Drug resistance, the last frontier?

Area of Science:

• Biochemistry
• Pharmacology
• Molecular Biology

Background:

• Multidrug resistance (MDR) is a significant challenge in medicine, limiting the efficacy of various therapies.
• P-glycoprotein (P-gp) is a key efflux pump implicated in MDR, actively transporting drugs out of cells.
• Understanding P-gp function is crucial for developing strategies to circumvent drug resistance.

Purpose of the Study:

• To present the state-of-the-art knowledge on multidrug resistance and P-glycoprotein function as of 1990.
• To discuss the potential of modulating P-gp activity using specific pharmacological agents.
• To explore the role of calcium channel blockers and antiestrogens in manipulating P-gp function.

Main Methods:

• Review of existing scientific literature and research findings up to 1990.
• Analysis of the biochemical and functional properties of P-glycoprotein.
• Discussion of experimental data on the interaction of calcium channel blockers and antiestrogens with P-gp.

Main Results:

• P-glycoprotein acts as an energy-dependent efflux pump contributing to multidrug resistance.
• Certain calcium channel blockers demonstrate the ability to inhibit P-gp-mediated drug efflux.
• Antiestrogens also show potential in modifying P-glycoprotein function and overcoming resistance.

Conclusions:

• Modulation of P-glycoprotein offers a promising avenue for overcoming multidrug resistance.
• Calcium channel blockers and antiestrogens represent potential therapeutic agents for MDR reversal.
• Further research into P-gp inhibitors is warranted to enhance treatment outcomes.