Dear Colleagues,

Colorectal cancer displays extensive intra-tumour and inter-tumour heterogeneity. The intra-tumour heterogeneity, as represented by so-called cancer stem cells and more differentiated progeny, has long been regarded to be a crucial factor in therapy resistance and the formation of metastases. More recent evidence indicates that cancer stemness may be a quality that cells can acquire and lose, which in part depends on the interaction with their microenvironment. Therapy resistance as well as metastatic spreading are influenced by these interactions, and more insight is needed to identify signalling nodes that could be targeted for therapy. 

Next to intra-tumour heterogeneity, there is more and more understanding of the patient-to-patient variation in colorectal cancer. Multiple subtypes have been identified, but how these different tumour types are orchestrated remains largely unknown. Whether different combinations of mutations, patient genetic background, different cells of origin, or changes in microenvironmental factors such as microbiome or lifestyle determine the phenotype of colorectal cancers remains to be established. Moreover, although a great deal of evidence exists showing that the distinct subtypes have a different clinical course and respond differently to therapeutic interventions, the exact impact on therapy remains ill-defined. In this Special Issue, experts provide new insights into colorectal cancer heterogeneity and review the current state of the art.

Prof. Dr. Jan Paul Medema
Guest Editor

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• metastatic spreading
• subtypes
• therapy resistance
• cellular wiring
• tumour microenvironment
• immune responses
• cancer stem cells