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

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. To achieve this, we thoroughly analyzed literature sourced from reputable databases, including PubMed, Google Scholar, and ScienceDirect. Various relevant articles were obtained from the reference section of the selected papers. PROTACs successfully induce the degradation of mutant KRAS in cell lines, leading to a decrease in cell viability compared to control groups. 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.