DFCI-002-06

**DFCI-002-06** is a novel bifunctional PROTAC (proteolysis-targeting chimera) developed by Dana-Farber Cancer Institute as a dual degrader targeting Bruton tyrosine kinase (**BTK**) and hematopoietic cell kinase (**HCK**). It induces potent degradation of both kinases, bypassing ibrutinib resistance mutations such as BTK C481S commonly seen in B-cell malignancies. Preclinical studies demonstrate robust degradation in MYD88-mutated xenograft models, with potent anti-tumor activity in Waldenström macroglobulinemia (**WM**) and other MYD88-driven lymphomas. It remains in early-stage research without reported clinical trials.[1][5][9][11]