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Geoffrey Lindeman, MBBS, FRACP, PhD
Joint Division Head, Stem Cells and Cancer
The Walter and Eliza Hall Institute of Medical Research
- Seeking to improve the effectiveness of cancer therapies for women with ER-positive and other types breast cancer.
- Testing the safety and efficacy of a new class of drug that switch off key ‘survival’ proteins that keep breast cancer cells alive.
- These studies have important implications for boosting the response to therapy and improving outcomes for women with relapsed ER-positive breast cancer.
About 25 percent of patients with early stage breast cancers will be diagnosed with metastatic breast cancer. New treatments are urgently needed for this incurable disease. Dr. Lindeman is testing the safety and effectiveness of combining a targeted therapy approved for the treatment of leukemia with anti-estrogen therapy and CDK4/6 inhibitors in women with metastatic ER-positive breast cancer.
Full Research Summary
Breast cancers that require estrogen to grow–called estrogen receptor (ER)-positive–are the most common subtype of breast cancer. While early stage, ER-positive breast cancers are treatable with anti-estrogen therapies (tamoxifen, aromatase inhibitors and fulvestrant are examples) about one quarter of women diagnosed with early stage ER-positive breast cancer will later be diagnosed with metastatic disease– an incurable form of breast cancer that has spread to other tissues. There is an urgent need for targeted therapies to prevent and treat metastatic breast cancer.
Most ER-positive breast cancers contain high levels of BCL-2, a ‘survival’ protein that helps keep cancer cells alive. Neutralizing BCL-2 proteins could present a new strategy for boosting response to anti-estrogen therapy.
Dr Lindeman’s research is currently focused on exploring how BCL-2 and other family members can be targeted to make cancer therapy more effective. A potent inhibitor of BCL-2, venetoclax, has recently shown tremendous promise in treating blood cancers. His group is currently conducting the first clinical trial of venetoclax (combined with tamoxifen) in breast cancer, with promising findings.
Using laboratory models his team is investigating the safety and effectiveness of combining venetoclax with other types of anti-estrogen therapy and inhibitors of the cell growth (known as CDK4/6 inhibitors). Their research should shed light on how to best combine these drugs and provide a framework for taking this new class of drug to the clinic for patients with breast cancer.
Results from this study have important implications for patients with metastatic ER+ breast cancer, where the hope is to produce deeper and more durable responses that improve patient outcomes
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