Multidrug resistance in cancer: current understandings and future perspective

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Multidrug resistance (MDR) is a major obstacle to successful cancer treatment.
• MDR is now understood as a dynamic, adaptive survival strategy of heterogeneous tumors under therapy.
• This complex phenotype involves intertwined survival networks within tumor cells and their microenvironment.

Purpose of the Study:

• To systematically review the evolution and mechanisms of MDR.
• To assess current challenges in overcoming drug resistance in various cancers.
• To explore novel strategies for reversing MDR and advancing precision cancer therapy.

Main Methods:

• Comprehensive literature review of MDR mechanisms.
• Analysis of cell-intrinsic resistance pathways (e.g., drug redistribution, apoptosis evasion).
• Summary of tumor microenvironment (TME)-mediated resistance (e.g., stromal barriers, immunosuppression).

Main Results:

• MDR involves both cell-autonomous mechanisms and TME-mediated factors.
• Current therapies face significant resistance challenges, leading to clinical failures.
• Novel strategies include nanotechnology, omics analysis, and AI for precision interventions.

Conclusions:

• A paradigm shift from single-target interventions to multidimensional ecological remodeling is necessary.
• Future research should focus on personalized, closed-loop precision therapy frameworks.
• Dynamic monitoring and multi-target synergistic interventions are key to overcoming MDR.