# Admin-Core-001

> **NIH NIH P01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $74,339

## Abstract

The RAS oncogenes (HRAS, KRAS and NRAS) comprise the most frequently mutated oncogene family in
cancer. Despite more than three decades of intensive effort, presently no effective RAS-targeted therapies
have reached the clinic. Contributing to this failure have been missteps and mistakes made in drug
development, resulting from the field underestimating the complexities of RAS. While recent cancer genome
sequencing studies have provided a more comprehensive genetic portrait of specific cancers, they have also
verified that RAS mutations are the major drivers of cancers that comprise three of the four major causes of
cancer deaths in the US (lung, colorectal and pancreatic cancer). A “RAS Renaissance” has now begun, with
renewed intense interest and effort to identify and develop new pharmacologic strategies to target aberrant
RAS function for cancer treatment. Our rationale for this Program Project is based on our belief that key
issues regarding RAS function remain to be resolved and that their resolution will be vital to facilitate more
knowledgeable and effective approaches for anti-RAS drug discovery. Our overall premise is that RAS
mutations are not created equal. Our overarching hypotheses are that there are significant differences among
RAS isoforms and RAS mutations, and that these have distinct oncogenic consequences in different cancers.
Four Projects comprise our P01, each led by a long-standing RAS researcher who brings complementary and
distinct experimental expertise to a Program designed for strong inter-project collaborations that leverage our
strengths and minimize our weaknesses. Collectively, we will produce a cohesive and comprehensive study
that could not be achieved by individual laboratories working on their own. Our structural, biochemical and
biological efforts will identify RAS isoform- and mutation-specific perturbations to RAS function. In the long
term, these distinct perturbations may represent targetable vulnerabilities that will reveal new approaches to
develop mutation-specific anti-RAS therapies for cancer treatment. Project 1 focuses on cellular studies of
KRAS mutations in pancreatic cancer, closely coordinated with the structural and biochemical studies of KRAS
in Project 2. Project 2 studies of NRAS are complemented by Project 3 studies of mutant NRAS and wild type
RAS alleles in melanoma. Project 4 will use genetically engineered mouse models of lung cancer to address
the basis for the preferential mutation of KRAS in cancer. Core A will provide financial oversight, administrative
coordination of information exchange, and biostatistics support across this inter-institutional Program Project.
Core B will provide innovative proteomics technologies for unbiased profiling of RAS mutation-selective
effector signaling. Our Program findings will help to reshape anti-RAS drug discovery with the goal of
developing therapies targeting specific subsets of RAS mutations. Relevance to Public Health: RAS mutations
are ver...

## Key facts

- **NIH application ID:** 10025416
- **Project number:** 5P01CA203657-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** CHANNING J. DER
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $74,339
- **Award type:** 5
- **Project period:** — → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025416

## Citation

> US National Institutes of Health, RePORTER application 10025416, Admin-Core-001 (5P01CA203657-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10025416. Licensed CC0.

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