Integrating bench-to-bedside and bedside-to-bench research

These two aspects of Chan’s research synergize with each other and help in expediting hypothesis-driven research toward clinical translation. Tissue samples collected from the patients enrolled in clinical trials allow Chan and his team to perform robust tests and another round of hypothesis-generating research which can potentially lead to more effective large-scale phase III clinical trials. Chan has a translational research team that aims to bridge basic science discoveries to clinical research. As a cancer biologist, Chan always thought along the lines of inducing programmed cell death to eradicate cancer. However, recently Chan discovered that there is a tremendously understudied cell death-induced biology that can modulate therapeutic response. Chan’s team serendipitously discovered that dying cancer cells release a lot of factors that can modulate residual cancer cells and the immune tumor microenvironment. These determine how the dendritic cells prime an effective T cell response to reduce tumor burden during chemotherapy and immune checkpoint blockade therapy. Chan shared these insights in the Cancer Moonshot Seminar Series organized by the National Cancer Institute in April 2023. Chan takes a holistic view to dissect how the interactions between cancer, stromal and immune cells within the tumor microenvironment contribute to therapy resistance using single-cell and spatial biology technologies. His team is focused on investigating how cell death plays a role in modulating therapy resistance via promoting compensatory proliferation and immunosuppression.

According to Chan, “Our lab has evolved to taking a holistic view where we simultaneously study cancer-fibroblast-immune crosstalks within the tumor microenvironment using single-cell RNA sequencing and spatial biology profiling. Together with the Methodist Systems Biology team led by Dr. Stephen Wong, Professor of Computer Science and Bioengineering in Radiology and John S. Dunn Presidential Distinguished Chair in Biomedical Engineering, this unique approach helps us get a holistic view of the whole tumor. Specifically, we look at fibroblasts, how they secrete collagen and activate signaling in the cancer cells to regulate the metastatic cascade as well as therapeutic responses.” Furthermore, Chan’s team is investigating how different molecular markers that define varying differentiation states can be utilized as prognostic markers in sub-typing bladder cancer into clinically relevant sub-types . As a part of the international consortium of bladder cancer experts, Chan aims to sub-classify bladder cancer and investigate how individual sub-types associate with therapeutic responses. Taken together, Chan’s efforts have the potential to lead to more effective, tailored treatment regimens and precision medicine therapies for bladder cancer patients. Bladder cancer is an understudied cancer. Yet, about 82,000 new bladder cancer cases and 16,000 bladder cancer deaths are estimated in 2023 according to the American Cancer Society. Moreover, bladder cancer is the fourth most common cancer in men. Chan is eager to collaborate with clinicians to expedite research and investigator-initiated trials to benefit cancer patients, particularly those suffering from bladder and genitourinary cancers. The wealth of vibrant clinical faculties at Neal Cancer Center, together with Chan’s unique approach of integrating bench-to-bedside and bedside-to-bench research may lead to significant improvements in healthcare delivery, innovation, superior decision-making during drug treatment, and the development of novel drug combinations.