From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies

Sep 21, 2026

Uploaded by Miles

Colorectal cancer (CRC) represents a major global health burden, characterized by high incidence and mortality worldwide. This review synthesizes current knowledge on CRC epidemiology, risk factors, and molecular pathogenesis, emphasizing clinical and molecular distinctions between colon and rectal cancers and the influence of tumor location on treatment. It details multistep carcinogenesis pathways, including adenoma–carcinoma progression, serrated routes, and the Vogelstein model, and examines consensus molecular subtypes (CMS1–CMS4) to inform disease heterogeneity and personalized therapy. The article also describes colonic crypt cellular architecture and its role in intestinal homeostasis.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages124

Reading Time5 h 12 min

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Introduction

Colorectal Cancer around the World: Burden, Risks, and Management

Review From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies Ehsan Gharib 1,2, * and Gilles A. Robichaud 1,2, * Citation: Gharib, E.; Robichaud, G.A. From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies. Int. J. Mol. Sci. 2024, 25, 9463. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms25179463 Academic Editor: Takuji Tanaka Received: 29 July 2024 Revised: 19 August 2024 Accepted: 24 August 2024 Published: 30 August 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 D²partement de Chimie et Biochimie, Universit² de Moncton, Moncton, NB E1A 3E9, Canada 2 Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada * Correspondence: [ehsangharib55@gmail.com or ehsan.gharib@umoncton.ca](ehsangharib55@gmail.com or ehsan.gharib@umoncton.ca) (E.G.); [gilles.robichaud@umoncton.ca](gilles.robichaud@umoncton.ca) (G.A.R.); Tel.: +1-506-688-3899 (E.G.); +1-506-858-4320 (G.A.R.) Abstract: Colorectal cancer (CRC) represents a signiﬁcant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies. We also present the intricate cellular architecture of colonic crypts and their roles in intestinal homeostasis. Colorectal carcinogenesis multistep processes are also described, covering the conventional adenoma– carcinoma sequence, alternative serrated pathways, and the inﬂuential Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. The consensus molecular CRC subtypes (CMS1-CMS4) are examined, shedding light on disease heterogeneity and personalized therapy implications. Keywords: colorectal cancer; epidemiology; molecular pathogenesis; risk factor; therapeutic strategy 1. Introduction Over the past decade, signiﬁcant advances have been made to our understanding of cellular and molecular processes supporting CRC pathogenesis. This has been largely due to experimental animal models, patient-derived resources, and advanced techniques (i.e., organoids/xenografts) . These advances have provided invaluable contributions to decipher intratumoral heterogeneity and cancer subtype nomenclature. Globally, this knowledge has paved the way to current screening, prevention programs, and intervention (i.e., surgical, chemotherapeutic, and emerging targeted/immunotherapy) management strategies. The following Sections of this review will encompass current knowledge on CRC biology, pathogenesis, and mechanistic networks while emphasizing strategic approaches and ongoing research for improving patient outcome and personalized therapy. 1.1. Colorectal Cancer around the World: Burden, Risks, and Management Colorectal cancer (CRC) poses a major global health challenge [1] . It is one of the most commonly diagnosed cancers worldwide and a leading cause of cancer-related mortality internationally [1,2] . In 2022, CRC accounted for over 1.9 million new cases and 904,019 deaths globally according to estimates from the Global Cancer Observatory (GLOBOCAN) [3] . As shown in Table 1, the incidence and mortality rates vary substantially between world regions where developed nations report higher CRC burden [3] . Various lifestyle and hereditary risk factors inﬂuence CRC development [4–11] . Age is the pr

FAQs

What key clinical and molecular differences influence CRC treatment approaches?

The review highlights distinct clinical and molecular characteristics between colon and rectal cancers, underscoring how tumor location can affect treatment strategy.

Which carcinogenesis pathways are discussed for colorectal cancer development?

It covers multistep processes including the conventional adenoma–carcinoma sequence, alternative serrated pathways, and the Vogelstein model with sequential APC, KRAS, and TP53 alterations.

How do consensus molecular CRC subtypes support personalized therapy?

The article examines CMS1–CMS4 to illustrate CRC heterogeneity and to clarify implications for tailored therapeutic decision-making.

Sep 21, 2026

Uploaded by Miles

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