Fast-Tracking Pro-Survival Proteins from the Lab to the Clinic

• Project description: Professor Geoff Lindeman will undertake two clinical trials to test the safety and effectiveness of a new class of drugs, BH3 mimetics, in patients with advanced breast cancer.
• Why this work is needed: Currently, metastatic breast cancer has a much lower survival rate than breast cancer in general. The study will determine whether BH3 mimetics may be used to treat metastatic breast cancer to improve the outcomes of those diagnosed.
• Expected outcomes: If successful, the project findings could help fast-track a new class of drugs into the clinic for people affected by breast cancer. It is hoped that these drugs will ultimately provide more durable treatment responses for patients with advanced breast cancer.

Project details
Certain blood cancers are sustained by high levels of a ‘survival’ protein called BCL-2, which makes them more resistant to therapy. A new class of drug, BH3 mimetics, is showing tremendous promise in the treatment of these blood cancers. These drugs block the BCL-2 protein, removing its protective effect and leading to death of the cancer cells.

Most breast cancers also contain high levels of the BCL-2 survival protein (and a related survival protein, MCL-1), suggesting that the BH3 mimetic drugs may also be a potential treatment option for solid tumours. One of the most well-known BH3 mimetic drug is called venetoclax, which is used for blood cancers such as leukemia and lymphoma. However, it has not been used in breast cancer to date.

In this new NBCF-funded study, clinician-scientist Professor Geoff Lindeman will explore the use of BH3 mimetics in translation studies from the lab to the clinic. Prof Lindeman and his team will firstly test venetoclax in preclinical models of a number of different breast cancer subtypes. They will also undertake two clinical trials to directly test the safety and effectiveness of venetoclax in patients with advanced (metastatic) breast cancer.

The project will fast-track this new drug to the clinic, providing patients with access to this treatment option in an earlier timeframe. It is hoped that the drug class will provide deeper and more durable treatment responses and improve health outcomes.