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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\u2019s intrinsic and extrinsic drivers, including genetic, metabolic, and dietary influences, is essential for developing personalized treatment strategies and improving patient outcomes.<\/jats:p>","DOI":"10.3390\/ijms27104299","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T16:04:36Z","timestamp":1778601876000},"page":"4299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inflammation and Colorectal Cancer Pathogenesis: Molecular, Immunological, and Environmental Features for Therapy Response and Resistances"],"prefix":"10.3390","volume":"27","author":[{"given":"Barbara","family":"Seliger","sequence":"first","affiliation":[{"name":"Institute of Translational Immunology, Brandenburg Medical School \u201cTheodor Fontane\u201d, 14770 Brandenburg an der Havel, Germany"},{"name":"Faculty of Health Sciences Brandenburg, Brandenburg 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soeren","family":"Ocvirk","sequence":"additional","affiliation":[{"name":"Gnotobiology Research Unit, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany"},{"name":"Research Group WESTGUT, ZIEL, Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4495-1724","authenticated-orcid":false,"given":"Janine","family":"Kah","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Brandenburg, Brandenburg Medical School \u201cTheodor Fontane\u201d, 14770 Brandenburg an der Havel, Germany"},{"name":"Centre for Translational Medicine, Brandenburg Medical School \u201cTheodor Fontane\u201d, 14770 Brandenburg an der Havel, Germany"},{"name":"Department of Gastroenterology, University Hospital Brandenburg, Brandenburg Medical School \u201cTheodor Fontane\u201d, 14770 Brandenburg an der Havel, Germany"},{"name":"Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kalinski","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospital Brandenburg, Brandenburg Medical School \u201cTheodor Fontane\u201d, 14770 Brandenburg an der Havel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Massa","sequence":"additional","affiliation":[{"name":"Institute of Translational Immunology, Brandenburg Medical School \u201cTheodor Fontane\u201d, 14770 Brandenburg an der Havel, Germany"},{"name":"Faculty of Health Sciences Brandenburg, Brandenburg Medical School \u201cTheodor Fontane\u201d, 14770 Brandenburg an der Havel, Germany"},{"name":"Centre for Translational Medicine, Brandenburg Medical School \u201cTheodor Fontane\u201d, 14770 Brandenburg an der 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