{"id":47844,"date":"2025-08-05T20:43:21","date_gmt":"2025-08-05T20:43:21","guid":{"rendered":"https:\/\/www.newsbeep.com\/ca\/47844\/"},"modified":"2025-08-05T20:43:21","modified_gmt":"2025-08-05T20:43:21","slug":"new-molecular-technology-targets-tumors-and-simultaneously-silences-two-undruggable-cancer-genes","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/ca\/47844\/","title":{"rendered":"New molecular technology targets tumors and simultaneously silences two \u2018undruggable\u2019 cancer genes"},"content":{"rendered":"

<\/p>\n

\"Chad<\/p>\n

<\/a><\/p>\n

image:\u00a0<\/p>\n

\u201cTargeting two cancer-causing genes at the same time is akin to slicing both Achilles heels of cancer, which has tremendous potential,\u201d said Chad V. Pecot, MD<\/a>, corresponding author of the article, professor of medicine at UNC School of Medicine. \u201cOur inverted molecule establishes proof-of-concept for dual-silencing of KRAS and MYC in cancer and constitutes an innovative molecular strategy for co-targeting not just those two genes, but any two genes of interest, which has broad implications.\u201d<\/p>\n

view more\u00a0<\/a><\/p>\n

Credit: UNC Lineberger Comprehensive Cancer Center<\/p>\n

CHAPEL HILL, North Carolina \u2014 University of North Carolina Lineberger Comprehensive Cancer Center researchers have developed a \u201ctwo-in-one\u201d molecule that can simultaneously turn off two notoriously difficult-to-target cancer-related genes, KRAS and MYC, as well as directly deliver drugs to tumors that express these genes. This advance holds special promise for treating cancers that have been historically challenging to treat.<\/p>\n

The new technology incorporates novel compositions of inverted RNAi molecules that have shown a marked ability to co-silence mutated KRAS and over-expressed MYC. RNA interference (RNAi) is a cellular process that uses small interfering RNAs (siRNAs) to selectively turn off, or silence, mutated genes. The co-silencing resulted in an up to a 40-fold improvement in inhibition of cancer cell viability compared to the use of individual siRNAs.<\/p>\n

The laboratory findings were published in the Journal of Clinical Investigation<\/a> on July 31.<\/p>\n

\u201cTargeting two cancer-causing genes at the same time is akin to slicing both Achilles heels of cancer, which has tremendous potential,\u201d said Chad V. Pecot, MD<\/a>, corresponding author of the article, professor of medicine at UNC School of Medicine. \u201cOur inverted molecule establishes proof-of-concept for dual-silencing of KRAS and MYC in cancer and constitutes an innovative molecular strategy for co-targeting not just those two genes, but any two genes of interest, which has broad implications.\u201d<\/p>\n

Mutated KRAS and MYC can work together to promote and maintain aggressive tumor development through several mechanisms, including stimulation of inflammation, activation of cancer cell survival pathways and suppression of cancer cell death.<\/p>\n

KRAS mutations are present in nearly 25% of all human cancers, and they frequently occur in some of the most prevalent tumor types. MYC is also regarded as a critical cancer-related gene and is dysfunctional in approximately 50-70% of cancers. Several studies have shown that inactivation of MYC can substantially inhibit tumor development, making it a very attractive therapeutic co-target.<\/p>\n

\u201cMYC seems to be nearly as important a target as KRAS, however there are still no successful drugs capable of targeting MYC,\u201d said Pecot, co-leader of the UNC Lineberger Cancer Therapeutics Program and director of the UNC RNA Discovery Center. \u201cOur study is one of the first to deeply characterize the therapeutic implications of targeting both genes at the same time. We have also made the first \u2018two-in-one\u2019 molecule capable of silencing both the KRAS and MYC proteins.\u201d<\/p>\n

Because most cancers depend on multiple genetic mutations, or drivers, for survival, this technology is especially valuable for targeting two key drivers at once. It holds particular promise when both targets, like MYC and KRAS, are critical to the cancer cell\u2019s ability to stay alive but have historically been difficult to treat with drugs. Pecot noted that the unique features of their design make it possible to begin exploring the ability to silence three targets at one time. \u201cThe opportunities are vast,\u201d he says.<\/p>\n

This discovery builds on a related finding from Pecot\u2019s lab published in Cancer Cell<\/a> in June, which described a targeted drug delivery mechanism for a specific KRAS variant known as KRAS G12V. Now, Pecot and his colleagues have developed an RNA silencing molecule capable of shutting down all KRAS mutations found in cancer.<\/p>\n

While this broader approach is less specific than the earlier KRAS G12V-targeted method, it has the potential to treat a much larger group of patients, including those with the most common KRAS mutations found in lung, colorectal, and pancreatic cancers. Together, these cancers are expected to account for nearly half a million new cases in the U.S. this year, according to the American Cancer Society.<\/p>\n

\u201cOverall, this is another nice example of RNA therapeutics being made at UNC as part of the RNA Discovery Center,\u201d Pecot said. \u201cThese advances could bring real hope to patients with KRAS-related cancers.\u201d<\/p>\n

Authors and Disclosures<\/p>\n

A complete listing of authors, funding sources and disclosures is available in the published paper.<\/p>\n

Journal<\/p>\n

Journal of Clinical Investigation<\/p>\n

Method of Research<\/p>\n

Experimental study<\/p>\n

Subject of Research<\/p>\n

Cells<\/p>\n

Article Title<\/p>\n

Inverted chimeric RNAi molecules synergistically co-target MYC and KRAS in KRAS-driven cancers<\/p>\n

Article Publication Date<\/p>\n

31-Jul-2025<\/p>\n

COI Statement<\/p>\n

Salma H. Azam, Albert A. Bowers, Yogitha S. Chareddy, Martin Egli, Matthew C. Fleming, Hayden P. Huggins, and Chad V. Pecot hold intellectual property interests based on this work (U.S. Patent No. 10,619,159, 11,180,759, 18\/571,985,34cPCT\/US2024\/034972, 17\/997,398). Pecot is founder of EnFuego Therapeutics, Inc. and holds equity in the company. Huggins and Lyla J. Stanland were employees of EnFuego Therapeutics.<\/p>\n

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.<\/p>\n","protected":false},"excerpt":{"rendered":"image:\u00a0 \u201cTargeting two cancer-causing genes at the same time is akin to slicing both Achilles heels of cancer,…\n","protected":false},"author":2,"featured_media":47845,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[25],"tags":[49,48,316,66],"class_list":["post-47844","post","type-post","status-publish","format-standard","has-post-thumbnail","category-genetics","tag-ca","tag-canada","tag-genetics","tag-science"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts\/47844","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/comments?post=47844"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts\/47844\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/media\/47845"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/media?parent=47844"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/categories?post=47844"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/tags?post=47844"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}