Abstract
Tumor microenvironment is a network of complex cellular and molecular systems where cells will gain specific phenotypes and specific functions that would drive tumorigenesis. In skin cancers, tumor microenvironment is characterized by tumor infiltrating immune cells that sustain immune suppression, mainly lymphocytes. Melanoma cellular heterogeneity can be described on genetic, proteomic, transcriptomic and metabolomic levels. Melanoma cells display a metabolic reprogramming triggered by both genetic alterations and adaptation to a microenvironment that lacks nutrients and oxygen supply. Tumor cells present clear metabolic adaptations and identifying deregulated glycolysis pathway could offer new therapy targets. Moreover, the immune cells (T lymphocytes, macrophages, NK cells, neutrophils and so on) that infiltrate melanoma tumors have metabolic particularities that, upon interaction within tumor microenvironment, would favor tumorigenesis. Analyzing both tumor cell metabolism and the metabolic outline of immune cells can offer innovative insights in new therapy targets and cancer therapeutical approaches. In addition to already approved immune- and targeted therapy in melanoma, approaching metabolic check-points could improve therapy efficacy and hinder resistance to therapy.
Highlights
Metabolic requirements change when cells enter the proliferation process this is due to the fact that cell metabolism needs to sustain a different cellular stage
Normal cells when proliferate have the same metabolic needs to cancer cells, this raises the issue of targeting a metabolic pathways that can be common to normal and cancer cells, finding the therapeutic window for an anticancer cell metabolism is still a matter of intense study
In melanoma cells various transcription factors regulate in parallel BRAF and glycolysis pathway. These transcription factors (e.g., hypoxia inducible factors (HIFs)-1a, MYC, MLXIP) regulate glycolysis downstream of BRAFV600, and if concomitant inhibition is done, apoptosis is induced in cells that otherwise are resistant to BRAF inhibitor alone
Summary
Tumor microenvironment is characterized by tumor infiltrating immune cells that sustain immune suppression, mainly lymphocytes. Melanoma cells display a metabolic reprogramming triggered by both genetic alterations and adaptation to a microenvironment that lacks nutrients and oxygen supply. Tumor cells present clear metabolic adaptations and identifying deregulated glycolysis pathway could offer new therapy targets. The immune cells (T lymphocytes, macrophages, NK cells, neutrophils and so on) that infiltrate melanoma tumors have metabolic particularities that, upon interaction within tumor microenvironment, would favor tumorigenesis. Analyzing both tumor cell metabolism and the metabolic outline of immune cells can offer innovative insights in new therapy targets and cancer therapeutical approaches.
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