Drug Repurposing to Circumvent Immune Checkpoint Inhibitor Resistance in Cancer Immunotherapy

Area of Science:

• Oncology
• Immunotherapy
• Drug Discovery

Background:

• Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy but face significant challenges due to drug resistance.
• Drug resistance to ICI limits treatment efficacy and durable disease control for many cancer patients.
• Drug repurposing, applying existing drugs to new indications, is a viable strategy to address ICI resistance.

Purpose of the Study:

• To review current research on utilizing repurposed drugs to overcome resistance to immune checkpoint inhibitors (ICI).
• To explore mechanisms by which repurposed drugs enhance cancer immunotherapy.
• To highlight the role of biomarkers and advanced computational methods in identifying effective repurposed drugs.

Main Methods:

• Review of existing literature on drug repurposing for ICI resistance.
• Analysis of mechanisms including immunostimulatory activities and modulation of the tumor microenvironment (TME).
• Exploration of phenotypic screening, genomics, bioinformatics, artificial intelligence (AI), machine learning (ML), and deep learning (DL) for drug discovery.

Main Results:

• Repurposed drugs can overcome ICI resistance by either enhancing anti-tumor immunity or mitigating the immunosuppressive TME.
• Drug repurposing provides affordable and readily available treatment options compared to novel drug development.
• Biomarkers are crucial for patient stratification to maximize the benefits of repurposed drugs and combination therapies.

Conclusions:

• Drug repurposing is a powerful strategy to enhance the efficacy of immune checkpoint inhibitors (ICI) and combat cancer drug resistance.
• The combination of repurposed drugs with ICI offers novel therapeutic avenues.
• Advanced computational approaches and biomarker identification are key to realizing the full potential of drug repurposing in immuno-oncology.