Improvement of ovarian cancer models to support preclinical development of new therapies for ovarian cancer

Lead researcher

A/Prof Clare Scott

A/Prof Clare Scott

Institution

The Walter and Eliza Hall Institute of Medical Research

Tumour type:

Ovarian

Years funded

2012-2016

Project description

Our project aimed to predict which treatment approaches will more successfully match individual cancers by better understanding the gene 'wiring' or control of these cancers.

We have developed new laboratory cancer 'models' or simulations in order to design treatment approaches better matched to specific ovarian cancer subtypes. These laboratory models allow us to fast-track analysis of the cancer with greater precision than studying cancer purely in a test tube. We have studied a number of different subsets of the most common aggressive type of ovarian cancer, high-greade serious ovarian cancer.

For example, ovarian cancers "wired" to be like those associated with the familial genes, BRCA1 and BRCA2, do not repair their DNA properly and can be treated by the new PARP inhibitor drug. However, PARP inhibitors do not work for all of these patients and we have identified a number of causes of resistance or treatment failure. As a result of these and similar findings in our models, three clinical trials are in development based on our work. 

What is the need? 

Survival rates for most rare cancers have not improved as they have done for more common cancers. More Australians diagnosed with certain sub-types of ovarian cancer and other rare cancers will die from their disease, than will those diagnosed with a more common cancer type.

Our hope is that future clinical trials will be designed to better match the individuals taking part and their cancers, resulting in a higher chance of success. As a result of our work in matching treatments to sub-types of ovarian cancer, we are now poised to extend this approach to other rare cancer types. 

What impact will this research have?

Controlling cancer well enough to allow individuals to get on with their lives is a reality for only some people with certain cancer types. Recently, new targeted cancer drugs properly matched to the cancer type have dramatically improved the chance of prolonged remission from the cancer. This is usually because the drug is matched to a particular controlling gene or growth pathway which has been high-jacked by the cancer.

The PARP inhibitor, olaparib or Lynparza was listed on the Australian 1 February 2017, for women with ovarian cancer who have inherited a gene change in either the BRCA1 or BRCA2 genes. This is the first treatment targeted to a gene in ovarian cancer to be listed on the PBS. The Dunlop Fellowship allowed me the time to play a major role in that submission to the PBS.

Our work has helped identify controlling genes or growth pathways which can indicate likely response to a drug - and also predict that a drug might not work. This has allowed us to design trials to get around drug resistance. In addition, our work will increase the chance that Australians with a rare cancer can also benefit from these advances in cancer control. 

 

"This is the first treatment targeted to a gene in ovarian cancer to be listed on the PBS. The Dunlop Fellowship allowed me the time to play a major role in that submission to the PBS."

Collaborators

The Dunlop Fellowship