An overview of cancer multidrug resistance: a still unsolved problem

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Multidrug resistance (MDR) remains a significant challenge in cancer treatment.
• Novel targeted therapies are often ineffective due to similar resistance mechanisms as traditional chemotherapy.
• Classical MDR mechanisms include enhanced transporter activity, altered cell death pathways, and target molecule modifications.

Purpose of the Study:

• To review the persistent problem of anticancer multidrug resistance (MDR).
• To highlight that classical MDR mechanisms also confer resistance to novel targeted agents.
• To discuss the limitations of current high-throughput technologies in addressing MDR.

Main Methods:

• Literature review of established and emerging mechanisms of anticancer drug resistance.
• Analysis of the impact of classical MDR mechanisms on both conventional and targeted therapies.
• Evaluation of the utility of high-throughput "-omics" technologies in the context of MDR.

Main Results:

• Classical MDR mechanisms, such as enhanced drug efflux pumps (e.g., ABC transporters) and altered cell death pathways, are implicated in resistance to both traditional and targeted anticancer drugs.
• Despite advancements in '-omics' technologies, no significant breakthroughs have been made in developing predictive diagnostic assays or novel chemosensitizers.
• The complex interplay of molecular mechanisms results in an individual MDR phenotype that remains difficult to overcome.

Conclusions:

• Anticancer drug resistance is a complex, multifaceted problem that is not resolved by targeted therapies alone.
• Existing MDR mechanisms pose a significant barrier to effective cancer treatment, impacting both old and new drugs.
• Current '-omics' approaches have not yet translated into clinically useful tools for overcoming MDR or personalizing cancer therapy.