Mount Sinai researchers have developed a therapeutic agent that shows high effectiveness in vitro at disrupting a biological pathway that helps cancer survive, according to a paper published in Cancer Discovery, a journal of the American Association for Cancer Research, in July.
The therapy is an engineered molecule, named MS21, that causes the degradation of AKT, an enzyme that is overly active in many cancers. This study laid out evidence that pharmacological degradation of AKT is a viable treatment for cancers with mutations in certain genes.
AKT is a cancer gene that encodes an enzyme that is frequently abnormally activated in cancer cells to stimulate tumor growth. Degradation of AKT reverses these processes and inhibits tumor growth.
“Our study lays a solid foundation for the clinical development of an AKT degrader for the treatment of human cancers with certain gene mutations,” said Ramon Parsons, MD, PhD, Director of The Tisch Cancer Institute and Ward-Coleman Chair in Cancer Research and Chair of Oncological Sciences at the Icahn School of Medicine at Mount Sinai. “Examination of 44,000 human cancers identified that 19 percent of tumors have at least one of these mutations, suggesting that a large population of cancer patients could benefit from therapy with an AKT degrader such as MS21.”
MS21 was tested in human cancer-derived cell lines, which are models used in laboratories to study the efficacy of cancer therapies. Mount Sinai is looking to develop MS21 with an industry partner to open clinical trials for patients.
“Translating these findings into effective cancer therapies for patients is a high priority because the mutations and the resulting cancer-driving pathways that we lay out in this study are arguably the most commonly activated pathways in human cancer, but this effort has proven to be particularly challenging,” said Jian Jin, PhD, Mount Sinai Professor in Therapeutics Discovery and Director of the Mount Sinai Center for Therapeutics Discovery at Icahn Mount Sinai. “We look forward to an opportunity to develop this molecule into a therapy that is ready to be studied in clinical trials.”
Reference: “AKT degradation selectively inhibits the growth of PI3K/PTEN pathway mutant cancers with wild-type KRAS and BRAF by destabilizing Aurora kinase B” by Jia Xu, Xufen Yu, Tiphaine C Martin, Ankita Bansal, Kakit Cheung, Abigail Lubin, Elias Stratikopoulos, Kaitlyn M Cahuzac, Li Wang, Ling Xie, Royce Zhou, Yudao Shen, Xuewei Wu, Shen Yao, Ruifang Qiao, Poulikos I Poulikakos, Xian Chen, Jing Liu, Jian Jin and Ramon Parsons, 23 July 2021, Cancer Discovery.
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The Mount Sinai Health System is New York City’s largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality care–from prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report’s “Honor Roll” of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty and our physicians in the top 1% of all physicians nationally by U.S. News & World Report.