Advancing RAS and RASopathy Therapies

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

In FY 2019, a group of investigators from CCR and DCEG successfully competed for funding for a new NCI initiative for the RASopathies. With this funding, we assembled a multi-disciplinary group of international RASopathy experts at a project kick-off meeting in February 2019. As a result of this meeting, we have produced a longitudinal cohort study for patients with non-NF1 RASopathies that will be conducted through DCEG. This protocol was recently approved by the CIRB and is currently enrolling. The goals of this trial are to prospectively study the incidence of cancer development in these patients but also to identify specific measurable endpoints that can be used for monitoring the success or failure of interventional trials. Potential first interventional trials were identified, and appropriate industry contacts have been made, including a CRADA with Kura Oncology for the use of tipifarnib in Costello syndrome. In addition to the clinical protocol, we also have initiated several preclinical studies to evaluate the efficacy of RAS-targeting agents in RASopathies. We plan a study of tipifarnib in an HRASG12S model of Costello syndrome and a study of mirdametinib in a MEKY30C model of CFC. These studies will be conducted in collaboration with CAPR and Dr. Lino Tessarollo. Finally, in a population genomics effort headed by Dr. Douglas Stewart, we aim to identify new RASopathy variants and genes. This project has begun, and newly identified variants will be functionally validated in the Yohe lab.