Colorectal cancer (CRC) is a major worldwide health problem owing to its high prevalence and mortality rates. In the USA, CRC is the third most commonly diagnosed cancer and third leading cause of cancer death in both men and women. The American Cancer Society estimates that in 2011 about 141,210 people in the USA will be diagnosed with CRC and about 49,380 people will die of the disease. It is estimated that over 40,000 of the adult UK population are diagnosed with CRC each year. If diagnosed early CRC is also one of the most curable types of cancer with cure rates as high as 90%. Evidence shows that the majority of CRCs could be prevented by applying existing knowledge of cancer prevention and by increasing the use of established screening tests.

Advances in the diagnosis and treatment of CRC have had a major impact on management of this malignancy. Developments in screening, prevention, biomarker and genomic analysis, stem-cell research, personalized therapies and chemotherapy have improved detection and mortality statistics. However, despite these advances, many patients with advanced and metastatic tumors will still succumb to the disease. Further diagnosis and treatment advances are therefore needed.

This collection of articles published in the past 18 months from Nature Reviews Clinical Oncology and Nature Reviews Gastroenterology & Hepatology comprises a selection of 9 Reviews, 3 Perspectives, 17 News & Views, and 12 Research Highlights that discuss advances in our understanding of the screening, diagnosis, prevention and treatment of this disease, as well as highlighting the challenges and future directions in this field.

A selection of original research articles and Reviews published by Nature Publishing Group journals on the topic of colorectal cancer can be found in the NPG Library.


REVIEWS

Epigenetics and colorectal cancer

Victoria Valinluck Lao & William M. Grady

doi:10.1038/nrgastro.2011.173

Nature Reviews Gastroenterology & Hepatology, advance online publication, Published online 18 October 2011

Colorectal cancer (CRC) results from an accumulation of genetic and epigenetic changes in colon epithelial cells, which transforms them into adenocarcinomas. Over the past decade, major advances have been made in understanding cancer epigenetics, particularly regarding aberrant DNA methylation. Lao and Grady provide an overview of the role of epigenetics in CRC and discuss the clinical applications of these epigenetic alterations as biomarkers for early detection, diagnosis, prognostication and management of patients with CRC.

The current landscape of locally advanced rectal cancer

Mebea Aklilu & Cathy Eng

doi:10.1038/nrclinonc.2011.118

Nature Reviews Clinical Oncology, advance online publication, Published online 9 August 2011

Current treatments for patients with locally advanced rectal cancer (LARC) consist of neoadjuvant chemoradiotherapy, followed by total mesorectal excision and adjuvant chemotherapy. Aklilu and Eng review the pivotal trials that have led to this treatment paradigm and discuss novel therapies that are being developed for patients with LARC.

Colonoscopy: basic principles and novel techniques

Yark Hazewinkel & Evelien Dekker

doi:10.1038/nrgastro.2011.141

Nature Reviews Gastroenterology & Hepatology 8, 554-564 (2011)

Colonoscopy is an endoscopic procedure that allows the entire colon to be examined, enabling both the detection and removal of premalignant lesions and colorectal tumors. Hazewinkel and Dekker provide an overview of standard colonoscopy procedures and describe the latest technical advances. They stress the importance of a minimal set of quality indicators to continuously monitor and optimize colonoscopic examinations.

Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis

Sigrun Thorsteinsdottir, Thorkell Gudjonsson, Ole Haagen Nielsen, Ben Vainer & Jakob Benedict Seidelin

doi:10.1038/nrgastro.2011.96

Nature Reviews Gastroenterology & Hepatology 8, 395-404 (2011)

The early identification of patients with ulcerative colitis who have an increased risk of colorectal cancer would be useful for clinicians. In this Review, the authors discuss the most promising preneoplastic biomarkers, including p53 mutations, chromosomal instability and senescence, in ulcerative colitis. They also present the available knowledge regarding the pathogenesis of ulcerative colitis-associated colorectal cancer.

Implementing prognostic and predictive biomarkers in CRC clinical trials

Sandra Van Schaeybroeck, Wendy L. Allen, Richard C. Turkington & Patrick G. Johnston

doi:10.1038/nrclinonc.2011.15

Nature Reviews Clinical Oncology 8, 222-232 (2011)

KRAS represents the first biomarker to be integrated in clinical practice for the treatment of colorectal cancer. However, clinical study design, reproducibility, interpretation and reporting of the clinical data remain important challenges. This Review highlights the clinical application of published prognostic and predictive protein and genomic markers and the possibilities offered by novel adaptive clinical trial designs.

Stem cells and their implications for colorectal cancer

Sebastian S. Zeki, Trevor A. Graham & Nicholas A. Wright

doi:10.1038/nrgastro.2010.211

Nature Reviews Gastroenterology & Hepatology 8, 90-100 (2011)

This Review describes the mechanisms that regulate colonic stem cell behavior and highlights how disrupting these mechanisms could drive the development of colorectal cancer. The authors focus on the colonic processes of niche succession, monoclonal conversion and field cancerization and discuss the implications and limitations of the cancer stem cell theory.

