study<\/a>, University of Michigan researchers have identified a new target that can suppress tumor growth.<\/p>\nTheir findings may lead to new treatment methods for GEP-NETs.<\/p>\n
The typical treatment for GEP-NETs involves targeting mTOR, which controls protein and lipid synthesis.<\/p>\n
Inhibiting mTOR, through the medication everolimus, slows down tumor growth but does not kill the cells.<\/p>\n
Therefore, patients respond to treatment only for a short period of time before developing resistance.<\/p>\n
In the present study, the team screened for cell pathways that can target GEP-NETs.<\/p>\n
They found that PIKfyve, a therapeutic target in prostate, pancreatic and breast cancer, is also important in GEP-NETs.<\/p>\n
\u201cPIKfyve was present in higher levels in GEP-NETs compared to the normal surrounding tissues,\u201d said Yuanyuan Qiao, Ph.D., Research Assistant Professor of Translational Pathology.<\/p>\n
\u201cThat suggested PIKfyve has a role in either promoting GEP-NET survival or growth.\u201d<\/p>\n
Using tumor models, the researchers confirmed that inhibiting PIKfyve reduced tumor volume and weight compared to the control.<\/p>\n
They found that PIKfyve controls the cell\u2019s \u2018cleanup\u2019 process, called autophagy, where cellular components are recycled to help cells survive.<\/p>\n
As a result, PIKfyve also influenced lipid synthesis, but through a different pathway when compared to mTOR.<\/p>\n
The researchers found that when both PIKfyve and mTOR were targeted in pancreatic neuroendocrine tumor models, the mice had fewer tumors and survived longer compared to the controls or targeting only one of the pathways.<\/p>\n
Although PIKfyve has been identified as a target in other tumors, there are no FDA-approved PIKfyve inhibitors.<\/p>\n
The researchers are hoping that ESK981, a PIKfyve inhibitor that is currently being as a phase 2 drug in the Rogel Cancer Center, can eventually be used in combination with mTOR inhibitors.<\/p>\n
\u201cBy co-targeting these complementary mechanisms, we can transform a largely growth-suppressive therapy into one that more effectively drives tumor cell death, offering a promising new strategy to overcome treatment resistance,\u201d said Arul Chinnaiyan, M.D., Ph.D., S. P. Hicks Endowed Professor of Pathology.<\/p>\n
\u201cThe next step, of course, will be to evaluate this approach in patients with gastroenteropancreatic neuroendocrine tumors.”<\/p>\n
Additional authors:\u00a0Yizhi Cao, Caleb Cheng, Yitong Yin, Sarah N. Yee, Yang Zheng, Somnath Mahapatra, Radha Paturu, Andrej Coleski, Shannon VanAken, Fan Yang, R\u00fcya Pakkan, Yi Zhao, Rupam Bhattacharyya, Stephanie J. Miner, Xuhong Cao, Rahul Mannan, Chungen Li, Vaibhav Sahai, Ke Ding and Costas A. Lyssiotis.<\/p>\n
Funding\/disclosures:\u00a0This work was supported by the National Cancer Institute Outstanding Investigator Award R35-CA231996, Department of Defense Idea Development Award HT9425-23-1-0084, the Neuroendocrine Tumor Research Foundation Investigator Award, the NCI (R37-CA237421, R01-CA248160, R01-CA244931), an NCI F30 fellowship (F30CA288093) and NIH T32 training grants (CMB:5T32-GM145470, MSTP: T32GM00786). Chinnaiyan is a Howard Hughes Medical Institute Investigator, A. Alfred Taubman Scholar, and American Cancer Society Professor.<\/p>\n
Tech transfer(s)\/Conflict(s) of interest:\u00a0Chinnaiyan is a co-founder and serves on the Scientific Advisory Board of Esanik Therapeutics, Inc., which owns proprietary rights to the clinical development of ESK981. He is a co-founder and serves on the SAB of Medsyn Bio, Lynx Dx and NuLynx Therapeutics and serves as an advisor to Tempus AI, Proteovant, Aurigene Oncology, and Ascentage Pharmaceuticals. Chinnaiyan, Qiao, Lyssiotis, Cheng, Ding and Li are listed as inventors on the following patents pertaining to development of methodologies and compounds targeting PIKfyve in diseases: PCT: PCT\/US2021\/057022; PCT: PCT\/US2024\/017088; PCT: PCT\/CN2024\/087809, US Patent No: 63\/537,996, US Patent No: 63\/841,641, US Patent No: PCT\/CN2024\/078381<\/p>\n
Paper cited:\u00a0\u201cTargeting the Ferritinophagy-Lysosome Axis as a Therapeutic Vulnerability in Gastroenteropancreatic Neuroendocrine Tumors,\u201d\u00a0Cell Reports Medicine.\u00a0DOI: 10.1016\/j.xcrm.2026.102695<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"Newswise \u2014 Neuroendocrine cells are unique in their ability to act both as nerve cells and hormone-making cells.…\n","protected":false},"author":2,"featured_media":384823,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[1382,8845,171326,103,396,61,60,171327,21258,1378,76957],"class_list":{"0":"post-384822","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-cell-biology","9":"tag-clinical-trials","10":"tag-gastroenteropancreatic-neuroendocrine-tumorsneuroendocrine-tumorsmtor-inhibitors","11":"tag-health","12":"tag-healthcare","13":"tag-ie","14":"tag-ireland","15":"tag-michigan-medicine-university-of-michigan","16":"tag-neuro","17":"tag-newswise","18":"tag-patient-safety"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/384822","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=384822"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/384822\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/384823"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=384822"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=384822"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=384822"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}