New technique predicts gene resistance to cancer treatments

February 21, 2018 by Rosalind D'eugenio, Yale University
New technique predicts gene resistance to cancer treatments
Credit: Yale University

Yale School of Public Health researchers have developed a new method to predict likely resistance paths to cancer therapeutics, and a methodology to apply it to one of the most frequent cancer-causing genes.

That gene, KRAS, is mutated in approximately 20 percent of all human cancers and has a major presence in pancreatic, colorectal and lung cancers, can continue to mutate and evolve even after successful chemotherapy, radiation or drug treatment.

The study, published in Oncogene , follows up on new targeted therapies that show promise in inhibiting the KRAS G12C variant. Researchers collaborated with Gilead Sciences in Foster City, California to perform sequencing of KRAS-positive lung tumors to determine the prevalence of other oncogenic that could lead to treatment resistance. They were also able to assess new mutations in KRAS itself that could present after treatment of specific tumors.

"The initially appears to successfully target a specific mutation in KRAS," said Jeffrey Townsend, Ph.D., the Elihu Associate Professor of Biostatistics at the Yale School of Public Health and associate professor of ecology and evolutionary biology at Yale. "But, other mutations can appear down the road. By assessing the 's potential to reinvent itself after , our findings inform us on how to combine therapies to intervene before comes back in full force."

The researchers focused on getting ahead of potential new tumor development by preventing resistance and inhibiting the KRAS G12C mutation. The study findings offer insight into new mutations likely to resist treatments based on the degree that specific mutations drive the growth and evolution of cancer, and the potential of therapeutic that may be able to stop deviant gene function.

"Currently, we treat tumors with medication to target and inhibit the tumor as is, but not to prevent the future evolution of tumors into resistant forms," said Townsend. "We need to develop techniques and drugs that not only target the mutations that we know are there, but that also stop the evolution of the tumor."

Using a national database of tumor sequences along with tumor sequences from previous Yale studies, the researchers created a promising evolutionary framework with potential utility in prediction of pathways to resistance to new targeted therapies as they become available. By judicious combinations of multiple therapies that prevent the emergence of resistant forms, the researchers predict that cancer can eventually be overcome.

Explore further: Editing genes one by one throughout colorectal cancer cell genome uncovers new drug target

More information: Vincent L. Cannataro et al. Heterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C, Oncogene (2018). DOI: 10.1038/s41388-017-0105-z

Related Stories

Editing genes one by one throughout colorectal cancer cell genome uncovers new drug target

September 27, 2017
Cancers driven by mutations in the KRAS gene are among the most deadly. For decades, researchers have tried unsuccessfully to directly target mutant KRAS proteins as a means to treat tumors. Instead of targeting mutant KRAS ...

Gene duplication explains tumor aggressiveness

January 31, 2018
Pancreatic cancer is a form of cancer associated with the highest mortality rates in the world. Genetic changes that could explain its aggressiveness and early metastasis are elusive. A team at Technical University of Munich ...

Researchers develop new strategy to target KRAS mutant cancer

September 14, 2017
Although KRAS is one of the major oncogenes associated with aggressive cancers, drugs designed to block KRAS function have not been able to halt cancer progression in a clinical setting. Until now, KRAS has remained infamously ...

Discovery of a new gene critical in the development of lung and pancreatic cancers

February 22, 2017
Researchers at the Center for Applied Medical Research (CIMA) of the University of Navarra have identified a critical gene, FOSL1, in the development of lung and pancreatic cancer. The results of the work, a collaboration ...

KRAS gene mutation and amplification status affects sensitivity to antifolate therapy

April 4, 2012
Testing patients with non-small cell lung cancer for both mutations and amplifications of the KRAS gene prior to therapy may help to predict response to treatment with antifolates, according to the updated results of a preclinical ...

Recommended for you

Revealing the molecular mystery of human liver cells

October 22, 2018
A map of the cells in the human liver has been created by University Health Network Transplant Program and University of Toronto researchers, revealing for the first time differences between individual cells at the molecular ...

New drug combination destroys chemo-resistant blood cancer

October 22, 2018
Researchers from The Ottawa Hospital and the University of Ottawa have developed a promising targeted strategy to treat chemotherapy-resistant acute myeloid leukemia (AML) and a diagnostic test to determine which AML patients ...

New tool gives deeper understanding of glioblastoma

October 22, 2018
Researchers in the lab of Charles Danko at the Baker Institute for Animal Health have developed a new tool to study genetic "switches" active in glioblastoma tumors that drive growth of the cancer. In a new paper in Nature ...

RNA thought to spread cancer shows ability to suppress breast cancer metastasis

October 22, 2018
Researchers at The University of Texas MD Anderson Cancer Center have discovered that a form of RNA called metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appears to suppress breast cancer metastasis in mice, ...

Targeting a hunger hormone to treat obesity

October 22, 2018
About 64 per cent of Canadian adults are overweight or obese, according to Health Canada. That's a problem, because obesity promotes the emergence of chronic diseases such as type 2 diabetes, heart disease and some cancers.

Major trial shows targeted drug extends breast cancer survival

October 22, 2018
Combining a targeted drug with hormone therapy substantially extends survival for women with advanced breast cancer, a major clinical trial has found.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.