Therapeutic implications of bioactive sphingolipids: A focus on colorectal cancer

Therapy of colorectal cancer (CRC), especially a subset known as locally advanced rectal cancer, is challenged by progression and recurrence. Sphingolipids, a lipid subtype with vital roles in cellular function, play an important role in CRC and impact on therapeutic outcomes. In this review we discuss how dietary sphingolipids or the gut microbiome via alterations in sphingolipids influence CRC carcinogenesis. In addition, we discuss the expression of sphingolipid enzymes in the gastro-intestinal tract, their alterations in CRC, and the implications for therapy responsiveness. Lastly, we highlight some novel therapeutics that target sphingolipid signaling and have potential applications in the treatment of CRC. Understanding how sphingolipid metabolism impacts cell death susceptibility and drug resistance will be critical toward improving therapeutic outcomes.