Table 1_Senescence-associated and immune-related 9p21.3 locus genes in colorectal cancer: epigenetic architecture, molecular landscape and therapeutic possibilities.xlsx

Colorectal cancer (CRC) progression is influenced by genetic and epigenetic aberrations. Oncogenesis of CRC involves the accumulation of mutations in proteins involved in the regulation of cell proliferation, growth and death (Graphical abstract A). DNA methylation has been demonstrated to contribute to tumor initiation, progression, and modulation of therapeutic responses. In this particular landscape, the 9p21.3 locus has been observed to integrate various cellular processes, including cell cycle control (CDKN2A/CDKN2B and ANRIL), immune signaling (cluster of type I interferons), and metabolic regulation (MTAP, MLLT3). This creates relationships that may affect tumor intrinsic and extrinsic features, immunogenicity, and therapeutic sensitivity. The objective of our analysis is to provide a comprehensive overview of the role of the 9p21.3 locus in CRC, focusing on its potential implications for treatment decisions and prediction of treatment responses. Analyzing the 9p21.3 status would help stratify CRC patients into different groups and guide the choice of personalized therapy for CRC. It could also enhance current CRC treatment by pretreating patients with demethylating agents and using an immunotherapeutic approach in combination with senolytic drugs (Graphical abstract B).