Titles and Affiliations

Joint Division Head, Stem Cells and Cancer
The Walter and Eliza Hall Institute of Medical Research
Victoria, Australia

Research area

Improving the effectiveness of therapies for women with estrogen receptor-positive breast cancer.

Impact

About one quarter of women with early-stage, estrogen receptor (ER)-positive breast cancer will later be diagnosed with metastatic breast cancer. A therapeutic regimen that includes endocrine therapy plus one of a class of drugs called CDK 4/6 inhibitors has dramatically extended the lives of patients with MBC, but the tumors ultimately develop resistance. Dr. Lindeman is testing the safety and effectiveness of a triple therapy that combines endocrine therapy and CDK4/6 inhibitor, a potent inhibitor of BCL2, a “survival” protein that helps keep cancer cells alive. His studies could enable new treatment options for women with ER-positive breast cancer that is no longer responding to the therapy.

Progress Thus Far

Dr. Lindeman’s team conducted laboratory studies of the combination of a BCL2 inhibitor with hormone therapy and a cell cycle (CDK4/6) inhibitor. They have confirmed that the efficacy of triple therapy is superior to dual therapy in ER-positive breast cancer models and have launched a phase I clinical trial to establish safety and dosing for the triple therapy.

What's next

In the upcoming year, Dr. Lindeman will continue his work exploring whether there is a role for adding BCL2 inhibitors to endocrine therapy that includes a CDK4/6 inhibitor. He and his team will also investigate the effects of targeting MCL1, a BCL2 family member, on tumor response.

Biography

Dr. Lindeman, a clinician-scientist, is Joint Head of the Stem Cells and Cancer Division at the Walter and Eliza Hall Institute of Medical Research (‘WEHI’); medical oncologist at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital; Professorial Fellow in the Department of Medicine, University of Melbourne; and leads the NHMRC Centre of Research Excellence in Translational Breast Cancer Research.

His laboratory is studying molecular regulators of normal mammary gland development and cancer, with a particular interest in understanding how mammary stem cells and their progeny contribute to the mammary gland development and cancer. The discovery of RANK-positive progenitor cells as a target for breast cancer prevention in BRCA1 mutation carriers influenced the establishment of an international prevention study, BRCA-P. His laboratory is also using patient derived xenograft (PDX) and tumor organoid models to test promising anti-cancer agents, including drugs that target the BCL-2 family.

He is a member of the Scientific Advisory Committee (and former Board member) of Breast Cancer Trials (formerly the Australian and New Zealand Breast Cancer Trials Group) and member of the Executive of kConfab (a familial breast cancer consortium). Awards include the Ramaciotti Medal for Excellence in Biomedical Research (2016) and Victoria Prize for Science and Innovation (2017), jointly awarded with Dr Visvader. He has been elected Fellow of the Australian Academy of Health and Medical Sciences (2015) and the Australian Academy of Science (2016)

BCRF Investigator Since

2018