Dataset Information

Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges.

ABSTRACT: Chronic hand eczema (CHE) is a common and burdensome inflammatory skin condition seen in up to 10% of the population, more often in high-risk occupational workers. Topical therapeutics comprise the standard of care, but up to 65% of cases do not resolve after treatment, and moderate-to-severe cases are often resistant to topical therapeutics and require systemic options instead. To date, there are no systemic therapeutics approved to treat CHE in the United States, but several drugs are under investigation as potential treatments for CHE. The primary focus of this review is on the novel therapeutics, topical and systemic, that are under investigation in recently completed or currently ongoing trials. This review also briefly outlines the existing treatments utilized for CHE, often with limited success or extensive adverse effects. CHE represents a major challenge for physicians and patients alike, and efforts to improve the minimally invasive diagnostic tools and treatment paradigms are ongoing. In the near future, CHE patients may benefit from new topical and systemic therapeutics that specifically target abnormally expressed immune markers.

SUBMITTER: Dubin C

PROVIDER: S-EPMC7780849 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges.

Dubin Celina C Del Duca Ester E Guttman-Yassky Emma E

Therapeutics and clinical risk management 20201231

Chronic hand eczema (CHE) is a common and burdensome inflammatory skin condition seen in up to 10% of the population, more often in high-risk occupational workers. Topical therapeutics comprise the standard of care, but up to 65% of cases do not resolve after treatment, and moderate-to-severe cases are often resistant to topical therapeutics and require systemic options instead. To date, there are no systemic therapeutics approved to treat CHE in the United States, but several drugs are under in ...[more]

PMID: 33408476

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Project description:The discovery and development of small molecule cancer drugs has been revolutionised over the last decade. Most notably, we have moved from a one-size-fits-all approach that emphasized cytotoxic chemotherapy to a personalised medicine strategy that focuses on the discovery and development of molecularly targeted drugs that exploit the particular genetic addictions, dependencies and vulnerabilities of cancer cells. These exploitable characteristics are increasingly being revealed by our expanding understanding of the abnormal biology and genetics of cancer cells, accelerated by cancer genome sequencing and other high-throughput genome-wide campaigns, including functional screens using RNA interference. In this review we provide an overview of contemporary approaches to the discovery of small molecule cancer drugs, highlighting successes, current challenges and future opportunities. We focus in particular on four key steps: Target validation and selection; chemical hit and lead generation; lead optimization to identify a clinical drug candidate; and finally hypothesis-driven, biomarker-led clinical trials. Although all of these steps are critical, we view target validation and selection and the conduct of biology-directed clinical trials as especially important areas upon which to focus to speed progress from gene to drug and to reduce the unacceptably high attrition rate during clinical development. Other challenges include expanding the envelope of druggability for less tractable targets, understanding and overcoming drug resistance, and designing intelligent and effective drug combinations. We discuss not only scientific and technical challenges, but also the assessment and mitigation of risks as well as organizational, cultural and funding problems for cancer drug discovery and development, together with solutions to overcome the 'Valley of Death' between basic research and approved medicines. We envisage a future in which addressing these challenges will enhance our rapid progress towards truly personalised medicine for cancer patients.

Project description:IntroductionAboriginal and Torres Strait Islander Australians living in remote locations suffer disproportionately from chronic hepatitis B (CHB). Defining the temporospatial epidemiology of the disease-and assessing the ability of local clinicians to deliver optimal care-is crucial to improving patient outcomes in these settings.MethodsThe demographic, laboratory and radiology findings in all patients diagnosed with CHB after 1990, and presently residing in remote Far North Queensland (FNQ), tropical Australia, were correlated with their management and clinical course.ResultsOf the 602 patients, 514 (85%) identified as Aboriginal and Torres Strait Islander Australians, 417 (69%) of whom had Torres Strait Islander heritage. Among the 514 Aboriginal and Torres Strait Islander Australians, there were only 61 (12%) born after universal postnatal vaccination was introduced in 1985. Community CHB prevalence varied significantly across the region from 7/1707 (0.4%) in western Cape York to 55/806 (6.8%) in the Eastern Torres Strait Islands. Although 240/602 (40%) are engaged in care, with 65 (27%) meeting criteria for antiviral therapy, only 43 (66%) were receiving this treatment. Among 537 with complete data, 32 (6%) were cirrhotic, of whom 15 (47%) were engaged in care and 10 (33%) were receiving antiviral therapy. Only 64/251 (26%) in whom national guidelines would recommend hepatocellular carcinoma (HCC) surveillance are receiving screening, however, only 20 patients have been diagnosed with HCC since 1999.ConclusionVaccination has had a dramatic effect on CHB prevalence in FNQ in only a generation. However, although engagement in care is the highest in Australia, this is not translating into initiation of antiviral therapy in all those that should be receiving it, increasing their risk of developing cirrhosis and HCC. New strategies are necessary to improve the care of Indigenous Australians living with CHB to reduce the morbidity and mortality of this preventable disease.

Dataset Information

Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges.

Publications

Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges.

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