Titles and Affiliations
Senior Principal Research Fellow and co-Leader of the Cancer Ecosystems Program in the Garvan Institute of Medical Research, Sydney Australia
Professor in the Faculty of Medicine, UNSW Sydney
Leadership Fellow National Health and Medical Research Council of Australia
Research area
Reprogramming cells in the tumor microenvironment to overcome treatment resistance.
Impact
Many breast cancer cells evolve to resist treatment by hijacking normal connective tissue cells, turning them into cancer-associated fibroblasts (CAFs) that shield the cancer from immune attack. Previous attempts to simply eliminate these cells have failed and, in some cases, worsened outcomes. Dr. Swarbrick is pursuing a different strategy: reprogramming these cells rather than destroying them and turning them from immune-suppressing barriers back into harmless tissue cells.
Progress Thus Far
Dr. Swarbrick and his team screened more than 13,000 compounds for their ability to reverse the harmful behavior of CAFs in laboratory models. The screen identified a drug candidate already approved for use in kidney disease that showed early promise in reducing the fibroblasts’ ability to block immune cells from attacking the tumor. In parallel, the team analyzed roughly 367,000 individual cells from 57 patient tumors and mapped the specific cellular patterns associated with treatment resistance and response. They achieved high accuracy in predicting whether a patient would respond to neoadjuvant chemotherapy. This analysis confirmed that specific CAF types play a central role in protecting cancer from treatment by creating an immunosuppressive environment, particularly in patients who don’t respond well to chemotherapy. The team also found that chemotherapy itself triggers notable changes in a tumor’s blood vessels and made progress understanding how cancer-fighting immune cell clusters form and mature within tumors.
What’s next
Dr. Swarbrick’s team will prioritize and rigorously test their strongest candidate drugs to determine how effectively they can reprogram CAFs and restore immune function in breast cancer laboratory models. The goal is to break down the immune barrier created by CAFs, potentially allowing immunotherapies to work for the many breast cancer patients who currently don’t respond to them.
Biography
Alexander Swarbrick, PhD completed his PhD at University of New South Wales, followed by a postdoctoral fellowship with Nobel Laureate J. Michael Bishop at UC San Francisco. Dr. Swarbrick studies breast cancers as complex cellular ecosystems, aiming to understand the way that cellular interactions impact tumor behavior. He is a leader in the application of single-cell & spatially-resolved ’omics to human disease, which he uses to discover new ways to predict the behavior of a patient’s cancer and novel treatments for patients unlikely to benefit from established therapies. Dr Swarbrick is chair of the Cancer Council NSW cancer research committee and co-convenor of the Australian Translational Breast Cancer Research Symposium.
