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ABSTRACT
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.
Disclosure of potential conflicts of interest
Penn State Research Foundation has licensed ceramide nanoliposomes to Keystone Nano, Inc. (University Park, PA). MK is co-founder and CSO of Keystone Nano.
Funding
This work was supported by the National Institutes of Health under grant P30GM103339, P01CA203628. Dr. Mark Kester was supported by grants from (R01 CA 207396,R01 CA 167535, P01 CA 171983).