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Review
. 2021 May 15;22(10):5246.
doi: 10.3390/ijms22105246.

Heterogeneity of Colorectal Cancer Progression: Molecular Gas and Brakes

Federica Gaiani  1   2 , Federica Marchesi  3   4 , Francesca Negri  5 , Luana Greco  6 , Alberto Malesci  3   7 , Gian Luigi de'Angelis  1   2 , Luigi Laghi  1   6
Affiliations
Review

Heterogeneity of Colorectal Cancer Progression: Molecular Gas and Brakes

Federica Gaiani et al. Int J Mol Sci. .

Abstract

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.

Keywords: colorectal cancer; heterogeneity; progression.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scheme of the cancer immune cycle, depicting antigen-presenting cells (mostly dendritic cells, DC), which infiltrate the tumor tissue, uptake tumor-derived products and traffic to draining lymph nodes, therein presenting antigens to antigen-specific cytotoxic T cells. Sustained immunosuppressive circuits may induce T-cell dysfunction, immune escape and eventually cancer progression.
Figure 2
Figure 2
Prognostic subgroups within stage III colon cancers by therapeutic options: surgery alone; fluoropyrimidine alone; oxaliplatin-based doublet for 3 months; oxaliplatin-based doublet for 6 months.
Figure 3
Figure 3
Principles of temporal and spatial heterogeneity of cancer.
See this image and copyright information in PMC

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