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Bi-Directional Signaling Between Melanoma And The Microenvironment Generates A Protective Niche That Mediates Therapeutic Escape, Inna Fedorenko
Bi-Directional Signaling Between Melanoma And The Microenvironment Generates A Protective Niche That Mediates Therapeutic Escape, Inna Fedorenko
USF Tampa Graduate Theses and Dissertations
Very few cancer patients are cured through drug therapy alone, with the majority exhibiting acquired resistance. To date, most studies of therapeutic escape have focused upon tumor-intrinsic mechanisms of drug resistance with little attention paid to the role of normal host cells in preventing complete tumor eradication. In the present study we implicate co-operative bi-directional signaling between melanoma cells and fibroblasts in the generation of a pro-survival niche that mediates drug resistance. Mass-spectrometry based phosphoproteomics was used to show that BRAF inhibition and chemotherapy drugs enhanced the survival of both melanoma cells and fibroblasts through the induction of fibronectin (FN)/integrin …
Potential Targeted Therapeutic Strategies For Overcoming Resistance In Braf Wild Type Melanoma, Vito William Rebecca
Potential Targeted Therapeutic Strategies For Overcoming Resistance In Braf Wild Type Melanoma, Vito William Rebecca
USF Tampa Graduate Theses and Dissertations
Melanoma manifests itself from the malignant transformation of melanocytes and represents the deadliest form of skin cancer, being responsible for the disproportionate majority of all skin cancer deaths. The 2002 discovery that 50% of all melanoma patients possess activating BRAF mutations ignited a significant paradigm shift in the way the melanoma field approached research and how patients were treated [1]. The era of targeted therapy had begun and with it came successful targeted BRAF inhibitor therapy regimens, which have accomplished improved clinical benefit (response rate, progression free survival, and overall survival) compared with treatment with chemotherapy in three phase III …