Future perspectives in melanoma research. Meeting report from the “Melanoma Bridge. Napoli, December 2nd-4th 2012”

Abstract

Recent insights into the genetic and somatic aberrations have initiated a new era of rapidly evolving targeted and immune-based treatments for melanoma. After decades of unsuccessful attempts to finding a more effective cure in the treatment of melanoma now we have several drugs active in melanoma. The possibility to use these drugs in combination to improve responses to overcome the resistance, to potentiate the action of immune system with the new immunomodulating antibodies, and identification of biomarkers that can predict the response to a particular therapy represent new concepts and approaches in the clinical management of melanoma. The third “Melanoma Research: “A bridge from Naples to the World” meeting, shortened as “Bridge Melanoma Meeting” took place in Naples, December 2 to 4th, 2012. The four topics of discussion at this meeting were: advances in molecular profiling and novel biomarkers, combination therapies, novel concepts toward integrating biomarkers and therapies into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage, and the knowledge gained from the biology of tumor microenvironment across different tumors as a bridge to impact on prognosis and response to therapy in melanoma. This international congress gathered more than 30 international faculty members who in an interactive atmosphere which stimulated discussion and exchange of their experience regarding the most recent advances in research and clinical management of melanoma patients.

Immunomodulatory pathways regulate expression of a spliced FKBP51 isoform in lymphocytes of melanoma patients

“…It is worth noting that PDL‐1 expression in melanoma is extremely heterogeneous (Ascierto et al., ), with intra‐ and intertumour variability. Our finding suggests that such a variability may depend, at least in part, on the ability of melanoma to produce alternative splicing of FKBP5 gene aberrantly expressed.…”

High expression of FOXP3 in primary melanoma is associated with tumour progression

“…Recently, multiple articles have been published on the prognostic and predictive value of immune infiltrates in cancer, and data collected from large cohorts of human cancer have demonstrated that the immune classification of malignant tumours adds additional information to the currently used tumour staging method (American Joint Committee on Cancer/Union for International Cancer Control tumour thickness, nodes, metastasis classification) . FOXP3 is a further candidate that may increase outcome predictions in melanoma.…”

Trametinib in metastatic melanoma

“…Next-generation sequencing and whole exome sequencing have been utilized to characterize the genomic landscape of melanoma, identifying the common genetic alterations that have led to the development of novel agents. Future translational research will no doubt improve the landscape of melanoma treatment hopefully leading to improvements in PFS and OS [103].…”

“…Many have been evaluated in melanoma but remain to be clinically validated [103]. Serum levels of lactate dehydrogenase, alkaline phosphatase, melanoma inhibitory activity, tyrosinase and melana/mart1 detected by RT-PCR correlate with clinical stage and tumor progression, but only serum LDH has shown be to a strong independent prognostic factor in metastatic melanoma [103,107]. S100B has been considered a prognostic marker in stage III and IV melanoma as it relates to the tumor burden and can reflect clinical stage and progression; however, it does not provide independent prognostic information.…”

“…The challenge will now be to find the perfect combination of these agents that works to improve survival and delay resistance. Future trials should combine the 'best in class' of drugs rather than trials investigating single agents in the same class [103].…”