Monocarboxylate transporter 1 and 4 inhibitors as potential therapeutics for treating solid tumours: A review with...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Multidrug resistance (MDR) is a primary cause of chemotherapy and radiotherapy failure in cancer.
• Monocarboxylate transporters (MCTs) MCT1 and MCT4 are overexpressed in solid tumors, supporting cancer cell survival and proliferation by regulating lactate transport and pH balance.
• Inhibiting MCTs presents a promising therapeutic strategy against drug-resistant cancers.

Purpose of the Study:

• To review recent advancements in identifying effective inhibitors for MCT1 and/or MCT4.
• To explore the potential of these inhibitors as anticancer therapies for overcoming MDR.
• To propose structure-activity relationships for various compound classes to guide future research.

Main Methods:

• Literature review of recent developments in MCT1 and MCT4 inhibitor research.
• Analysis of structure-activity relationships for different classes of MCT inhibitors.
• Synthesis of current understanding to highlight target importance.

Main Results:

• Several small molecule inhibitors for MCT1 (e.g., AZD3965, AR-C155858) show clinical potential.
• Fewer MCT4 inhibitors are documented, with some featuring pyrazole and indazole scaffolds.
• Ongoing research focuses on developing selective and potent inhibitors for both MCT1 and MCT4.

Conclusions:

• MCT1 and MCT4 are critical targets for overcoming MDR in solid tumors.
• Further development of selective, potent, and safe MCT1/MCT4 inhibitors is crucial for advancing cancer chemotherapy.
• Understanding structure-activity relationships will accelerate the discovery of novel anticancer agents targeting these transporters.