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Isaac Chan, MD, PhD
Medical Oncology Fellow
Johns Hopkins University
Conquer Cancer Foundation of ASCO
Goal: Developing new immunotherapeutic strategies to treat metastatic breast cancer.
Impact: Metastasis is the primary cause of breast cancer deaths. Immunotherapy with anti-PD-L1 agents has helped some patients with metastatic breast cancer (MBC), but most patients to not benefit from current immunotherapies. Dr. Chan is testing a different approach to immunotherapy that may be more effective than PD-L1 directed therapies.
What’s next: Dr. Chan has discovered that metastatic breast cancer cells can convert cancer-killing immune cells into tumor-promoting immune cells. He will conduct laboratory studies using sophisticated systems to study how MBC cells interact with immune cells that would normally launch an anti-tumor attack. To counter this effect, he will test a drug that shuts down the tumor-promoting immune cells.
Metastatic breast cancer occurs when cancer cells escape the original tumor, enter the circulation, and become established in a distant tissue. Most breast cancer cells do not survive this journey due, in part, to the immune system. Tumor cells have ways to co-opt other cells to promote their survival. Dr. Chan’s research has shown that they do this with immune cells called natural killer (NK) cells that would normally launch an attack against the tumor. He will study how MBC cells interact with NK cells to cause them to become tumor-promoting NK cells.
Full Research Summary
Research area: To understand how metastatic breast cancer (MBC) cells subvert the immune system to promote metastatic tumor growth.
Impact: Metastatic breast cancer is currently an incurable disease. Some MBC patients have benefitted from current immunotherapies, but most patients do not respond. This may be due, in part, to a lack of immune cells called T-cells in breast cancers, suggesting that T-cells are not the immune effector cells in breast cancer. Another type of immune cell called natural killer (NK) cells also have potent anti-tumor activity, but MBC cells can turn the tumor-killing NK cells into tumor-promoting NK cells. Dr. Chan is exploring how best to harness the anti-tumor activity of NK cells with targeted therapies that prevent their conversion by MBC cells.
Current investigation: Dr. Chan will employ a sophisticated, 3-dimensional cell-culturing model to study how NK cells and metastatic breast cancer cells interact. He found that NK cells can limit early stages of metastasis by killing specific types of metastatic breast cancer cells. After prolonged exposure to MBC cells, however, NK cells turn into tumor-promoting cells. In his Conquer Cancer Foundation research supported by BCRF, Dr. Chan will investigate potential strategies to prevent the conversion of NK cells to tumor-promoting NK cells with a targeted therapy that is currently in clinical trials.
Dr. Isaac S. Chan received his Bachelor of Science in Engineering degree from Duke University in 2005 and then went on to pursue a dual MD/PhD degree from the University of North Carolina, where he was a James Moses and Stella Frosst Alexander Scholar. In the lab of Dr. Anna Mae Diehl, he worked on how dysregulated Hedgehog signaling in the liver microenvironment drives hepatocellular carcinogenesis.
After medical school, he completed an internship and residency in Internal Medicine at Boston University and then went on to pursue subspecialty training in medical oncology at Johns Hopkins University. For his postdoctoral studies, he joined the laboratory of Dr. Andrew Ewald to continue his research focus on the tumor microenvironment and how it impacts carcinogenesis. There he developed new models to discover how breast cancer cells can alter the immune microenvironment to support metastasis. For his work, he was named a 2019 MacMillan Scholar at Johns Hopkins.
He is grateful for the support of the CCF YIA in Breast Cancer and is eager to continue working on new therapies that can target the tumor immune microenvironment toward the goal of preventing metastatic breast cancer.