Heterogeneity of Colorectal Cancer Progression: Molecular Gas and Brakes.
Anticarcinogenic Agents
/ pharmacology
Biomarkers, Tumor
/ analysis
Colorectal Neoplasms
/ etiology
DNA Methylation
Drug Resistance, Neoplasm
Fusobacterium nucleatum
/ metabolism
Gastrointestinal Microbiome
High-Throughput Nucleotide Sequencing
Humans
Inflammatory Bowel Diseases
/ complications
Micronutrients
/ pharmacology
Tumor Microenvironment
/ genetics
colorectal cancer
heterogeneity
progression
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
15 May 2021
15 May 2021
Historique:
received:
22
04
2021
revised:
11
05
2021
accepted:
13
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
2
7
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34063506
pii: ijms22105246
doi: 10.3390/ijms22105246
pmc: PMC8156342
pii:
doi:
Substances chimiques
Anticarcinogenic Agents
0
Biomarkers, Tumor
0
Micronutrients
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Associazione Italiana Ricerca sul Cancro: AIRC
ID : IG 2014 Id.16092
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