Dataset Information

Cancer Prevention: Obstacles, Challenges and the Road Ahead.

ABSTRACT: Approaches to reduce the global burden of cancer include two major strategies: screening and early detection and active preventive intervention. The latter is the topic of this Commentary and spans a broad range of activities. The genetic heterogeneity and complexity of advanced cancers strongly support the rationale for early interruption of the carcinogenic process and an enhanced focus on prevention as a priority strategy to reduce the burden of cancer; however, the focus of cancer prevention management should be on individuals at high risk and on primary localized disease in which screening and detection should also play a vital role. The timing and dose of (chemo-)preventive intervention also affects response. The intervention may be ineffective if the target population is very high risk or already presenting with preneoplastic lesions with cellular changes that cannot be reversed. The field needs to move beyond general concepts of carcinogenesis to targeted organ site prevention approaches in patients at high risk, as is currently being done for breast and colorectal cancers. Establishing the benefit of new cancer preventive interventions will take years and possibly decades, depending on the outcome being evaluated. We also propose that comparative effectiveness research designs and the value of information obtained from large-scale prevention studies are necessary in order for preventive interventions to become a routine part of cancer management.

SUBMITTER: Meyskens FL

PROVIDER: S-EPMC4907357 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Cancer Prevention: Obstacles, Challenges and the Road Ahead.

Meyskens Frank L FL Mukhtar Hasan H Rock Cheryl L CL Cuzick Jack J Kensler Thomas W TW Yang Chung S CS Ramsey Scott D SD Lippman Scott M SM Alberts David S DS

Journal of the National Cancer Institute 20151107 2

Approaches to reduce the global burden of cancer include two major strategies: screening and early detection and active preventive intervention. The latter is the topic of this Commentary and spans a broad range of activities. The genetic heterogeneity and complexity of advanced cancers strongly support the rationale for early interruption of the carcinogenic process and an enhanced focus on prevention as a priority strategy to reduce the burden of cancer; however, the focus of cancer prevention ...[more]

PMID: 26547931

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Project description:Morphea is a rare autoimmune condition causing inflammation and sclerosis of the skin and underlying soft tissue. It is characterized by periods of activity (inflammation admixed with fibrosis), ultimately resulting in permanent damage (pigment change and tissue loss). Damage resulting from unchecked activity can lead to devastating, permanent cosmetic and functional sequelae including hair loss; cutaneous, soft tissue and bony atrophy; joint contractures; and growth restriction of the affected body site in children. This makes the early identification of activity and initiation of appropriate treatment crucial to limiting damage in morphea. To this end, recent investigative work has focused on validation of clinical, biomarker, imaging, and histologic outcomes aimed at accurately quantifying activity and damage. Despite promising results, further work is needed to better validate these measures before they can be used in the clinic and research settings. Although there has been recent approval of less toxic, targeted therapies for many inflammatory skin conditions, none have been systematically investigated in morphea. The mainstays of treatment for active morphea are corticosteroids and methotrexate. These are often limited by substantial toxicity. The paucity of new treatments for morphea is the result of a lack of studies examining its pathogenesis, with many reviews extrapolating from research in systemic sclerosis. Recent studies have demonstrated the role of dysregulated immune and fibrotic pathways in the pathogenesis of morphea, particularly interferon (IFN) gamma related pathways. Active morphea lesions have been found to display an inflammatory morphea signature with CXCR3 receptor ligands, as well as a distinct fibrotic signature reflecting fibroblast activation and collagen production. CXCL9 and 10 have been associated with increased measures of disease activity. While immune dysfunction is thought to play the primary role in morphea pathogenesis, there are other factors that may also contribute, including genetic predisposition, environmental factors, and vascular dysregulation. There remains an essential need for further research to elucidate the pathogenesis of morphea and the mode of action of dysregulated upstream and downstream immune and fibrotic pathways. These studies will allow for the discovery of novel biomarkers and targets for therapeutic development.

Dataset Information

Cancer Prevention: Obstacles, Challenges and the Road Ahead.

Publications

Cancer Prevention: Obstacles, Challenges and the Road Ahead.

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