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Targeting sphingolipid metabolism in head and neck cancer: rational therapeutic potentials
Thomas H Beckham1, Saeed Elojeimy, Joseph C Cheng
1Medical University of South Carolina, Department of Biochemistry & Molecular Biology, 173 Ashley Avenue, MSC 504, Charleston, South Carolina 29425-5040, USA. beckham@musc.edu
Importance Of The Field:
Ceramide accumulation has been shown to be a conserved mechanism of apoptosis initiation in normal physiological processes as well as in response to cancer treatments. Therefore, it is unsurprising that many cancers develop aberrations of sphingolipid metabolism that prevent the accumulation of ceramide, whether by reduction of ceramide generation or by enhanced ceramide catabolism, particularly dangerous when catabolism leads to generation of pro-tumor sphingosine-1-phosphate and ceramide-1-phosphate. Numerous studies have now implicated dysregulation of sphingolipid metabolism in head and neck cancers.
Areas Covered In This Review:
This review highlights the importance of sphingolipid metabolism and brings sphingolipid metabolism to the forefront in the investigation of novel therapies for head and neck cancer. It reviews sphingolipid-centric therapies under investigation in preclinical and clinical trials of cancers of the head and neck.
What The Reader Will Gain:
The roles of sphingolipids and sphingolipid metabolism in cancer are reviewed and the reader will be brought up to date with discoveries in the field of sphingolipid metabolism in head and neck cancer.
Take Home Message:
As treatments for head and neck cancers are currently limited, the potential of targeting sphingolipid metabolism should be taken into consideration as we seek novel ways to combat this group of tumors.
Insights
Sphingolipid metabolism is dysregulated in head and neck cancers, often preventing ceramide accumulation. Targeting sphingolipid metabolism offers a promising therapeutic strategy for these challenging tumors.
Area of Science:
- Oncology
- Biochemistry
- Cancer Therapeutics
Background:
- Ceramide accumulation is a key apoptosis initiator in physiological processes and cancer treatment.
- Aberrations in sphingolipid metabolism, including reduced ceramide generation or enhanced catabolism, are common in cancers.
- Dysregulated sphingolipid metabolism, producing pro-tumor metabolites like sphingosine-1-phosphate, is implicated in head and neck cancers.
Purpose of the Study:
- To highlight the critical role of sphingolipid metabolism in head and neck cancer.
- To review sphingolipid-centric therapies currently under investigation for head and neck cancer.
Main Methods:
- This review synthesizes current research on sphingolipid metabolism in head and neck cancer.
- It examines preclinical and clinical trials of sphingolipid-targeted therapies.
Main Results:
- Sphingolipids and their metabolic pathways play significant roles in cancer development.
- Recent discoveries in sphingolipid metabolism specific to head and neck cancer are presented.
Conclusions:
- Current treatments for head and neck cancers are limited.
- Targeting sphingolipid metabolism presents a novel therapeutic avenue for combating these tumors.
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