Creating New Treatments for Metastatic Breast Cancer

• Project description: Dr Liz Caldon and her team have created experimental models that mimic resistance to CDK4/6 inhibitors, a new class of drugs now in clinical use. She will use these models to better understand how resistance develops. From this, they will determine whether existing drugs can be used to treat CDK4/6 resistant cancer or whether better alternatives can be identified.
• Why this work is needed: CD4/K inhibitors may be used to treat advanced ER+ breast cancer. However, there are currently no strategies to treat women whose breast cancer has become resistant to CDK4/6 inhibitors. This research will help develop new ways to prolong the lives of those with advanced ER+ breast cancer.
• Expected outcomes: If successful, these findings can be translated into an early phase clinical trial for patients with drug-resistant ER+ breast cancer.

Project details
Advanced estrogen receptor positive (ER+) breast cancer is responsible for over half of breast cancer deaths. CDK4/6 inhibitor drugs such as Palbociclib and Ribociclib were approved for advanced ER+ breast cancer in 2015 in the USA.  These are the most effective drugs to be released for ER+ breast cancer in the last 10 years, doubling progression-free survival rates. In addition, the drugs have the advantage of being orally administered with few side effects.

Despite the success, drug resistance to CDK4/6 inhibitors is already being observed in the clinic, with the cancer often returning after about 20 months of treatment. Given these drugs are still so new, there is no knowledge or strategy on how to treat patients once their cancer becomes resistant to CDK4/6 inhibitors.

NBCF-funded researcher Dr Liz Caldon and her team have developed experimental models that mimic the development of CDK4/6 resistance and will now study the mechanisms of resistance in more detail. They will determine whether existing drug treatments could be used to treat CDK4/6 resistant cancer, or whether better alternatives can be identified. These findings will be developed into early phase clinical trial of treatment options for patients with drug-resistant ER+ breast cancer.