Nature reviews. Cancer
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Nature reviews. Cancer · Dec 2014
ReviewAryl hydrocarbon receptor ligands in cancer: friend and foe.
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is best known for mediating the toxicity and tumour-promoting properties of the carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly referred to as ‘dioxin’. AHR influences the major stages of tumorigenesis — initiation, promotion, progression and metastasis — and physiologically relevant AHR ligands are often formed during disease states or during heightened innate and adaptive immune responses. ⋯ This suggests that the AHR is chronically activated in tumours, thus facilitating tumour progression. This Review discusses the role of AHR in tumorigenesis and the potential for therapeutic modulation of its activity in tumours.
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The knowledge and tools to cure many cancer patients exist in developed countries but are unavailable to many who live in the developing world, resulting in unnecessary loss of life. Bringing cancer care to the poor, particularly to low-income countries, is a great challenge, but it is one that we believe can be met through partnerships, careful planning and a set of guiding principles. ⋯ It is also critical that these programmes include implementation research to determine programmatic efficacy, where gaps in care still exist and where improvements can be made. This article discusses these issues using the example of Rwanda's expanding national cancer programme.
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Nature reviews. Cancer · Jul 2014
ReviewTargeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond.
The identification of mutationally activated BRAF in many cancers altered our conception of the part played by the RAF family of protein kinases in oncogenesis. In this Review, we describe the development of BRAF inhibitors and the results that have emerged from their analysis in both the laboratory and the clinic. We discuss the spectrum of RAF mutations in human cancer and the complex interplay between the tissue of origin and the response to RAF inhibition. Finally, we enumerate mechanisms of resistance to BRAF inhibition that have been characterized and postulate how strategies of RAF pathway inhibition may be extended in scope to benefit not only the thousands of patients who are diagnosed annually with BRAF-mutated metastatic melanoma but also the larger patient population with malignancies harbouring mutationally activated RAF genes that are ineffectively treated with the current generation of BRAF kinase inhibitors.