Molecular markers to individualize adjuvant therapy for colon cancer

Tara Gangadhar & Richard L. Schilsky

doi:10.1038/nrclinonc.2010.62

Nature Reviews Clinical Oncology 7, 318-325 (2010)

Prognostic and predictive markers in colon cancer might help define which patients with stage II disease are likely to benefit from adjuvant therapy. In this Review, Tara Gangadhar and Richard Schilsky discuss the recent clinical development of such markers, including microsatellite instability and 18q loss of heterozygosity. Further validation of these markers could potentially lead to the individualization of adjuvant therapy in colon cancer.

Mismatch repair deficient colorectal cancer in the era of personalized treatment

Madeleine Hewish, Christopher J. Lord, Sarah A. Martin, David Cunningham & Alan Ashworth

doi:10.1038/nrclinonc.2010.18

Nature Reviews Clinical Oncology 7, 197-208 (2010)

Mutations in the mismatch repair (MMR) genes are associated with an increased risk of developing colorectal cancer (CRC). In this Review, the authors outline the MMR system and describe how defective MMR impacts on the management of CRC. The authors also discuss how targeting these mutations can be exploited in the development of novel therapeutic strategies.

Microsatellite instability in colorectal cancer—the stable evidence

Eduardo Vilar & Stephen B. Gruber

doi:10.1038/nrclinonc.2009.237

Nature Reviews Clinical Oncology 7, 153-162 (2010)

Microsatellite instability (MSI) is a frequent molecular phenomenon of colorectal cancer and is associated with deficient DNA mismatch repair. This Review presents an overview of MSI, including its clinical features and applications. The authors discuss the prognostic and predictive value of MSI and how it can be used to improve our knowledge of other cancer subtypes.

PERSPECTIVES

Has the new TNM classification for colorectal cancer improved care?

Iris D. Nagtegaal, Phil Quirke & Hans-Joachim Schmoll

doi:10.1038/nrclinonc.2011.157

Nature Reviews Clinical Oncology, advance online publication, Published online 18 October 2011

Since the issue of the seventh edition of the TNM classification guidelines for colorectal cancer there has been discussion about some of the associated changes in classification and stage. This Perspectives article examines the impact a new staging system can have on patient care, and makes suggestions for how the constant re-evaluation of classification guidelines could be improved going forward.

Phytochemicals and colorectal cancer prevention—myth or reality?

Luigi Ricciardiello, Franco Bazzoli & Vincenzo Fogliano

doi:10.1038/nrgastro.2011.149

Nature Reviews Gastroenterology & Hepatology 8, 592-596 (2011)

Chemoprevention of colorectal cancer (CRC) has been the focus of intensive research for more than two decades. Here, Ricciardiello, Bazzoli and Fogliano discuss the association between fruit and vegetable intake and CRC risk, and the chemopreventive activities of dietary phytochemicals. They argue that a single-agent 'magic' pill for CRC chemoprevention doesn't exist and that consuming a complex mixture of phytochemicals may be the answer.

DNA mismatch repair and adjuvant chemotherapy in sporadic colon cancer

Frank A. Sinicrope

doi:10.1038/nrclinonc.2009.235

Nature Reviews Clinical Oncology 7, 174-177 (2010)

Defective DNA mismatch repair (MMR) occurs in approximately 15% of sporadic colorectal cancers. Studies have shown that patients with MMR-deficient colorectal cancers have a more favorable prognosis, but evidence indicates these patients do not benefit from adjuvant 5 fluorouracil-based chemotherapy. The importance of determining MMR status to inform clinical decision-making for adjuvant chemotherapy in patients with stage II colon cancer is discussed.

NEWS & VIEWS

Colorectal cancer: Increasing colorectal cancer screening—miles to go

Audrey H. Calderwood & Paul C. Schroy 3rd

doi:10.1038/nrgastro.2011.123

Nature Reviews Gastroenterology & Hepatology 8, 421-422 (2011)

Targeted therapies: Bevacizumab—has it reached its final resting place?

David J. Kerr & Annie M. Young

doi:10.1038/nrclinonc.2011.32

Nature Reviews Clinical Oncology 8, 195-196 (2011)

Cancer: Lynch syndrome—how should colorectal cancer be managed?

Hans F. A. Vasen & Wouter H. de Vos tot Nederveen Cappel

doi:10.1038/nrgastro.2011.34

Nature Reviews Gastroenterology & Hepatology 8, 184-186 (2011)

Colorectal cancer: Managing diminutive polyps—what is the optimal approach?

David H. Kim & Perry J. Pickhardt

doi:10.1038/nrgastro.2011.19

Nature Reviews Gastroenterology & Hepatology 8, 129-131 (2011)

Cancer: Do aspirin and other NSAIDs protect against colorectal cancer?

Sarah Kraus & Nadir Arber

doi:10.1038/nrgastro.2010.217

Nature Reviews Gastroenterology and Hepatology 8, 125-126 (2011)

Prevention: Will an aspirin a day keep the colorectal cancer away?

