Charles H. Adelmann

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Vemurafenib and dabrafenib selectively inhibit the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) kinase, resulting in high response rates and increased survival in melanoma. Approximately 22% of individuals treated with vemurafenib develop cutaneous squamous cell carcinoma (cSCC) during therapy. The prevailing explanation for this is drug-induced(More)
Sorafenib is U.S. Food and Drug Adminstration-approved for the treatment of renal cell carcinoma and hepatocellular carcinoma and has been combined with numerous other targeted therapies and chemotherapies in the treatment of many cancers. Unfortunately, as with other RAF inhibitors, patients treated with sorafenib have a 5% to 10% rate of developing(More)
Protein kinases are mutated or otherwise rendered constitutively active in numerous cancers where they are attractive therapeutic targets with well over a dozen kinase inhibitors now being used in therapy. While fluorescent sensors have capacity to measure changes in kinase activity, surprisingly they have not been utilized for biomarker studies. A(More)
Cutaneous squamous cell carcinoma (cuSCC) comprises 15-20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis(More)
ACKNOWLEDGMENTS The Italian Melanoma Intergroup (IMI) includes the following additional members who participated as investigators in this study and should be considered as co-authors: Nicola Mozzillo (Istituto Nazionale Tumori, Napoli, Italy), Panagiotis Paliogiannis (Chirurgia, Microchirurgia e Scienze Mediche, Università di Sassari, Italy), PaolaQueirolo(More)
BRAF inhibitor (BRAFi) therapy is associated with the induction of neoplasia, most commonly cutaneous squamous cell carcinoma (cuSCC). This toxicity is explained in part by "paradoxical ERK activation," or the hyperactivation of ERK signaling by BRAFi in BRAF wild-type cells. However, the rate of cuSCC induction varies widely among BRAFi. To explore this(More)
Sorafenib is U.S. Food and Drug Adminstration–approved for the treatment of renal cell carcinoma and hepatocellular carcinomaandhas been combinedwithnumerous other targeted therapies and chemotherapies in the treatment of many cancers. Unfortunately, as with other RAF inhibitors, patients treated with sorafenib have a 5% to 10% rate of developing cutaneous(More)
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