Metal-Based Combination Therapies in Cancer: Mechanistic Principles and Emerging Opportunities

Area of Science:

• Inorganic Chemistry
• Medicinal Chemistry
• Oncology

Background:

• Metal-based anticancer agents offer unique coordination versatility and redox activity.
• Platinum-based chemotherapy faces challenges like resistance, toxicity, and incomplete tumor control.
• Combination therapy is crucial for enhancing efficacy and mitigating resistance in cancer treatment.

Purpose of the Study:

• To review recent advances in metal-based anticancer combination therapies.
• To categorize combinations based on mechanistic perspectives: chemotherapy, immunotherapy, and multimodal strategies.
• To provide a foundation for designing next-generation metal-based combination therapies.

Main Methods:

• Categorization of metal-based agent combinations with distinct chemotherapeutics.
• Discussion of metallodrugs' immunomodulatory functions for combination with immune checkpoint blockade.
• Exploration of multimodal strategies involving energy-responsive metal-based systems.

Main Results:

• Combinations can reinforce DNA damage, promote apoptosis, disrupt redox homeostasis, and exploit metabolic vulnerabilities.
• Metallodrugs can induce immunogenic cell death and reprogram the tumor microenvironment.
• Metal-based systems can be integrated into photodynamic, photothermal, or sonodynamic therapies.

Conclusions:

• Metal-based combination therapies offer synergistic enhancement of antitumor efficacy.
• Combining metallodrugs with immunotherapy and multimodal strategies shows significant potential.
• These insights guide the rational design of improved metal-based cancer treatments.