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Geoffrey Lindeman, BSc (Med), MBBS (Hons), FRACP, PhD
Joint Division Head, Stem Cells and Cancer
The Walter and Eliza Hall Institute of Medical Research
Goal: To improve the effectiveness of therapies for women with ER-positive and other types of breast cancer.
Impact: Dr. Lindeman is studying a drug that inhibits a protein that plays a role in estrogen receptor (ER)-positive metastatic breast cancer. In initial clinical trials, the drug, called venetoclax, improved response to tamoxifen and was well tolerated. He continues to test it with other standard drugs. If initial results can be repeated with other drugs, venetoclax could provide a new treatment option for women with ER-positive breast cancer that is no longer responding the therapy.
What’s next: He and his team will investigate the safety and efficacy of combining venetoclax with hormone therapy plus a CDK4/6 inhibitor, the current standard of care for women with metastatic ER-positive breast cancer.
While breast cancers driven by estrogen—referred to as estrogen receptor (ER)-positive—are treatable with hormone therapy, these cancers can become resistant to these drugs. This is often the case when breast cancers have spread—a process called metastasis. Strategies to improve response, such as adding a CDK4/6 inhibitor have extended the lives of many patients with metastatic breast cancer. Dr. Lindeman is investigating other targeted combination approaches to improve outcomes for patients with advanced disease.
Full Research Summary
Research area: Identifying new treatments for women with estrogen receptor (ER)-positive metastatic breast cancer.
Impact: The most common subtype of breast cancer is ER-positive breast cancer, which requires estrogen to grow. Caught early, these cancers are treatable with anti-estrogen therapies such as tamoxifen, aromatase inhibitors, and fulvestrant. However, about one quarter of women diagnosed with early stage ER-positive breast cancer will later be diagnosed with metastatic disease (MBC)—an incurable form of breast cancer that has spread to other tissues. Targeted therapies are desperately needed to prevent and treat MBC. Dr. Lindeman is studying the drug venetoclax, that blocks a survival factor prevalent in many MBCs. If proven effective, venetoclax could be used to boost response to anti-estrogen therapy for patients with advanced disease.
Current investigation: Dr. Lindeman continues his work in looking for rational combination approaches to improve outcome in patients with advanced ER-positive breast cancer. His current investigation is on a targeted drug called venetoclax in combination with the standard therapy for metastatic breast cancer.
What he’s learned so far: Dr. Lindeman’s team conducted the first clinical trial of venetoclax in breast cancer. They found that the addition of venetoclax to tamoxifen was safe, had minimal side effects and elicited remarkable efficacy in women with metastatic ER-positive breast cancer.
What’s next: Dr. Lindeman will conduct laboratory studies of the combination of venetoclax with hormone therapy and with a cell cycle (CDK4/6) inhibitor. They plan to examine mechanisms of tumor response and resistance, determine whether this combination boosts or suppresses the immune system, and test whether there is a role for targeting similar agents in ER-positive breast cancer. They will also initiate a Phase 1 clinical trial to establish the safety and suitable doses for this combination therapy.
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)