RAS Initiative

The RAS Initiative mobilizes the cancer research community to develop ways to treat cancers driven by the mutant RAS gene in an open model of collaboration among government, academic, and industry researchers.
People per year in the U.S. are diagnosed with cancers caused by KRAS mutations.
What is this? Surface representation of the structure of an oncogenic mutant of KRAS in complex with RAS-binding domains of RAF1 Kinase. The GMPPNP bound to oncogenic KRAS mutant is shown in ball-and-stick representation.

The National Cancer Institute RAS Initiative endeavors to better understand the RAS oncogene and discover its vulnerabilities to treat RAS-related cancers. 

About one-third of all human cancers are driven by mutations of the RAS family of genes.  

Though scientists have known about RAS for more than 30 years, a treatment to block the oncogene has been elusive. 

Our scientists investigate approaches to RAS-driven cancer from multiple angles and multiple fields. From protein production to assay development to structural discoveries, we contribute to the search for an effective RAS inhibitor. 

Creating community to progress the field

When the National Cancer Institute RAS Initiative was founded in 2013, researchers studying mutated RAS proteins were decentralized, scattered across government and academic laboratories. Most major pharmaceutical companies had suspended or avoided drug development for RAS-related cancers because of the cost and poor chance of success. 

Due to scientific limitations at the time, there was no obvious path to better understand the mutant proteins’ behavior in human cells or to discover treatments for the thousands of RAS-related cancers. But the fledgling project headquartered at the Frederick National Laboratory soon began to turn heads. 

Through an open, collaborative model and under the guidance of the National Cancer Institute, we developed a united, international RAS research community.  

The RAS Initiative’s aspirational goals and early progress, along with headway made by other groups, helped to reignite interest and inspire laboratories and industry to renew the search for treatments. Funded by the National Cancer Institute, the initiative continues to pursue progress in basic research and drug discovery for RAS-related cancers. 

Research teams

Frederick National Laboratory researchers work together toward the initiative's goals. The RAS Initiative is comprised of nine teams:

Biochemistry & Biophysics

The team uses a variety of biochemical and biophysical assays to characterize the interaction between RAS proteins and their effectors in solution or on the membrane. Our researchers also develop assays to identity small molecules inhibitors of RAS.

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The team provides data processing and analytical support and creates software tools to organize and interpret data produced by the RAS Initiative.

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The team uses fragment-based drug discovery approaches to develop low molecular weight screening hits, known as fragments, into potent inhibitors with favorable drug-like properties.

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Computational Chemistry

The team uses computers to aid in drug discovery. Our main tool is the software package UCSF DOCK, which we use for performing large-scale screens of hundreds of millions—soon to be billions—of molecules.

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Drug Screening and Preclinical Research

The team strives to discover and develop compounds that directly target oncogenic RAS proteins.

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The team develops and applies new optical microscopy techniques to understand how RAS molecules move, interact, and signal in living cells.

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Mass Spectrometry

The team employs cutting-edge protein analysis methods to better understand and target canonical RAS isoforms, RAS-related proteins, and RAS-dependent signaling pathways.

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The team supplies nucleic acids, cell lines, and protein reagents for the RAS Initiative. We support the development of structural studies, drug screens, imaging experiments, and cell biology and biochemistry projects. 

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Structural biology

The team leads efforts on the structural characterization of RAS complexes to provide new structural and mechanistic insights into RAS biology and to identify new targets for structure-based drug discovery efforts.

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We collaborate with other institutions and experts, including Frank McCormick from the University of California, San Francisco, a key RAS Initiative consultant. Some of our laboratories, such as the Protein Expression Laboratory, are part of the RAS Initiative groups.

The Frederick National Laboratory provides reagents to the research community and coordinates a biennial RAS Symposium to elevate progress and unite scientists in the field.