Gaiani Federica, Marchesi Federica, Negri Francesca, Greco Luana, Malesci Alberto, de'Angelis Gian Luigi, Laghi Luigi
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
Gastroenterology and Endoscopy Unit, University-Hospital of Parma, via Gramsci 14, 43126 Parma, Italy.
Int J Mol Sci. 2021 May 15;22(10):5246. doi: 10.3390/ijms22105246.
The review begins with molecular genetics, which hit the field unveiling the involvement of oncogenes and tumor suppressor genes in the pathogenesis of colorectal cancer (CRC) and uncovering genetic predispositions. Then the notion of molecular phenotypes with different clinical behaviors was introduced and translated in the clinical arena, paving the way to next-generation sequencing that captured previously unrecognized heterogeneity. Among other molecular regulators of CRC progression, the extent of host immune response within the tumor micro-environment has a critical position. Translational sciences deeply investigated the field, accelerating the pace toward clinical transition, due to its strong association with outcomes. While the perturbation of gut homeostasis occurring in inflammatory bowel diseases can fuel carcinogenesis, micronutrients like vitamin D and calcium can act as brakes, and we discuss underlying molecular mechanisms. Among the components of gut microbiota, Fusobacterium nucleatum is over-represented in CRC, and may worsen patient outcome. However, any translational knowledge tracing the multifaceted evolution of CRC should be interpreted according to the prognostic and predictive frame of the TNM-staging system in a perspective of clinical actionability. Eventually, we examine challenges and promises of pharmacological interventions aimed to restrain disease progression at different disease stages.
本综述始于分子遗传学，该领域揭示了癌基因和肿瘤抑制基因在结直肠癌（CRC）发病机制中的作用，并发现了遗传易感性。随后，具有不同临床行为的分子表型概念被引入并应用于临床领域，为捕捉先前未被认识的异质性的下一代测序铺平了道路。在CRC进展的其他分子调节因子中，肿瘤微环境中宿主免疫反应的程度具有关键地位。转化科学对该领域进行了深入研究，由于其与预后密切相关，加快了向临床转化的步伐。虽然炎症性肠病中发生的肠道稳态紊乱可促进癌变，但维生素D和钙等微量营养素可起到抑制作用，我们将讨论其潜在的分子机制。在肠道微生物群的组成成分中，具核梭杆菌在CRC中过度存在，可能会使患者预后恶化。然而，任何追踪CRC多方面演变的转化知识都应根据TNM分期系统的预后和预测框架，从临床可操作性的角度进行解读。最后，我们探讨了旨在抑制不同疾病阶段疾病进展的药物干预措施所面临的挑战和前景。
