Pharmacologic inhibitors of kinases that drive the cell cycle (cyclin-dependent kinases) have revolutionised the treatment of hormone receptor-positive breast cancer. Now that these agents have been a part of clinical practice for some years, new challenges have arisen – most notably the development of resistance.
Acquired resistance to CDK4/6 inhibitors, commonly used in treating ER-positive/HER2-negative breast cancer, poses a significant clinical challenge. This resistance often develops through various mechanisms, including the loss of tumor suppressor proteins like RB1, amplification of the CDK4 or CDK6 genes, and activation of alternative signaling pathways such as PI3K/AKT/mTOR and MAPK/ERK. These changes enable cancer cells to bypass the G1/S checkpoint control, rendering CDK4/6 inhibitors ineffective.
A/Prof Goel leads a research group that positions itself at the intersection of cell cycle biology, epigenetics, and tumour immunology. He has made seminal insights into the mechanisms underlying the activity of and resistance to cell cycle inhibitory drugs.
Most recently, his team has focused on understanding therapy-induced senescence in cancer and he has been awarded a Snow Medical Fellowship and US DOD Era of Hope Scholar to support this work. A/Prof Goel serves as PI randomised clinical trials in breast cancer, all of which stem directly from his laboratory discoveries. He also served as Chair of the American Society of Clinical Oncology Education Committee in 2022-3.
