Our Clinical Trials Continually updated listing of our clinical trials for melanoma 
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Melanomas can arise from the skin, mucous membranes, or eyes. Members of our melanoma research team are leaders in the fields of immunology, medical oncology, pathology, radiology, radiation oncology, and surgery. We have participated in research studying families in which multiple members have been diagnosed with melanoma.
We are leaders in the development of immune therapies, vaccines, and targeted therapies for melanoma, and we were the first to show the effectiveness of monoclonal antibodies for the treatment of solid tumors. Our team also has developed surgical techniques and new radiation therapies, including brachytherapy and stereotactic radiosurgery, for the treatment of melanoma.
Among our recent research accomplishments:
Detection, Diagnosis, and Prognosis
- Using molecular profiling, we've shown that desmoplastic melanoma and clear-cell sarcoma are distinct subsets of melanoma with different molecular and clinical characteristics; these studies have led to changes in the clinical management of desmoplastic melanoma and the eligibility of patients with clear cell sarcoma for clinical trials. Desmoplastic melanoma has a distinct molecular signature, with strong expression of genes involved in extracellular matrix production, a much-reduced incidence of regional metastases, and low mortality in a subset of patients whose tumors have desmoplasia throughout. Clear-cell sarcoma is actually a genomic subtype of melanoma, distinct from sarcomas; we have identified several therapeutic targets (pMEL17, TYRP2/DCT, MELAN-A/MART-1, and SOX10 for cancer vaccine strategies, and FGFR1 for tyrosine kinase inhibition). As a result of these observations, these patients are now eligible for DNA vaccine trials for pMEL17 and TYRP2/DCT. J Invest Dermatol 2005;124:412-418. [PubMed Abstract]; Ann Surg Oncol 2005;12:207-213. [PubMed Abstract]
Therapeutic Approaches
- The V600E activating mutations in BRAF, the prevalent activating mutation in the majority of melanomas, leads to a requirement for HSP90 binding to maintain stability of mutant BRAF. This finding has led to clinical trials at MSKCC of HSP90 inhibition with the investigational agent 17-AAG. Proc Natl Acad Sci 2005;103:57-62. [PubMed Abstract]
- Activated mutant BRAF in melanoma also constitutively signals through the MAP kinase pathway, leading to exquisite and specific sensitivity to small-molecule inhibitors of the MEK protein with consequent down-regulation of cyclin D1 expression and G1 arrest. Clinical trials of agents that inhibit MEK are in progress. Nature 2006;439:358-362. [PubMed Abstract]
- Immunological approaches to melanoma, perhaps the oldest tumor target for immunotherapy, have produced exciting results in the veterinary setting. Xenogeneic DNA vaccines developed at MSKCC against tyrosinase family antigens -- immune targets discovered at MSKCC -- were shown in collaborative clinical trials with the Animal Medical Center of New York to induce durable complete responses and unexpectedly prolonged survival in dogs with high-risk and metastatic melanoma. These observations have led to large-scale animal field trials following licensing of vaccines to Merial, Ltd and approval by the US Department of Agriculture for a commercial launch of the tyrosinase DNA vaccine as a treatment for animals. Clinical trials in patients with melanoma are now in progress.
- Our investigators have identified a novel immunologic cell type in the spleens and other organs of mice. These cells share properties of dendritic cells (DC) and natural killer (NK) cells, as they can stimulate naïve T cells, produce high levels of interferon-gamma, and lyse targets. In addition, NKDCs can be expanded by the cytokine Flt3 ligand and are able to reduce melanoma lung metastases in a murine model. Currently, these cells are being studied in detail to optimize their use in immunotherapy in mice; an analogous cell type is being sought in human blood. J Immunol 2005;174:2612-2618. [PubMed Abstract]; FASEB J 2006;20:982-984. [PubMed Abstract]; Cancer Res. 2006;66:10497-10504. [PubMed Abstract]
- We found that a six-week schedule of temozolomide, in combination with thalidomide or PEGylated interferon-alfa, is an active combination for metastatic disease, providing the basis for cooperative group trials; this regimen is now commonly used in the United States. Temozolomide therapy induces a specific CD4+ T cell lymphopenia, increasing the risk of opportunistic infections; this effect has changed the way we monitor for toxicity in clinical practice and in clinical trials. Cancer 2006;106:2445-2451. [PubMed Abstract]
