Titles and Affiliations
Associate Professor
Group Leader and Medical Oncologist
Peter MacCallum Cancer Center
Research area
Enhancing the benefits of CDK 4/6 inhibitors in breast cancer.
Impact
CDK 4/6 inhibitors are a class of drugs designed to stop cancer cells from dividing and multiplying. They are currently used in combination with endocrine therapy in the treatment of hormone receptor-positive advanced breast cancers. CDK 4/6 inhibitors have also been found to stimulate T cells (a type of cancer-fighting immune cell) in a way that enhances their ability to attack against cancer. Initial trials suggest that this finding may mean that CDK 4/6 inhibitors could be more widely used to treat other breast cancer subtypes, most notably triple-negative breast cancer where the immune system is an attractive therapeutic target.
Progress Thus Far
Dr. Goel and his team have made progress in two major areas. First, they studied “exhausted” T cells, immune cells that are often present inside tumors but lose their cancer-fighting ability over time. Using cutting edge laboratory models, the team found that CDK4/6 inhibitors reduce levels of a molecule that drives this exhaustion, helping restore T cells to a more effective state by activating the retinoblastoma (Rb) tumor suppressor protein, the same target of CDK4/6 inhibitors’ anti-cancer effect. Second, the team completed a study examining how Rb functions inside breast cancer cells and unexpectedly found that Rb doesn’t just switch off genes linked to cell division, it can also help activate genes controlled by the estrogen receptor. This finding helps explain why CDK4/6 inhibitors work particularly well when combined with endocrine therapy and may also shed light on how some patients develop resistance to treatment.
What’s next
Dr. Goel and his team will continue to investigate how Rb controls gene activity in both immune cells and breast cancer cells following CDK4/6 inhibitor treatment. The team will also explore whether two proteins related to Rb behave similarly after treatment, which could reveal additional ways CDK4/6 inhibitors influence how breast cancers respond to therapy.
Biography
Shom Goel, MBBS, PhD is a physician-scientist at the University of Melbourne and Peter MacCallum Cancer Centre. Having completed clinical training in Australia, he spent ten years in Boston where he conducted his doctoral and postdoctoral research at the Massachusetts General Hospital and Dana-Farber Cancer Institute. He returned to Australia in 2019 to start his own independent research group. In addition to maintaining a clinical practice as an oncologist and triallist, he leads a research laboratory that positions itself at the intersection of cell cycle biology, epigenetics, and immunology in cancer. His team’s work at the Peter Mac has been published in Nature Cancer (2021) and Cancer Discovery (2023). Shom serves as either Global PI or Translational PI for several randomized clinical trials in breast cancer, all directly stemming from his laboratory findings. He was appointed Chair of the American Society of Clinical Oncology Education Committee in 2023. Shom is also a recent awardee of a Snow Fellowship and Era of Hope Scholar Award (US Department of Defense).
