Colorectal Adenomas

Kelloff, Gary J.; Schilsky, Richard L.; Alberts, David S.; Day, Robert W.; Guyton, Kathryn Z.; Pearce, Homer L.; Peck, Jonathan; Phillips, Robert; Sigman, Caroline C.

doi:10.1158/1078-0432.ccr-03-0789

Cited by 64 publications

(34 citation statements)

References 113 publications

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“…Combining epidemiologic leads with experimental data provides a rationale for use of these targets in chemoprevention. For example, numerous studies associate lower incidence of colon cancers, colorectal adenomas, and colorectal cancer mortality with use of aspirin and NSAIDs (86,99). These data led to the exploration of COX inhibition, the primary mechanistic activity of these drugs, for Fig.…”

Section: Epidemiologic and Experimental Evidencementioning

confidence: 99%

“…Carcinogenesis is driven by genetic progression.This progression is marked by the appearance of molecular biomarkers in distinctive patterns representing accumulating changes in gene expression and correlating with changes in histologic phenotype as cells move from normal through the very early stages of precancer, through more severe precancer, to early cancer and finally through early invasive, locally advanced, and metastatic cancer. The figure shows candidate molecular biomarkers of genetic progression in seven target organs: prostate (133,408,409), colon (16,99), breast (1,410), lung (260^262), head and neck (292^294, 299), esophagus (320,326,329), and liver (351). In most tissues, the earliest biomarkers are changes in expression of tumor suppressors and oncogenes, with biomarkers associated with proliferation and uncontrolled growth (e.g., cyclin D1) and invasion usually emerging later.…”

Section: Prostate Cancermentioning

confidence: 99%

“…Most sporadic colorectal cancers are believed to develop from a precursor IEN, sporadic adenomas (86,99). The adenomato-carcinoma sequence describes the common pathway taken by neoplasms that arise as the result of the progressive accumulation of genetic changes, which may include alterations in protooncogenes, loss of tumor suppressor gene activity, and abnormalities in genes involved in DNA repair.…”

Section: Colorectal Cancermentioning

confidence: 99%

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Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer—A Plan to Move Forward

Kelloff

Lippman

Dannenberg

et al. 2006

Clinical Cancer Research

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253

196

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This article reviews progress in chemopreventive drug development, especially data and concepts that are new since the 2002 AACR report on treatment and prevention of intraepithelial neoplasia. Molecular biomarker expressions involved in mechanisms of carcinogenesis and genetic progression models of intraepithelial neoplasia are discussed and analyzed for how they can inform mechanism-based, molecularly targeted drug development as well as risk stratification, cohort selection, and end-point selection for clinical trials.We outline the concept of augmenting the risk, mechanistic, and disease data from histopathologic intraepithelial neoplasia assessments with molecular biomarker data. Updates of work in 10 clinical target organ sites include new data on molecular progression, significant completed trials, new agents of interest, and promising directions for future clinical studies. This overview concludes with strategies for accelerating chemopreventive drug development, such as integrating the best science into chemopreventive strategies and regulatory policy, providing incentives for industry to accelerate preventive drugs, fostering multisector cooperation in sharing clinical samples and data, and creating public-private partnerships to foster new regulatory policies and public education.In most epithelial tissues, accumulating mutations (i.e., genetic progression) and loss of cellular control functions cause progressive phenotypic changes from normal histology to early precancer [intraepithelial neoplasia (IEN)] to increasingly severe IEN to superficial cancer and finally to invasive disease. This process can be relatively aggressive in some settings (e.g., in the presence of a DNA repair -deficient genotype) but generally occurs relatively slowly over years and decades. Cancer chemoprevention can be defined as the prevention of cancer or treatment of identifiable precancers (defined as histopathologic or molecular IEN). The long latency to invasive cancer is a major scientific opportunity but also an economic obstacle to showing the clinical benefit of candidate chemopreventive drugs. Therefore, an important component of chemopreventive agent development research in recent years has been to identify earlier (than cancer) end points or biomarkers that accurately predict an agent's clinical benefit or cancer incidence -reducing effect. In many cancers, IEN is an early end point. In 2002, the AACR IEN Task Force recommended focusing chemopreventive drug development on IEN because of the close association between IEN and invasive cancer and because reducing IEN burden can benefit patients by reducing cancer risk and/or the need for invasive interventions (1). The IEN Task Force proposed several practical and feasible clinical trial designs for developing new agents to treat and prevent precancer in nine cancer target organs.

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Section: Epidemiologic and Experimental Evidencementioning

confidence: 99%

Section: Prostate Cancermentioning

confidence: 99%

Section: Colorectal Cancermentioning

confidence: 99%

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Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer—A Plan to Move Forward

Kelloff

Lippman

Dannenberg

et al. 2006

Clinical Cancer Research

Self Cite

253

196

View full text Add to dashboard Cite

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“…However, in practice it is not feasible to conduct trials using long-term interventions with food, as participants may have problems complying with the food protocol over a longer time. Because tumor development in humans can easily take 10-20 years (Kelloff et al, 2004) and human studies are costly, animal studies are conducted to examine whether a causal relationship exists in these different species, to understand mechanisms and to find potential chemopreventive agents that can be relevant for human cancer development (Corpet & Pierre, 2005). A way forward in human studies would be to investigate biomarkers of CRC incidence as early end points.…”

Section: Evidence From Human Studiesmentioning

confidence: 99%

0908 The role of red and processed meat in colorectal cancer development: A perspective

Smet¹

2016

Journal of Animal Science

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This paper is based on a workshop held in Oslo, Norway in November 2013, in which experts discussed how to reach consensus on the healthiness of red and processed meat. Recent nutritional recommendations include reducing intake of red and processed meat to reduce cancer risk, in particular colorectal cancer (CRC). Epidemiological and mechanistic data on associations between red and processed meat intake and CRC are inconsistent and underlying mechanisms are unclear. There is a need for further studies on differences between white and red meat, between processed and whole red meat and between different types of processed meats, as potential health risks may not be the same for all products. Better biomarkers of meat intake and of cancer occurrence and updated food composition databases are required for future studies. Modifying meat composition via animal feeding and breeding, improving meat processing by alternative methods such as adding phytochemicals and improving our diets in general are strategies that need to be followed up.

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“…Figure 1 shows some of the warning signs that depict risks of CRC. Further, several factors, both modifiable and nonmodifiable, exist that can either intensify or reduce the risk of CRC (Figure 2) [7][8][9][10][11][12].…”

Section: Colorectal Cancermentioning

confidence: 99%

Getting into the colon: approaches to target colorectal cancer

Patel

2014

Expert Opinion on Drug Delivery

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Colorectal Adenomas

Cited by 64 publications

References 113 publications

Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer—A Plan to Move Forward

Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer—A Plan to Move Forward

0908 The role of red and processed meat in colorectal cancer development: A perspective

Getting into the colon: approaches to target colorectal cancer

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