Emerging Anti-Cancer and Repurposed Therapies for Overcoming Multidrug Resistance in Lung Cancer

Area of Science:

• Oncology
• Pharmacology
• Biomedical Engineering

Background:

• Multidrug resistance (MDR) is a major challenge in lung cancer treatment, leading to poor clinical outcomes.
• MDR involves complex mechanisms including drug efflux, altered metabolism, DNA repair, and apoptosis inhibition.
• Tumor microenvironment, epigenetics, cancer stem cells, and intratumoral heterogeneity exacerbate MDR, making it adaptive and multifactorial.

Purpose of the Study:

• To outline emerging therapeutic strategies for overcoming MDR in lung cancer.
• To highlight the dual approach of targeted agents and drug repurposing.
• To discuss advanced monitoring and delivery systems for personalized treatment.

Main Methods:

• Utilizing next-generation tyrosine kinase inhibitors (TKIs), KRAS12C inhibitors, and bispecific antibodies to counter oncogene-driven resistance.
• Repurposing established drugs (e.g., statins, disulfiram, chloroquine) to target metabolic vulnerabilities and enhance chemosensitization.
• Employing liquid biopsies for real-time resistance monitoring and artificial intelligence (AI) for personalized combination therapy design.

Main Results:

• Targeted agents inhibit key signaling pathways promoting proliferation and resistance.
• Repurposed drugs modulate autophagy, mitochondrial bioenergetics, and redox homeostasis, acting as chemosensitizers.
• Liquid biopsies and AI-driven models enable patient stratification and rational combination therapy selection.

Conclusions:

• A combination of novel targeted therapies, repurposed drugs, advanced monitoring, and personalized delivery systems offers a flexible approach to conquer MDR in lung cancer.
• These integrated strategies aim to mitigate oxidative stress, immune evasion, and systemic toxicity.
• Personalized, combination therapies hold promise for improving efficacy and overcoming adaptive drug resistance in lung cancer patients.