Sphingolipids and Lymphomas: A Double-Edged Sword

SIMPLE SUMMARY: Cancer is an incredibly smart disease, so much so that it can entirely reprogram our cells’ metabolism to ensure its survival and dissemination. Lymphomas are a particularly interesting group of cancers because they are very diverse and exhibit complex pathogenic mechanisms that can make them clinically challenging. Many of these mechanisms involve the dysregulation of a biologically relevant family of lipids known as sphingolipids. These molecules are involved in virtually every cellular process and therefore studying them in this context is crucial. However, sphingolipid biochemistry is intricate and the synergistic and antagonic effects of different sphingolipid species with one another has long puzzled scientists. This duality is also observed in cancer, but research specifically focusing on lymphomas is limited. Could novel biomarkers and therapies against lymphomas be hiding within this pathway? ABSTRACT: Lymphomas are a highly heterogeneous group of hematological neoplasms. Given their ethiopathogenic complexity, their classification and management can become difficult tasks; therefore, new approaches are continuously being sought. Metabolic reprogramming at the lipid level is a hot topic in cancer research, and sphingolipidomics has gained particular focus in this area due to the bioactive nature of molecules such as sphingoid bases, sphingosine-1-phosphate, ceramides, sphingomyelin, cerebrosides, globosides, and gangliosides. Sphingolipid metabolism has become especially exciting because they are involved in virtually every cellular process through an extremely intricate metabolic web; in fact, no two sphingolipids share the same fate. Unsurprisingly, a disruption at this level is a recurrent mechanism in lymphomagenesis, dissemination, and chemoresistance, which means potential biomarkers and therapeutical targets might be hiding within these pathways. Many comprehensive reviews describing their role in cancer exist, but because most research has been conducted in solid malignancies, evidence in lymphomagenesis is somewhat limited. In this review, we summarize key aspects of sphingolipid biochemistry and discuss their known impact in cancer biology, with a particular focus on lymphomas and possible therapeutical strategies against them.