Genetic and biological hallmarks of colorectal cancer

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Abstract

In this review, Li et al. detail research advances pertaining to the genetics and biology of colorectal cancer, emerging concepts gleaned from immune and single-cell profiling, and critical advances and remaining knowledge gaps influencing the development of effective therapies for this cancer.

Abstract

Colorectal cancer has served as a genetic and biological paradigm for the evolution of solid tumors, and these insights have illuminated early detection, risk stratification, prevention, and treatment principles. Employing the hallmarks of cancer framework, we provide a conceptual framework to understand how genetic alterations in colorectal cancer drive cancer cell biology properties and shape the heterotypic interactions across cells in the tumor microenvironment. This review details research advances pertaining to the genetics and biology of colorectal cancer, emerging concepts gleaned from immune and single-cell profiling, and critical advances and remaining knowledge gaps influencing the development of effective therapies for this cancer that remains a major public health burden.

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Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)

This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.

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Hallmarks of Cancer: The Next Generation

Douglas Hanahan, Robert A. Weinberg (2011)

The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

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Understanding the Warburg effect: the metabolic requirements of cell proliferation.

Craig B Thompson, Matthew Vander Heiden, Lewis Cantley (2009)

In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.

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Author and article information

Journal

Journal ID (nlm-ta): Genes Dev

Journal ID (iso-abbrev): Genes Dev

Journal ID (hwp): genesdev

Journal ID (pmc): genesdev

Journal ID (publisher-id): GAD

Title: Genes & Development

Publisher: Cold Spring Harbor Laboratory Press

ISSN (Print): 0890-9369

ISSN (Electronic): 1549-5477

Publication date (Print): June 2021

Volume: 35

Issue: 11-12

Pages: 787-820

Affiliations

Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA

Author notes

Corresponding author: rdepinho@ 123456mdanderson.org

Article

Medline ID: 8711660

DOI: 10.1101/gad.348226.120

PMC ID: 8168558

PubMed ID: 34074695

SO-VID: f045facc-ac48-4556-ae27-dbc80bc4f298

License:

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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Pages: 34

Funding

Funded by: Cancer Prevention and Research Institute of Texas , open-funder-registry 10.13039/100004917;

Funded by: Research Training Program

Award ID: RP170067

Funded by: Triumph

Funded by: CPRIT , open-funder-registry 10.13039/100004917;

Award ID: RP170067

Funded by: Digestive Disease Center-National Institute of Diabetes and Digestive and Kidney Diseases

Award ID: P30CA16672

Funded by: National Institutes of Health , open-funder-registry 10.13039/100000002;

Funded by: National Institute on Alcohol Abuse and Alcoholism , open-funder-registry 10.13039/100000027;

Award ID: U01AA027681

Funded by: NIH , open-funder-registry 10.13039/100000002;

Award ID: R01CA231360-03

Funded by: MD Anderson SPORE in Gastrointestinal Cancer

Award ID: DRP Award

Funded by: Harry Graves Burkhart III Distinguished University Chair in Cancer Research

Genetic and biological hallmarks of colorectal cancer

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Karger: Oncology

Most cited references 423

Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Hallmarks of Cancer: The Next Generation

Understanding the Warburg effect: the metabolic requirements of cell proliferation.

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