Seminar Series: Xiaobing Shi

Xiaobing Shi, Professor, in the Epigenetics department at Van Andel Institute, will be a speaker for the Purdue Institute for Cancer Research 2025-26 Seminar Series. This event is hosted by Rong Huang.

Seminar Details

Epigenetic Regulation of Drug Resistance in Cancer

Melanoma is a highly aggressive skin cancer, with approximately 50% of cases harboring activating mutations in the BRAF gene, most commonly the V600E variant. This mutation drives constitutive activation of the MAPK/ERK signaling pathway, promoting unchecked cell proliferation and survival. Targeted therapies using BRAF inhibitors (BRAFi), such as vemurafenib and dabrafenib, have significantly improved outcomes for patients with BRAF-mutant melanoma. However, despite initial responses, most patients eventually develop resistance, posing a major clinical challenge.

Resistance mechanisms include MAPK pathway reactivation via secondary mutations (e.g., in NRAS or MEK), receptor tyrosine kinase upregulation, and activation of alternative pathways such as PI3K-AKT. Non-genetic factors, including epigenetic alterations and tumor microenvironment influences, also contribute to adaptive resistance. Notably, genes encoding epigenetic regulators are frequently mutated in BRAF-mutant melanoma, suggesting a potential epigenetic basis for intrinsic or acquired resistance. In this presentation, I will discuss potential epigenetic mechanisms underlying BRAFi resistance and emerging therapeutic strategies aimed at overcoming drug resistance and improving patient outcomes.