Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014.

摘要: The fourth “Melanoma Bridge Meeting” took place in Naples, December 3–6th, 2014. four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News Immunotherapy, Tumor Microenvironment Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances tumor biology immunology have led to the development of new targeted immunotherapeutic agents that prolong progression-free survival (PFS) overall (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors well other signaling inhibitors, are being tested with either monotherapy or combination, all yielded promising results. These include receptor tyrosine kinases (BRAF, MEK, VEGFR), phosphatidylinositol 3 (PI3K) [PI3K, AKT, mammalian target rapamycin (mTOR)], activators apoptotic pathway, cell cycle (CDK4/6). Various locoregional interventions including radiotherapy surgery still valid approaches treatment advanced can be integrated novel therapies. Intrinsic, adaptive acquired resistance occur BRAF where most responses short-lived. Given reactivation MAPK through several distinct mechanisms is responsible majority resistance, it logical combine targets downstream pathway. For example, combination BRAF/MEK (e.g., dabrafenib/trametinib) been demonstrated improve compared monotherapy. Application technologies sequencing proven useful a tool identification pathway-alternative mechanism designing combinatorial therapies those between AKT inhibitors. Improved rates also observed immune-targeted melanoma. Immune-modulating antibodies came forefront anti-CTLA-4, programmed death-1 (PD-1) PD-1 ligand 1 (PD-L1) blocking result durable subset patients. Agents targeting immune inhibitory Tim-3) stimulating CD137) receptors adoptive transfer demonstrate clinical benefit well. studied attempt produce longer-term than more typically seen therapy. Other combinations cytotoxic chemotherapy angiogenesis changing evolving landscape therapeutic options evaluated prevent delay further patient population. This meeting’s specific focus on immunotherapy. Both different immunotherapies were discussed. Similarly previous meetings, importance biomarkers application markers diagnosis, prognosis prediction response an integral part meeting. emphasis supports concepts toward integrating into contemporary management across entire spectrum disease stage. Translation knowledge gained from microenvironment tumors represents bridge impact