Public Health & Health Science Division, ULAB

KRAS mutations are among the most common oncogenic drivers in human cancer,affecting switch control pathways that regulate cell growth, survival, and metabolism. Mutations in KRAS interfere with this regulation by keeping the protein in an active state, which causes constant signaling and is linked to cancers like pancreatic, lung, and colorectal cancer. Although significant progress has been made in developing KRAS-target therapies, many approaches focus on static protein structures and may not fully capture its dynamic behavior within living cells. This paper investigates how KRAS mutations affect signaling pathways, with a particular focuson the MAPK pathway and its role in tumor progression and therapeutic resistance. Aliterature-based methodology was used, focusing on recent peer-reviewed studies with strong mechanistic and experimental evidence, while excluding outdated or non-translational models.The analysis shows that different intervention points in the MAPK signal transduction pathway vary in their ability to shut down oncogenic signaling and prevent pathway reactivation. This question is critical because KRAS mutations drive sustained activation of the MAPK pathway,which is vital for determining whether treatments will fail due to pathway reactivation (e.g., alternative signaling routes or errors in feedback mechanisms). By understanding how targeting different points in the pathways affects both initial suppression and long-term reactivation, this paper allows for innovations and findings of new therapeutic strategies.