The Walter and Eliza Hall Institute of Medical Research Victoria, Australia
Joint Division Head, Cancer Biology and Stem Cells Division
Improving the effectiveness of therapies for women with estrogen receptor-positive breast cancer.
About one quarter of women with early-stage, estrogen receptor (ER)-positive breast cancer will later be diagnosed with metastatic breast cancer (MBC). 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 investigating drugs that target the survival proteins that help keep cancer cells alive as a potential treatment option for women with ER-positive breast cancer that is no longer responding to the combination therapy.
Dr. Lindeman’s team conducted laboratory studies of the combination of an inhibitor of survival protein BCL2 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. The team observed promising activity in a phase I clinical trial testing a BCL2 inhibitor and hormone therapy in patients with metastatic breast cancer. Now, they are conducting a phase I trial called PALVEN combining BCL2 inhibitor with CDK4/6 inhibitor and have identified a safe and tolerable dose that can be used for later phase studies. Dr. Lindeman and his team are also extending pre-clinical modeling to test novel inhibitors of other BCL2 family survival proteins, BCL-XL and MCL1, which have thus far proven elusive as therapeutic targets.
Over the upcoming year, Dr. Lindeman and his team will analyze results of the PALVEN trial and carry out translational work on samples. The team will continue pre-clinical modeling of BCL-XL inhibitors, which includes the design of novel pre-clinical compounds.
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)
2018
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