Toward lung regeneration.

New England Journal of Medicine (Impact Factor: 54.42). 05/2011; 364(19):1867-8. DOI: 10.1056/NEJMe1101800
Source: PubMed
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    ABSTRACT: In 1976, the detection of estrogen-receptor expression in melanomas ushered in the era of targeted therapy in melanoma, although we did not use that term back then.(1) In 1992, Cocconi et al. found that dacarbazine plus tamoxifen provided a higher response rate and longer survival than dacarbazine, but only in women.(2) Subsequently, whether melanoma cells express estrogen receptors was questioned, and the efficacy of tamoxifen could not be confirmed. Since then, the drug has not been used to treat melanoma. However, molecular analysis of tumors has revealed specific growth-promoting pathways in human cancers that have become targets for therapy. BRAF . . .
    New England Journal of Medicine 06/2011; 364(26):2547-8. DOI:10.1056/NEJMe1105792 · 54.42 Impact Factor
  • Revue des Maladies Respiratoires Actualites 10/2011; 3(5):466–472. DOI:10.1016/S1877-1203(11)70145-8
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    ABSTRACT: Therapeutic resistance remains a major cause of cancer-related deaths. Resistance can occur from the outset of treatment or as an acquired phenomenon after an initial clinical response. Therapeutic resistance is an almost universal phenomenon in the treatment of metastatic cancers. The advent of molecularly targeted treatments brought greater efficacy in patients whose tumors express a particular target or molecular signature. However, resistance remains a predictable challenge. This article provides an overview of somatic genomic events that confer resistance to cancer therapies. Some examples, including BCR-Abl, EML4-ALK, and the androgen receptor, contain mutations in the target itself, which hamper binding and inhibitory functions of therapeutic agents. There are also examples of somatic genetic changes in other genes or pathways that result in resistance by circumventing the inhibitor, as in resistance to trastuzumab and BRAF inhibitors. Yet other examples results in activation of cytoprotective genes. The fact that all of these mechanisms of resistance are due to somatic changes in the tumor's genome makes targeting them selectively a feasible goal. To identify and validate these changes, it is important to obtain biopsies of clinically resistant tumors. A rational consequence of this evolving knowledge is the growing appreciation that combinations of inhibitors will be needed to anticipate and overcome therapeutic resistance.
    Frontiers in Pharmacology 10/2011; 2:59. DOI:10.3389/fphar.2011.00059


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