Colorectal Carcinogenesis Mechanisms and Therapeutic Approaches

Colorectal carcinogenesis arises from a multistep accumulation of genetic and epigenetic alterations that transform normal colonic epithelium into malignant lesions. Key driver events include activation of oncogenic signalling cascades—most notably the WNT/β-catenin pathway—coupled with inactivation of tumour suppressors such as APC and p53. These molecular derangements fuel unchecked proliferation, inhibit programmed cell death, and remodel the tumour microenvironment through angiogenesis and immune evasion. In parallel, chronic inflammation and dysbiosis of the gut microbiota further promote DNA damage and foster an immunosuppressive milieu. Therapeutic strategies have evolved from broad, cytotoxic chemotherapies to precision interventions targeting molecular vulnerabilities. Small-molecule inhibitors of kinases, monoclonal antibodies against growth factor receptors, and modulators of immune checkpoints have extended survival in advanced disease. Preventive approaches, including dietary modulation with bioactive compounds, aim to intercept early lesions and pre-cancerous aberrant crypt foci. Emerging modalities—such as targeted delivery of RNA therapeutics and metabolic reprogramming agents—promise to refine the balance between efficacy and tolerability. A holistic understanding of the interplay between genetic drivers, host immunity and environmental factors underpins the next generation of colorectal cancer prevention and therapy.

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Colorectal Carcinogenesis Mechanisms and Therapeutic Approaches publication trend

The graph below shows the total number of articles in colorectal carcinogenesis mechanisms and therapeutic approaches across all publications each year (not limited to Nature Index journals).

Technical terms

Aberrant crypt foci: clusters of atypical glandular structures in the colon regarded as one of the earliest precancerous lesions.

Apoptosis: programmed cell death mechanism essential for eliminating damaged or unwanted cells.

Carcinogenesis: the multistep process by which normal cells acquire malignant characteristics through genetic and epigenetic changes.

WNT/β-catenin pathway: a signalling cascade that regulates cell proliferation and differentiation; its dysregulation is central to colorectal tumour initiation.

Cell-cycle arrest: the suspension of cell-division progression, often at defined checkpoints, to repair damage or trigger apoptosis.

Xenograft: transplantation of human tumour cells into immunocompromised animals to study cancer growth and therapeutic responses.

References

1. Consumption of Feed Supplemented with Oat Beta-Glucan as a Chemopreventive Agent against Colon Cancerogenesis in Rats. Nutrients (2024).
2. Phenolic Phytochemicals for Prevention and Treatment of Colorectal Cancer: A Critical Evaluation of In Vivo Studies. Cancers (2023).
3. AGA induces sub-G1 cell cycle arrest and apoptosis in human colon cancer cells through p53-independent/p53-dependent pathway. BMC Cancer (2023).