Federal Grant Award Summary

H. Lee Moffitt Cancer Center and Research Institute Hospital, Inc. received a $682,495 Project Grant from the National Cancer Institute (NCI) under the Cancer Biology Research program (CFDA 93.396) to conduct fundamental research on melanoma pathogenesis and treatment. The award, effective June 1, 2026, through May 31, 2031, supports a five-year investigation into the SPOP-BRAF-mTORC1 signaling axis in melanoma development. The research focuses on understanding how SPOP (an E3 ubiquitin ligase) regulates BRAF protein degradation and how SPOP mutations contribute to melanoma progression in both treatment-naive and BRAF inhibitor-resistant cases. Additionally, the project examines the kinase-independent activation of mTORC1 by wild-type and non-V600-mutated BRAF proteins, which may explain why MEK inhibitors show limited efficacy in these melanoma subtypes.

The deliverables from this Cancer Biology Research grant include mechanistic insights into post-translational regulation of BRAF oncogenic function, identification of therapeutic vulnerabilities in melanoma patients with wild-type or non-V600-mutated BRAF mutations, and potential novel treatment strategies for the more than 50 percent of melanoma patients currently lacking effective therapeutic options. This fundamental research is expected to advance understanding of cancer mechanisms and ultimately provide better methods for prevention, detection, diagnosis, and treatment of melanoma, consistent with the Cancer Biology Research program's mandate to support investigative work on cancer development and progression.