Next Generation Chemistry Centers for Fusion Oncoproteins (UM1 Clinical Trial Not Allowed)

NCI is forming the Targeting Fusion Oncoproteins in Childhood Cancers (TFCC) Network to advance our understanding of the mechanisms of action of fusion oncoproteins in pediatric cancers and to apply novel chemical strategies for developing targeted therapeutic approaches. This RFA will use the UM1 mechanism to fund Next Generation Chemistry Centers (NGC) for Fusion Oncoproteins that have independent research projects using innovative chemical biology technologies and chemoproteomic approaches to target fusion-driven cancers. The goal of these discovery efforts will be to identify and develop small molecules that effectively disrupt fusion oncoproteins through mechanisms including, but not limited to, inhibiting activities of individual fusion oncoproteins, blocking critical fusion protein interactions, interacting with coding and/or noncoding RNAs required for fusion protein oncogenesis, and selectively inducing fusion protein degradation or degradation of proteins representing critical fusion oncoprotein dependencies. Compounds envisaged to be derived from these efforts may be either at the level of chemical probes and tools to delineate underlying biology, advanced leads to support further optimization to a candidate, or potential drug candidates themselves. In addition to the research proposed in their applications, each NGC Center will be expected to participate in collaborative projects with the U01s and potentially other members of the fusion oncoprotein community. Funding priority will be given to applications that focus on fusion oncoproteins found in tumors that have high risk of treatment failure and for which there has been little progress in identifying targeted agents. Applications focused on high-risk pediatric solid tumors and brain cancers are particularly encouraged. UM1 recipients will meet regularly with U01 grantees funded through the Mechanisms of Fusion-Driven Oncogenesis in Childhood Cancers FOA.