Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

UTSW Cancer Researchers Identify Irreversible Inhibitor for KRAS Gene Mutation

Published: Tuesday, July 29, 2014
Last Updated: Monday, July 28, 2014
Bookmark and Share
Irreversible inhibitor for KRAS gene mutation involved in lung, colon, and pancreatic cancers.

UT Southwestern Medical Center cancer researchers have found a molecule that selectively and irreversibly interferes with the activity of a mutated cancer gene common in 30 percent of tumors.

The molecule, SML-8-73-1 (SML), interferes with the KRAS gene, or Kirsten rat sarcoma viral oncogene homolog. The gene produces proteins called K-Ras that influence when cells divide. Mutations in K-Ras can result in normal cells dividing uncontrollably and turning cancerous. These mutations are particularly found in cancers of the lung, pancreas, and colon. In addition, people who have the mutated gene are less responsive to therapy.

Researchers have unsuccessfully tried to develop a drug to inhibit K-Ras for some 30 years.

“RAS proteins including KRAS have not been ‘druggable’ for many decades despite a lot of effort from academia and industry,” said senior author Dr. Kenneth Westover, Assistant Professor of Radiation Oncology and Biochemistry, and a member of UT Southwestern’s Harold C. Simmons Cancer Center.

“We are exploring irreversible inhibitors as a solution, which we believe may pave the way for the development of KRAS-targeted compounds with therapeutic potential and perhaps compounds that target other RAS family proteins involved in cancer,” Dr. Westover said.

Dr. Westover works as both a clinician as a member of the Lung Radiation Oncology Team at the Simmons Cancer Center, and as a researcher. The Westover laboratory investigates the molecular basis of cancer with an eye toward developing compounds that perturb cancer biology, and therefore have potential to become therapies. Dr. Westover’s lab has been particularly targeting KRAS because this gene is the most commonly mutated oncogene in cancer.

Building on previous work, Dr. Westover and fellow investigators used a technique called X-ray crystallography to determine what happens when SML is added to KRAS carrying the G12C mutation, a hallmark of tobacco-associated lung cancer and present in 25,000 of the new cases of lung cancer in the U.S. annually.

Researchers found that SML irreversibly binds to mutated KRAS, making the KRAS G12C inactive. SML competes with molecules that KRAS naturally binds to, called GTP and GDP, and is not removable, even when GTP and GDP are present at very high levels. This attribute is what makes SML an irreversible inhibitor - neither GDP nor GTP are able to knock it off and take its place.

The researchers then used a technique called mass spectrometry to determine that SML is not only irreversible, but selective - binding only to KRAS and not the roughly 100 other members of the RAS protein family that have very similar structures.

“We believe SML may be the first irreversible and selective inhibitor of KRAS,” said Dr. Westover, who was recruited to UT Southwestern with funds from the state-funded Cancer Research and Prevention Institute of Texas. “As a next step, we are improving the SML compound to facilitate studies involving living cancer cells, and eventually animals and humans.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,300+ scientific posters on ePosters
  • More than 4,900+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

