Researchers discover new role for mutant proteins in some of the deadliest cancers

Press release

Tuesday, November 11, 2024

These results could lead to new treatments for RAS-induced cancers.

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The RAS mutant releases EZH2 from a complex protein transported from the nuclear to the cytoplasm. Once released, EZH2 promotes the degradation of DLC1, a tumor suppressor. This leads to uncontrolled tumor growth.NCI via biorender.com

The National Institutes of Health and its collaborators have discovered a new way to treat autoimmune diseases. RAS Mutated genes common in cancer may drive tumor growth in addition to their role as signaling proteins on the cell surface. According to the study, published in November 2024, a RAS mutant helps trigger a sequence of events that involves the transport of specific nuclear proteins, leading to uncontrolled tumor growth. Nature Cancer.

RAS The second most commonly mutated gene in cancer is RAS. Mutated RAS proteins play a key role in some of the deadliest cancers, including nearly all pancreatic and colorectal tumors and one-third of lung cancers. Research has shown for decades that mutations in RAS promote tumor growth and development by activating proteins on the surface of cells. This creates a continuous stream of messages telling cells to grow.

This is the first time that the existence of mutations has been demonstrated. RAS Dr. Douglas Lowy is deputy director of the National Cancer Institute at the NIH. He was one of the study's authors. The discovery of an additional role for the RAS protein has exciting implications for improving treatment.

Drugs that block the mutant RAS protein have only been on the market for a short time and are FDA-approved to treat lung cancers and sarcomas. RAS inhibitors, while a scientific advance, have had only a limited impact on patient outcomes. They typically improve survival times by a few weeks.

A group led by Dr Lowy was involved in early studies to identify RAS As a tumor-promoting gene, it helped explain the process of its growth. The research team discovered that the mutant RAS gene was directly involved in the release of a nuclear protein called EZH2 that is transported from the nucleus to the cytoplasm. EZH2 is released and facilitates the destruction of a tumor suppressor protein, DLC1. By blocking the mutant RAS gene, the release of EZH2 was prevented and the activity of DLC1 was restored.

The researchers found in experiments in lung cancer cells and mouse models that combining RAS inhibitors with drugs targeted to reactivate DLC1 tumor suppressor activities had potent anti-cancer activity. It was more potent than RAS inhibitors alone.

This mechanism could be common to cancers that have mutant RAS proteins. RAS genes .

The researchers believe their findings could be useful in treating RAS-powered cancers. Researchers have begun studying how RAS works in pancreatic carcinoma, in part because this type of cancer is so difficult to treat.

Dr Lowy said new treatment combinations could be created in the future, taking into account this role of the RAS.

The National Cancer Institute: NCI leads the National Cancer Program, the NIH, and its efforts to reduce the prevalence of cancer and improve the lives of cancer patients. NCI provides extramural funding support for a variety of cancer training and research through contracts and grants. NCI’s intramural research program conducts innovative, transdisciplinary basic, translational, and clinical research, as well as epidemiologic and early detection and treatment research, at the NIH Clinic Center, the world’s largest research hospital. Learn more about NCI intramural research. Cancer Research Center. Visit the NCI website for more information about cancer. cancer.gov Call the NCI Contact Center at 1-800-422-6237 (1-800-422 6237).

The National Institutes of Health: The NIH is the medical research agency of the United States Department of Health and Human Services. It includes 27 institutes and centers. The NIH, the nation's medical research agency, is the primary federal agency that conducts and supports basic, translational, clinical, and other types of medical research. It also studies the causes, treatments, and cures of common and rare diseases. Visit the NIH for more information about its programs. www.nih.gov.

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