Guang Yang, PhD Presentations

WM: Genomic & Treatment Advances

Zachary Hunter, PhD, Guang Yang, PhD, Steve Treon, MD, PhD – Dana Farber Cancer Institute, 2018 Ed Forum
Three researchers discuss how MYD88 and CXCR4 mutations are common in WM with MYD88 activating BTK and HCK in WM cells, both targets of ibrutinib. Ibrutinib produces high response rates and durable responses in relapsed and refractory WM. No complete responses. Mutated CXCR4, aberrant IRAK and BCL2 signaling contribute to intrinsic resistance against ibrutinib. Multiple BTK mutations are common with acquired ibrutinib resistance and trigger ERK1/2 survival signaling. Novel strategies to overcome intrinsic and acquired resistance to ibrutinib, including targeting CXCR4, ERK, IRAK, and BCL2 signaling.