Natural-Origin Compounds as Future Precision Partners in Combination Cancer Therapy

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Cancer multidrug resistance (MDR) is often mediated by ATP-binding cassette (ABC) transporters.
• ABC transporter activity links to Nrf2-driven antioxidant defense, lowering the oxidative threshold in MDR cancer cells.

Purpose of the Study:

• To explore the potential of natural or nature-inspired compounds in overcoming MDR.
• To investigate how these compounds can induce collateral sensitivity (CS) by modulating redox balance and ABC transporter activity.

Main Methods:

• Investigating natural compounds for their ability to inhibit efflux, modulate redox balance, and evade immune responses.
• Addressing challenges in characterization and preclinical validation of these compounds.

Main Results:

• Natural compounds can target the vulnerability of MDR cancer cells by simultaneously modulating redox balance and ABC transporters.
• These compounds offer a multi-target therapeutic strategy combining efflux inhibition, redox modulation, and immune evasion.

Conclusions:

• Natural-origin compounds show promise for treating MDR cancers through a multi-targeted approach.
• Further research and adaptive trial designs are needed to overcome challenges like bioavailability and tumor heterogeneity for clinical translation.