Metal- and metalloid-based compounds to target and reverse cancer multidrug resistance

Area of Science:

• Medicinal Chemistry
• Oncology
• Pharmacology

Background:

• Drug resistance is a primary reason for cancer treatment failure, especially in advanced stages.
• Metal and metalloid compounds offer unique chemical properties for designing drugs to overcome cancer drug resistance.
• Platinum-based drugs are crucial in cancer therapy, necessitating strategies to reverse resistance to them and multidrug resistance (MDR).

Purpose of the Study:

• To provide an overview of drug design strategies for reversing platinum drug resistance and MDR.
• To review metal and metalloid compounds demonstrating drug resistance reversal activity.
• To identify open research questions and future directions in the field of metal-based cancer therapeutics.

Main Methods:

• Literature review of metal (platinum, ruthenium, iridium, gold, copper) and metalloid (arsenic, selenium) compounds.
• Analysis of drug resistance mechanisms including altered protein expression, ABC transporter efflux, metabolism, redox homeostasis, DNA repair, apoptosis, and immune interaction.
• Focus on compounds exhibiting collateral sensitivity in cancer cells overexpressing ABC transporters.

Main Results:

• Identified metal and metalloid compounds with demonstrated drug resistance reversal activity.
• Highlighted specific mechanisms of resistance targeted by these compounds.
• Emphasized compounds with collateral sensitivity as a promising strategy for ABC transporter-overexpressing cancers.

Conclusions:

• Metal and metalloid compounds represent a versatile platform for developing novel anti-cancer drugs to combat resistance.
• Collateral sensitivity offers a targeted approach to treat cancers with high ABC transporter expression.
• Further research is needed to elucidate the precise mechanisms of action for potent resistance-reversing compounds.