2023 Volume 5 Pages 16-
Colorectal cancer (CRC) remains one of the leading gastrointestinal malignancies worldwide. Development of effective therapeutics for patients diagnosed with CRC remains challenging, mainly due to innate or acquired chemoresistance arising upon treatment administration. Different mechanisms employed by CRC cells have been identified to be responsible for chemoresistance development, including mutations, cellular signalling pathways, transport-based signalling pathways and drug metabolism, among others. Additionally, biomarkers have been identified that assist in predicting treatment response, as well as providing an indication for chemoresistance development. However, the strategies and models currently used to understand this phenomenon are not enough, demanding a shift into other fields of high potential which have so far, due to technical complexity, been given less importance. This limitation is most distinct for studies related to post-translational modifications (PTMs), particularly protein methylation, and their use as predictive biomarkers for CRC chemoresistance. The development of comprehensive proteomic strategies for analysing PTMs can achieve a better understanding of potential protein methylation marks suitable as biomarker candidates for predicting treatment response in CRC. Thus, this review aims to provide a brief introduction on methodologies utilised for PTM analysis, followed by an in-depth discussion on the current strategies and models developed for analysing methyl-proteomics, together with their strengths and limitations. Lastly, this synopsis will be used to propose the future perspectives of methyl-proteomics and its involvement in predicting CRC treatment response. The identification of such biomarkers will also improve the biochemical understanding of CRC chemoresistance.