Marianne Berg & Kjetil Søreide

doi:10.1038/nrclinonc.2010.225

Nature Reviews Clinical Oncology 8, 130-131 (2011)

Genetics: An 18-gene signature (ColoPrint®) for colon cancer prognosis

Iain B. Tan & Patrick Tan

doi:10.1038/nrclinonc.2010.229

Nature Reviews Clinical Oncology 8, 131-133 (2011)

Chemotherapy: Failure of bevacizumab in early-stage colon cancer

Daniel J. Sargent

doi:10.1038/nrclinonc.2010.205

Nature Reviews Clinical Oncology 8, 10-11 (2011)

Risk factors: Hyperplastic polyposis syndrome and risk of colorectal cancer

Joanne P. Young & Susan Parry

doi:10.1038/nrgastro.2010.166

Nature Reviews Gastroenterology & Hepatology 7, 594-595 (2010)

Medical oncology: A novel low-toxicity regimen for advanced colorectal cancer?

Yoko Yanagisawa & Rachel S. Midgley

doi:10.1038/nrclinonc.2010.140

Nature Reviews Clinical Oncology 7, 556-557 (2010)

Screening: Flexible sigmoidoscopy—valuable in colorectal cancer

Eliza A. Hawkes & David Cunningham

doi:10.1038/nrclinonc.2010.102

Nature Reviews Clinical Oncology 7, 488-490 (2010)

Screening: Endomicroscopy for a reliable diagnosis of colorectal neoplasia

Ralf Kiesslich

doi:10.1038/nrgastro.2010.113

Nature Reviews Gastroenterology & Hepatology 7, 422-423 (2010)

Screening: Screening flexible sigmoidoscopy effective in a UK RCT

Douglas K. Rex

doi:10.1038/nrgastro.2010.111

Nature Reviews Gastroenterology & Hepatology 7, 423-424 (2010)

Cancer: What is the best screening test for colorectal cancer?

Jean Faivre

doi:10.1038/nrgastro.2010.49

Nature Reviews Gastroenterology & Hepatology 7, 245-246 (2010)

Cancer: Subsite differences in colorectal cancer—anything new?

John D. Potter

doi:10.1038/nrgastro.2010.48

Nature Reviews Gastroenterology & Hepatology 7, 248-249 (2010)

Chemotherapy: How useful is adjuvant irinotecan in stage IV CRC?

Fotios Loupakis & Alfredo Falcone

doi:10.1038/nrclinonc.2010.32

Nature Reviews Clinical Oncology 7, 190-191 (2010)

Radiotherapy: Preoperative chemoradiotherapy for rectal cancer

Claus Rödel

doi:10.1038/nrclinonc.2010.10

Nature Reviews Clinical Oncology 7, 129-130 (2010)

RESEARCH HIGHLIGHTS

Colorectal cancer: Telomere length and risk of CRC

Isobel Franks

doi:10.1038/nrgastro.2011.136

Nature Reviews Gastroenterology & Hepatology 8, 475 (2011)

Surgery: Colonic stenting no better than emergency surgery?

Rebecca Kirk

doi:10.1038/nrclinonc.2011.57

Nature Reviews Clinical Oncology 8, 318 (2011)

Cancer: HDL cholesterol and cancer risk

Claire Greenhill

doi:10.1038/nrgastro.2011.52

Nature Reviews Gastroenterology & Hepatology 8, 299 (2011)

Targeted therapies: Dasatinib sensitizes KRAS-mutant colorectal cancer tumors to cetuximab

Lisa Hutchinson

doi:10.1038/nrclinonc.2011.24

Nature Reviews Clinical Oncology 8, 193 (2011)

Genetics: In colorectal cancer, not all KRAS mutations are created equal

Rebecca Kirk

doi:10.1038/nrclinonc.2010.204

Nature Reviews Clinical Oncology 8, 1 (2011)

Targeted therapies: Panitumumab improves PFS in mCRC with wild-type KRAS

Lisa Hutchinson

doi:10.1038/nrclinonc.2010.176

Nature Reviews Clinical Oncology 7, 672 (2010)

Cancer: New biomarkers of good prognosis in colorectal cancer identified

Claire Greenhill

doi:10.1038/nrgastro.2010.124

Nature Reviews Gastroenterology & Hepatology 7, 475 (2010)

Therapy: EPA—a new therapy for familial adenomatous polyposis?

Katrina Ray

doi:10.1038/nrgastro.2010.108

Nature Reviews Gastroenterology & Hepatology 7, 416 (2010)

Risk factors: CD8+:FOXP3+ cell ratio is a novel survival marker for colorectal cancer

Rebecca Kirk

doi:10.1038/nrclinonc.2010.79

Nature Reviews Clinical Oncology 7, 299 (2010)

Screening: A re-evaluation of KRAS mutational 'hotspots'

Rowan Higgs

doi:10.1038/nrclinonc.2010.54

Nature Reviews Clinical Oncology 7, 242 (2010)

Genetics: BRAF but not KRAS is prognostic in colon cancer

Lisa Hutchinson

doi:10.1038/nrclinonc.2010.25

Nature Reviews Clinical Oncology 7, 184 (2010)

New prognostic markers for CRC

Katrina Ray

doi:10.1038/nrclinonc.2010.29

Nature Reviews Clinical Oncology 7, 182 (2010)

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