Inflammation and colorectal cancer pathogenesis: Molecular, immunological, and environmental features for therapy response and resistances

Colorectal cancer (CRC) is a significant global health concern, ranking as the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths. Advances in screening, such as the implementation of liquid biopsies (LB), have improved early detection, thus enhancing survival rates. This review summarizes the multifaceted nature of CRC, focusing on its genetic background, the complex tumor microenvironment, and the influence of gut microbiota, nutrition, and metabolic alterations. The development of CRC is influenced by various risk factors, including age, genetics, chronic diseases, and lifestyle choices. The genetic heterogeneity of CRC defines distinct molecular subtypes, characterized by different treatment responses and patient prognoses. Chronic inflammation and dysbiosis in the gut microbiota further contribute to CRC pathogenesis. In addition, nutritional factors play a crucial role in CRC, affecting carcinogenesis and treatment efficacy through direct interaction with the immune system and microbiome. Current therapeutic strategies include surgical interventions, chemo- and radiotherapy, targeted therapies, immunotherapy as well as dietary interventions, and microbiome modulation, highlighting the challenges posed by tumor heterogeneity and treatment resistance. In sum, a comprehensive understanding of CRC’s intrinsic and extrinsic drivers, including genetic, metabolic, and dietary influences, is essential for developing personalized treatment strategies and improving patient outcomes.