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- W4384819005 abstract "Therapeutic targeting of RAS-mutated cancers is difficult, whereas prevention or interception (treatment before or in the presence of preinvasive lesions) preclinically has proven easier. In the A/J mouse lung model, where different carcinogens induce tumors with different KRAS mutations, glucocorticoids and retinoid X receptor (RXR) agonists are effective agents in prevention and interception studies, irrespective of specific KRAS mutations. In rat azoxymethane-induced colon tumors (45% KRAS mutations), cyclooxygenase 1/2 inhibitors and difluoromethylornithine are effective in preventing or intercepting KRAS-mutated or wild-type tumors. In two KRAS-mutant pancreatic models multiple COX 1/2 inhibitors are effective. Furthermore, combining a COX and an EGFR inhibitor prevented the development of virtually all pancreatic tumors in transgenic mice. In the N-nitroso-N-methylurea-induced estrogen receptor-positive rat breast model (50% HRAS mutations) various selective estrogen receptor modulators, aromatase inhibitors, EGFR inhibitors, and RXR agonists are profoundly effective in prevention and interception of tumors with wild-type or mutant HRAS, while the farnesyltransferase inhibitor tipifarnib preferentially inhibits HRAS-mutant breast tumors. Thus, many agents not known to specifically inhibit the RAS pathway, are effective in an organ specific manner in preventing or intercepting RAS-mutated tumors. Finally, we discuss an alternative prevention and interception approach, employing vaccines to target KRAS." @default.
- W4384819005 created "2023-07-21" @default.
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- W4384819005 date "2023-07-19" @default.
- W4384819005 modified "2023-10-18" @default.
- W4384819005 title "PRIMARY PREVENTION AND INTERCEPTION STUDIES IN RAS-MUTATED TUMOR MODELS EMPLOYING SMALL MOLECULES OR VACCINES" @default.
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- W4384819005 doi "https://doi.org/10.1158/1940-6207.capr-23-0027" @default.
- W4384819005 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37468135" @default.
- W4384819005 hasPublicationYear "2023" @default.
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