Abstract
With the advent of Kirsten rat sarcoma viral oncogene homologue G12C (KRAS G12C) inhibitors, RAS is no longer considered undruggable. For the suppression of RAS, new therapeutic approaches have been suggested. However, current clinical studies have indicated therapeutic resistance after short-lived tumour suppression. According to preclinical studies, this might be associated with acquired genetic alterations, reactivation of downstream pathways, and stimulation for upstream signalling. In this review, we aimed to summarize current approaches for combination therapy to alleviate resistance to KRAS G12C inhibitors in colorectal cancer with a focus on the mechanisms of therapeutic resistance. We also analysed the relationship between various mechanisms and therapeutic resistance.