Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy

Area of Science:

• Oncology
• Biochemistry
• Pharmacology

Background:

• Cancer cells exhibit altered metabolism, including increased de novo lipogenesis.
• Fatty acid (FA) synthesis enzymes are over-expressed in cancer, and their inhibition demonstrates antitumor effects.
• Fatty acid synthase (FASN) is a key enzyme in FA synthesis and a promising therapeutic target in oncology.

Purpose of the Study:

• To review the lipogenic phenotype of cancer.
• To explore the exploitation of this phenotype for cancer therapy using FASN inhibitors.
• To emphasize orlistat as a potential repurposing drug for cancer treatment.

Main Methods:

• Review of existing literature on cancer lipogenesis and FASN inhibition.
• Analysis of clinical trial data for selective FASN inhibitors.
• Discussion of orlistat's mechanism of action and off-target effects.

Main Results:

• Selective FASN inhibitors have shown disease stabilization as the sole response in clinical trials.
• The efficacy of complete FASN inhibition in eliciting antitumor responses remains under investigation.
• Orlistat, a FASN inhibitor, exhibits off-target actions on at least seven targets relevant to tumor biology.

Conclusions:

• Targeting cancer's lipogenic phenotype via FASN inhibition is a viable therapeutic strategy.
• Orlistat's promiscuity as a drug may offer therapeutic advantages, warranting further investigation.
• Development of intravenous orlistat formulations is crucial for evaluating its therapeutic potential and the concept of drug promiscuity in cancer therapy.