Thanks to the continued generosity of the Holden Family, Holden Comprehensive Cancer Center is able to support the development of multi-investigator team science to address important research questions in cancer. This award honors the memory of the late James Mezhir, MD, a former member of the cancer center who died in 2016.

Dawn Quelle, PhD, Professor of Neuroscience and Pharmacology, and a multi-disciplinary team of cancer biologists, pathologists, geneticists, epidemiologists and medical oncologists, received a second year of Mezhir Award support for their project, “Targeting RB1 Pathway in NF1 Tumors.” This translational study is focused on advancing our understanding of the RABL6A-RB1 cancer pathway in malignant peripheral nerve sheath tumors (MPNSTs) and initiating a clinical trial using FDA-approved inhibitors of cyclin-dependent kinases for sarcoma patients. MPNSTs are an aggressive sarcoma and leading cause of death in patients with the neurological tumor syndrome, neurofibromatosis type 1 (NF1).  Children and adults with MPNSTs lack beneficial treatment options. Current MPNST therapies, which include surgical resection of the tumors and chemoradiotherapy, are debilitating and ineffective. Through this collaborative work, the group seeks to 1) identify clinically meaningful biomarkers of the transition from benign neurofibromas to malignant tumors, 2) establish the role and utility of RABL6A as a therapeutic target in MPNST using mouse tumor models, and 3) lay the groundwork (design a trial, obtain Pharma support and IRB approval) to begin a clinical trial using rational combination therapy in patients with sarcoma (including MPNST) and other NF1 mutant cancers.