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image of Innovative Therapies for Oncogenic KRAS Mutations: Precision Strategies with PROTACs in Cancer Treatment

Abstract

The KRAS (Kirsten rat sarcoma viral oncogene homolog) gene mutation is commonly found in colorectal, lung, and pancreatic carcinomas. Unfortunately, blocking KRAS straight away has proven to be challenging. PROTACs (Proteolysis Targeting Chimeras), a class of bifunctional molecules, are designed to break down proteins, offering a unique strategy to target KRAS and overcome the limitations of traditional inhibition. This review discusses PROTACs targeting KRAS mutations in cancer, highlighting major findings, current limitations, and future perspectives. The review was performed using the databases, namely, Medline, Embase, Science Direct, and Scopus, using the keywords “PROTACs, protein degradation, anti-tumor action, cancer treatment, KRAS mutation”. Additional information was gathered from related textbooks, reviews, and documents. PROTAC treatment results in the suppression of downstream signalling pathways associated with KRAS, such as the MAPK and PI3K/AKT pathways. Animal studies demonstrate the ability of the PROTAC to effectively target KRAS-mutant tumors, inhibiting tumour growth without significant toxicities. New advances in this field can lead to cancer treatments that specifically target KRAS-mutant tumors.

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2025-06-04
2025-09-26

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/content/journals/acamc/10.2174/0118715206377691250523095407
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Innovative Therapies for Oncogenic KRAS Mutations: Precision Strategies with PROTACs in Cancer Treatment
Bentham Science Publishers ; https://doi.org/10.2174/0118715206377691250523095407
/content/journals/acamc/10.2174/0118715206377691250523095407
/content/journals/acamc/10.2174/0118715206377691250523095407
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  • Article Type:     Review Article
Keywords: cancer treatment ; KRAS mutation ; PROTACs ; protein degradation ; anti-tumor action ; animal studies

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