New Therapeutic Targets For Small Cell Lung Cancer Identified
Researchers at UTSW Medical Center have identified a protein termed ASCL1 that is essential to the development of small cell lung cancer.
Friday, July 22, 2016
New Method Detects Telomere Length for Research into Cancer, Aging
UT Southwestern Medical Center cell biologists have identified a new method for determining the length of telomeres, the endcaps of chromosomes, which can influence cancer progression and aging.
Friday, July 01, 2016
Enzyme Link Between Excessive Heart Muscle Growth, Cancer Growth
Researchers at UTSW have found that the drugs currently used to inhibit these enzymes in cancer may also be effective in treating enlargement of the heart muscle.
Saturday, April 16, 2016
Treatment of Common Prostate Cancer
Researchers at UTSW have found that the prostate cancer treatments suppress immune response and may promote relapse.
Friday, April 08, 2016
A Metabolic Twist that Drives Cancer Survival
A novel metabolic pathway that helps cancer cells thrive in conditions that are lethal to normal cells has been identified.
Friday, April 08, 2016
Novel Metabolic Twist that Drives Cancer Survival
Researchers at CRI at UT Southwestern have identified a novel metabolic pathway that helps cancer cells thrive in conditions that are lethal to normal cells.
Thursday, April 07, 2016
Structure of Crucial Enzyme Identified
Researchers at UTSW have determined the atomic structure of an enzyme that plays an essential role in cell division and better treatment of cancer.
Thursday, March 31, 2016
Mutation That Causes Rare Disease
A mutation has been discovered that causes a rare systemic disorder known as XLPDR and confirmed a role for nucleic acids in immune function.
Tuesday, March 29, 2016
Promoting Liver Tissue Regeneration
Researchers at CRI have reported that inactivating a certain protein-coding gene promotes liver tissue regeneration in mammals.
Saturday, March 26, 2016
Lupus Study Shows Precision Medicine’s Potential to Define the Genetics of Autoimmune Disease
Researchers at UT Southwestern have used next-generation DNA sequencing technology to identify more than 1,000 gene variants that affect susceptibility to SLE.
Saturday, March 19, 2016
Researchers Find New Cytoplasmic Role
Researchers at UT Southwestern Medical Center have found new cytoplasmic role for proteins linked to neurological diseases, cancers.
Friday, March 18, 2016
Researchers’ Work Shines LIGHT on how to Improve Cancer Immunotherapy
Researchers at UT Southwestern Medical Center have reported a strategy to make a major advancement in cancer treatment.
Thursday, March 17, 2016
CRI Develops Innovative Approach for Identifying Lung Cancer
Institute has developed innovative approach for identifying processes that fuel tumor growth in lung cancer patients.
Tuesday, February 09, 2016
HIV Protein Manipulates Hundreds of Human Genes
Findings search for new or improved treatments for patients with AIDS.
Thursday, January 28, 2016
UT Southwestern Scientists Synthesize Nanoparticles
Synthetic nanoparticles to deliver tumor-suppressing therapies to damaged livers.
Wednesday, January 27, 2016
Scientific News
Liquid Biopsies: Miracle Diagnostic or Next New Fad?
Thanks to the development of highly specific gene-amplification and sequencing technologies liquid biopsies access more biomarkers relevant to more cancers than ever before.
Gene Terapy for Muscle Wasting Developed
New gene therapy could save millions of people suffering from muscle wasting disease.
Gene-Editing 'Toolbox' Targets Multiple Genes Simultaneously
Researchers have designed a system that modifies, or edits, multiple genes in a genome at once while minimising unintentional effects.
Discovering the First Farmers
Genetic analyses reveal a collection of highly distinct groups in the Near East and Europe at the dawn of agriculture.
Fighting Cancer Through Protein Pathways
Researchers have found a new drug target within a protein production pathway critical to regulating growth and proliferation of cells.
Mutations in DNA-Repair Genes Found in Advanced Prostate Cancers
New findings indicate that nearly 12% of male advanced prostate cancer sufferers have inherited mutation in DNA-repair genes.
Ice Bucket Challenge Instrumental in Gene Discovery
Donations from the ALS Ice Bucket Chellenge allowed for the largest-ever study of inherited ALS, which identified a new ALS gene.
Triple-Action Therapy Patch Shows Promise
Patch that delivers drug, gene, and light-based therapy to tumor sites shows promising results in mice.
Cancer Gene-Drug Combinations Ripe for Precision Medicine
The study aims to expand the number of cancer gene mutations that can be paired with a precision therapy.
Targeting BRAF Mutations in Thyroid Cancer
Treating metastatic thyroid cancer patients harboring a BRAF mutation with vemurafenib showed anti-tumor activity in a third of patients.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!