The first goal of the Melanoma Research Program is to improve risk stratification by identifying markers that are relevant to prognosis in primary melanoma and improve risk stratification. Our second goal is to study the biologic heterogeneity of melanoma by examining cell cycle regulators, the role of microRNA alterations, and specific functions of signaling pathways and resistance to treatment. Our third goal is to develop novel therapeutic modalities for melanoma.
Recently, we completed studies that examined the impact of histological, pathological, and immunological markers on prognosis by using novel sera and blood-based assays. Members of the Program have explored a new platform of miRNA targeting, tested a novel NOTCH inhibitor in melanoma and expanded their studies on immunologic approaches including anti-CTLA-4 therapy in combination with other treatments.
Epidemiology and Prevention
- We investigated lymphovascular invasion (LVI) in primary melanoma using endothelial markers D2-40 and CD34 in detection markers and their clinical implications compared to routine histology. We found that D2-40 and CD34 increase detection of LVI in primary melanoma and that cases missed by routine histology have prognostic relevance (Rose AE et al., Am J Surg Pathol. 2011).
- We used highly sensitive BRAF mutation detection methods and observed substantial evidence for heterogeneity of the BRAF(V600E) mutation both within individual melanoma tumor specimens and among multiple specimens from individual patients. Given the varied clinical responses of patients to BRAF inhibitor therapy, this suggests that determining possible associations between clinical outcomes and intra- and inter-tumor heterogeneity may be fruitful. (Yancovitz M et al., PLoS One. 2012).
- We tested the hypothesis that melanoma patients who develop brain metastasis as the isolated first visceral site have distinct clinicopathological features at the time of primary melanoma diagnosis and determined that this type of brain metastasis is a distinct clinicopathological entity. (Ma MW et al., Neuro Oncol. 2012).
We investigated the role of:
- Altered cell cycle regulators and immune modulators in Melanoma progression.
- MicroRNA regulation in melanoma progression.
- Altered signaling pathways in melanoma progression and resistance to treatment.
- Anti-CTLA-4 therapy in combination with radiation treatment and in combination with cytotoxin.
- The role of BRD4 in melanoma maintenance.