Abstract
Colorectal cancer (CRC) is one of the most common cancer types and represents a major therapeutic challenge. Although initial events in colorectal carcinogenesis are relatively well characterized and treatment for early‐stage disease has significantly improved over the last decades, the mechanisms underlying metastasis – the main cause of death – remain poorly understood. Correspondingly, no effective therapy is currently available for advanced or metastatic disease. There is increasing evidence that colorectal cancer is hierarchically organized and sustained by cancer stem cells, in concert with various stromal cell types. Here, we review the interplay between cancer stem cells and their microenvironment in promoting metastasis and discuss recent insights relating to both patient prognosis and novel targeted treatment strategies. A better understanding of these topics may aid the prevention or reduction of metastatic burden.
Highlights
Colorectal cancer (CRC) is one of the most frequent types of cancer worldwide, accounting for approximately10% of all new cancer cases and 8.5% of all cancer deaths (Torre et al, 2015)
We review the interplay between cancer stem cells and their microenvironment in promoting metastasis and discuss recent insights relating to both patient prognosis and novel targeted treatment strategies
TGF-beta activates a wide range of tumour stroma cell types (Pickup et al, 2013), cancer-associated fibroblast (CAF) are the main contributors to the association of stromal TGF-beta-driven programmes with poor clinical outcome in CRC, suggesting a predominant role of TGF-beta-activated CAFs during progression to metastasis (Calon et al, 2015)
Summary
Colorectal cancer (CRC) is one of the most frequent types of cancer worldwide, accounting for approximately. In the absence of mutations that associate with the process of metastasis in CRC, it has become increasingly clear that the regeneration of the tumour in a foreign organ is tightly bound to the acquisition of a stemlike phenotype by cancer cells These metastatic stem cells adopt multiple phenotypes and behaviours and critically depend on their interaction with the microenvironment to migrate, survive in the circulation and thrive in a foreign organ. This includes a dissection of the cell types and niches that support the survival and maintenance of metastatic stem cells, and an analysis of the ways that stromal features can improve disease prognosis. We will indicate how these emerging concepts are informing, and slowly transforming, therapeutic strategies to treat patients with metastatic disease
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