinations with CX-5461.

What impact will this research have?

Our research will directly contribute to the treatment of cancer and have immediate impact on the development of the current clinical trials of CX-5461.

We aim to identify the mechanisms of resistance in a preclinical mouse model as a means of identifying why patients relapse. We will then translate these findings to patients in the ongoing trial by monitoring them for the biomarkers of drug resistance we have identified. This will immediately inform treatment decisions for individual patients. We hope that deeper understanding resistance- causing mechanisms will lead to the identification of new therapies for use in combination with CX-5461 to improve its overall effectiveness. 

 

Project timeline

20162017 2018 

                Initiate lymphoma transplants to build the bank of CX-5461 resistant tumours and initiate next generation sequencing (NGS) on clones.  

 

           Complete majority of NGS and genomic data analyses. Assess resistance-screen candidates and initiate their analysis.

 Ongoing data analysis of select screen candidates and screening human cell lines with panel of resistance-screen candidates.

 

"We have developed a novel drug targeting the hallmark of all cancers- uncontrolled cell growth. This exciting new cancer treatment, CX-5461, is now being tested in a clinical trial for patients with leukemia and lymphoma."