Repurposing dimethyl fumarate for cancer therapy: current evidence and future directions

Area of Science:

• Pharmacology and Oncology
• Drug Repurposing
• Molecular Mechanisms of Cancer

Background:

• Dimethyl fumarate (DMF) is an FDA-approved medication for multiple sclerosis, known to modulate the NF-κB pathway.
• Emerging research highlights DMF's potential anticancer properties, including direct cytotoxicity and synergistic effects with other chemotherapeutics.
• DMF's mechanisms of action extend beyond NF-κB inhibition to include Nrf2 stimulation, anti-inflammation, epigenetic modulation, and regulation of epithelial-mesenchymal transition (EMT).

Purpose of the Study:

• To review existing anticancer studies of Dimethyl fumarate (DMF) as a single agent and in combination regimens.
• To explore the potential of DMF as a repurposed drug for cancer treatment, particularly in chemo-resistant cases.

Main Methods:

• Review of in vitro and in vivo studies investigating the anticancer effects of Dimethyl fumarate (DMF).
• Analysis of molecular mechanisms underlying DMF's cytotoxic and chemosensitizing activities.
• Examination of DMF's covalent binding to protein thiol groups.

Main Results:

• Dimethyl fumarate (DMF) exhibits anticancer effects across various cancer cell types.
• DMF demonstrates synergy with conventional and targeted chemotherapies, enhancing efficacy in resistant cancer cells.
• DMF acts as a chemotherapy agent by inhibiting NF-κB, stimulating Nrf2, suppressing inflammation, and modulating epigenetic modifications and EMT.

Conclusions:

• Dimethyl fumarate (DMF) is a promising candidate for cancer therapy, especially for chemo-resistant patients.
• DMF's ability to sensitize cancer cells to other agents, coupled with its existing FDA approval, supports its potential for expedited clinical application.
• Further research into DMF's anticancer applications could offer new therapeutic avenues for patients with limited treatment options.