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Updated: Jul 26, 2025
A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
Published on: June 8, 2022
Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer
Saida Mebarek1, Najwa Skafi2, Leyre Brizuela1
1CNRS UMR 5246, INSA Lyon, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), 69622 Lyon, France.
Abstract:
Prostate cancer (PC) is the second most common cancer in men worldwide. More than 65% of men diagnosed with PC are above 65. Patients with localized PC show high long-term survival, however with the disease progression into a metastatic form, it becomes incurable, even after strong radio- and/or chemotherapy. Sphingosine 1-phosphate (S1P) is a bioactive lipid that participates in all the steps of oncogenesis including tumor cell proliferation, survival, migration, invasion, and metastatic spread. The S1P-producing enzymes sphingosine kinases 1 and 2 (SK1 and SK2), and the S1P degrading enzyme S1P lyase (SPL), have been shown to be highly implicated in the onset, development, and therapy resistance of PC during the last 20 years. In this review, the most important studies demonstrating the role of S1P and S1P metabolic partners in PC are discussed. The different in vitro, ex vivo, and in vivo models of PC that were used to demonstrate the implication of S1P metabolism are especially highlighted. Furthermore, the most efficient molecules targeting S1P metabolism that are under preclinical and clinical development for curing PC are summarized. Finally, the possibility of targeting S1P metabolism alone or combined with other therapies in the foreseeable future as an alternative option for PC patients is discussed. Research Strategy: PubMed from INSB was used for article research. First, key words "prostate & sphingosine" were used and 144 articles were found. We also realized other combinations of key words as "prostate cancer bone metastasis" and "prostate cancer treatment". We used the most recent reviews to illustrate prostate cancer topic and sphingolipid metabolism overview topic.
Insights
This review highlights the role of sphingosine 1-phosphate (S1P) metabolism in prostate cancer (PC) progression and therapy resistance. Targeting S1P pathways offers a promising therapeutic strategy for advanced PC.
Area of Science:
- Oncology
- Biochemistry
- Lipid Metabolism
Background:
- Prostate cancer (PC) is a leading cause of cancer death in men, with metastatic disease being incurable.
- Sphingosine 1-phosphate (S1P) is a bioactive lipid involved in cancer cell proliferation, survival, migration, invasion, and metastasis.
- Dysregulation of S1P metabolism, involving sphingosine kinases (SK1/SK2) and S1P lyase (SPL), is implicated in PC development and treatment resistance.
Purpose of the Study:
- To review key studies on the role of S1P and its metabolic partners in prostate cancer.
- To highlight various in vitro, ex vivo, and in vivo models used to study S1P metabolism in PC.
- To summarize molecules targeting S1P metabolism in preclinical and clinical development for PC treatment.
Main Methods:
- Literature review using PubMed with keywords such as "prostate & sphingosine", "prostate cancer bone metastasis", and "prostate cancer treatment".
- Focus on recent reviews to cover PC and sphingolipid metabolism.
- Analysis of studies demonstrating the implication of S1P metabolism in PC progression and therapeutic resistance.
Main Results:
- S1P signaling and its metabolic enzymes (SK1, SK2, SPL) are crucial in PC oncogenesis, progression, and resistance to therapy.
- Various experimental models have confirmed the involvement of S1P metabolism in PC.
- Several molecules targeting S1P metabolism are in preclinical and clinical development.
Conclusions:
- S1P metabolism is a significant factor in prostate cancer progression and therapeutic outcomes.
- Targeting S1P metabolism, alone or in combination with other therapies, presents a potential future treatment strategy for PC patients.
- Further research and clinical development of S1P-targeting agents are warranted for effective PC management.
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