Fenretinide in Cancer and Neurological Disease: A Two-Face Janus Molecule

Area of Science:

• Pharmacology
• Oncology
• Neuroscience

Background:

• Chemotherapeutic drug repositioning is emerging for neurological diseases, driven by shared biological pathways and inverse cancer-neurodegeneration comorbidity.
• Fenretinide (all-trans-N-(4-hydroxyphenyl) retinamide, 4-HPR), a synthetic retinoid derivative, was initially developed for anticancer therapy due to its antitumor effects and low toxicity.
• 4-HPR's ability to modulate diverse biological pathways has led to its investigation for diseases beyond cancer, showcasing its pleiotropic nature.

Purpose of the Study:

• To review preclinical and clinical findings on fenretinide (4-HPR).
• To discuss the therapeutic role of fenretinide in both cancer and neurological diseases.
• To highlight the hormetic behavior of fenretinide as a pleiotropic molecule.

Main Methods:

• Literature review of preclinical studies.
• Analysis of clinical trial data.
• Synthesis of pharmacological data on fenretinide's biological pathways.

Main Results:

• Fenretinide demonstrates significant potential in both oncological and neurodegenerative disease contexts.
• The molecule exhibits a broad spectrum of pharmacological effects, influencing multiple biological pathways.
• Evidence suggests a hormetic dose-response relationship for fenretinide's therapeutic actions.

Conclusions:

• Fenretinide is a promising drug candidate for repositioning in neurological disorders.
• Its pleiotropic and hormetic characteristics warrant further investigation for diverse therapeutic applications.
• Understanding fenretinide's complex biological actions is key to optimizing its clinical use in cancer and neurodegeneration.