Mechanisms of metastatic colorectal cancer

Despite extensive research and improvements in understanding colorectal cancer (CRC), its metastatic form continues to pose a substantial challenge, primarily owing to limited therapeutic options and a poor prognosis. This Review addresses the emerging focus on metastatic CRC (mCRC), which has histo...

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Bibliographic Details
Published in:Nature reviews. Gastroenterology & hepatology 2024-09, Vol.21 (9), p.609-625
Main Authors: Cañellas-Socias, Adrià, Sancho, Elena, Batlle, Eduard
Format: Article
Language:English
Subjects:
Cancer
Colorectal cancer
Colorectal carcinoma
Disease resistance
Lethality
Medical prognosis
Metastases
Metastasis
Prognosis
Tumor microenvironment
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Summary:Despite extensive research and improvements in understanding colorectal cancer (CRC), its metastatic form continues to pose a substantial challenge, primarily owing to limited therapeutic options and a poor prognosis. This Review addresses the emerging focus on metastatic CRC (mCRC), which has historically been under-studied compared with primary CRC despite its lethality. We delve into two crucial aspects: the molecular and cellular determinants facilitating CRC metastasis and the principles guiding the evolution of metastatic disease. Initially, we examine the genetic alterations integral to CRC metastasis, connecting them to clinically marked characteristics of advanced CRC. Subsequently, we scrutinize the role of cellular heterogeneity and plasticity in metastatic spread and therapy resistance. Finally, we explore how the tumour microenvironment influences metastatic disease, emphasizing the effect of stromal gene programmes and the immune context. The ongoing research in these fields holds immense importance, as its future implications are projected to revolutionize the treatment of patients with mCRC, hopefully offering a promising outlook for their survival.
ISSN:1759-5045
1759-5053
1759-5053
DOI:10.1038/s41575-024-00934-z