This Project Grant award of $1,918,855.00 from the National Cancer Institute (CFDA 93.396 - Cancer Biology Research) supports research into the molecular mechanisms underlying allele-specific signaling and tumor formation by the NRAS oncoprotein. The Ohio State University, as the prime recipient, will conduct in vitro and in vivo experiments to investigate how different NRAS mutations influence BRAF activation and MAPK pathway signaling, which are critical for melanoma development. The...
The National Cancer Institute (NCI) awarded a 5-year, $315,143 Project Grant under the Cancer Research Manpower (CFDA 93.398) program to The Ohio State University. The grant, titled "CLINICAL TRIAL CONCEPT IN THE ONCOLOGY LANDSCAPE", will fund cancer-related research and career development activities at the university. The project aims to advance understanding of cancer biology, immunology, genetics, and translational medicine, while also training the next generation of cancer...
This Project Grant award from the National Cancer Institute (CFDA 93.396 - Cancer Biology Research) provides $470,464.00 to the Regents of the University of Minnesota to conduct research on the molecular mechanisms underlying paradoxical activation of RAF kinases in cancer. The primary objectives are to: Classify a large set of RAF inhibitors based on their allosteric coupling strengths and conformational effects to unravel the connection between inhibitor binding, conformational change, and RAF...
This Project Grant award, valued at $160,642, was issued by the National Cancer Institute (NCI) under the Cancer Research Manpower (CFDA 93.398) federal grant program. The grant supports research to characterize the role of oncogenic NRAS mutations in modulating the leukemogenesis and therapeutic responsiveness of acute myeloid leukemia (AML) with isocitrate dehydrogenase (IDH) mutations. The principal investigator will utilize genetically engineered mouse models and patient-derived xenograft...
This $463,375 federal Project Grant award from the National Institute of Environmental Health Sciences (NIEHS) under the Environmental Health program (CFDA 93.113) supports research at the H. Lee Moffitt Cancer Center and Research Institute Hospital, Inc. in Tampa, Florida. The research aims to identify and characterize the role of melanin-carbonyl-DNA (MCD) and melanin-carbonyl-protein (MCP) adducts in the progression and treatment resistance of NRAS mutant melanoma. The key objectives are to...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $508,660.00 to the University of Washington to conduct a systematic biochemical analysis of RAF kinase regulation, intracellular function, and pharmacology. The researchers will leverage molecular tools to define pathways that make RAF isoforms sensitive or resistant to ATP-competitive inhibitors, and apply a new RNA barcoding methodology to perform deep mutational scans of the...
This Project Grant award of $356,850 from the National Cancer Institute's Cancer Treatment Research program (CFDA 93.395) supports a research effort led by The Medical College of Wisconsin, Inc. to characterize KRAS and other RAS gene mutations that may confer sensitivity to EGFR inhibitor drugs in colorectal cancer. The overarching goal is to identify additional RAS mutants that could benefit from EGFR-targeted therapies, which are currently limited due to the assumption that RAS mutations...
This federal Project Grant award from the National Cancer Institute (NCI), under the Cancer Treatment Research program (CFDA 93.395), is funding research at New York University (NYU) School of Medicine to investigate the role of the immune microenvironment in melanoma bone metastasis. The $198,103 award, spanning February 1, 2025 to January 31, 2027, will support the development of preclinical murine models to study how melanoma cells infiltrate and modify the bone microenvironment, as well as...
The National Cancer Institute (CFDA 93.398 Cancer Research Manpower) awarded a $183,398 Project Grant to The Ohio State University, with a start date of September 1, 2024 and an end date of August 31, 2027. The grant is titled "Targeting Mitochondrial Oxygen Demand to Overcome Hypoxic Immune Privilege of NSCLC Tumors" and aims to elucidate the mechanisms of hypoxic immune privilege in non-small cell lung cancer (NSCLC) tumors. The research will investigate how targeting tumor hypoxia...
The National Cancer Institute (NCI) awarded a $340,072 Project Grant under the Cancer Research Manpower (CFDA 93.398) program to the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. The grant supports research to evaluate TMU27A, a novel non-nucleoside inhibitor of ribonucleotide reductase (RNR), as a potential treatment for metastatic breast cancer. The researchers will assess TMU27A's ability to induce DNA damage and chromosomal instability in breast cancer...
The National Cancer Institute (NCI) awarded a $111,502 Project Grant under the Cancer Research Manpower (CFDA 93.398) program to The Ohio State University to conduct research on defining the biochemical properties and implications of NRAS mutant-specific BRAF interactions in melanoma. The project aims to elucidate the structural mechanisms by which specific NRAS mutations promote enhanced BRAF activation and MAPK signaling in melanoma, as well as how these mutant-specific NRAS-BRAF interactions influence the potency of RAF inhibitors. The research will utilize in vitro biosensors, cell-based assays, and mouse models to better understand the mutant-specific features of NRAS that facilitate BRAF binding and activation. The goal is to identify novel mutant-specific NRAS-BRAF interfaces that can guide the design of therapeutic approaches for NRAS-mutant cancers and inform the clinical implementation of next-generation RAF inhibitors. The project will be conducted at The Ohio State University from September 2024 through July 2027.