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Combined EZH2 and RAS pathway inhibitors kill KRAS-mutant colorectal cancer cells and promote durable tumor regression in vivo. These agents function by cooperatively suppressing the WNT pathway, driving differentiation, and epigenetically reprogramming cells to permit the induction of apoptotic signals, which then kill these more differentiated tumor cells.
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http://dx.doi.org/10.1158/2159-8290.CD-23-0866 | DOI Listing |
Cancer Discov
December 2024
Genetics Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Combined EZH2 and RAS pathway inhibitors kill KRAS-mutant colorectal cancer cells and promote durable tumor regression in vivo. These agents function by cooperatively suppressing the WNT pathway, driving differentiation, and epigenetically reprogramming cells to permit the induction of apoptotic signals, which then kill these more differentiated tumor cells.
View Article and Find Full Text PDFUnlabelled: Myristoylation is a type of protein acylation by which the fatty acid myristate is added to the N-terminus of target proteins, a process mediated by N-myristoyltransferases (NMT). Myristoylation is emerging as a promising cancer therapeutic target; however, the molecular determinants of sensitivity to NMT inhibition or the mechanism by which it induces cancer cell death are not completely understood. We report that NMTs are a novel therapeutic target in lung carcinoma cells with LKB1 and/or KEAP1 mutations in a KRAS-mutant background.
View Article and Find Full Text PDFTherap Adv Gastroenterol
May 2024
Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangzhou 510655, China.
Biomed Res Int
January 2023
National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan.
Background: Kirsten rat sarcoma (KRAS) protein is an essential contributor to the development of pancreatic ductal adenocarcinoma (PDAC). KRAS G12D and G12V mutant tumours are significant challenges in cancer therapy due to high resistance to the treatment.
Objective: To determine how effective is the ATO/D-VC combination in suppression of PDAC the mouse transgenic model.
Cancer Biol Med
August 2021
Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
Objective: Mutant KRAS, the principal isoform of RAS, plays a pivotal role in the oncogenesis of colorectal cancer by constitutively activating the RAF/MEK/ERK and PI3K/AKT pathways. Effective targeted therapies are urgently needed. We investigated whether rigosertib, a benzyl styryl sulfone RAS signaling disruptor, could selectively kill -mutant colorectal cancer cells.
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