Targeting colorectal cancer liver metastasis through repurposing metabolic and immune inhibitors: A theoretical study

Area of Science:

• Oncology
• Computational Biology
• Pharmacology

Background:

• Colorectal cancer liver metastasis (CRLM) is a leading cause of cancer death.
• Current treatments for advanced CRLM face challenges due to complexity and poor prognosis.
• Novel therapeutic strategies are urgently needed for CRLM.

Purpose of the Study:

• To computationally identify potential drug repurposing candidates for CRLM.
• To analyze key signaling pathways involved in CRLM.
• To evaluate single and combination therapies for CRLM treatment.

Main Methods:

• Utilized a Boolean Network model for computational analysis.
• Investigated signaling pathways including WNT, PI3K/AKT/mTOR, MAPK, Hedgehog, TGF-β, NF-kB, NOTCH, and HGF.
• Evaluated metabolic and immune inhibitors for CRLM treatment, including single and multi-agent scenarios.

Main Results:

• Highlighted the efficacy of metabolic inhibitors such as Simvastatin and Metformin for CRLM.
• Predicted compatible partner drugs to enhance the efficacy of metabolic inhibitors.
• Identified Pembrolizumab as a potential immunotherapy drug for improving CRLM treatment.

Conclusions:

• Computational drug repurposing offers a viable strategy for improving CRLM treatment outcomes.
• Simvastatin and Metformin show potential as core components of novel CRLM therapeutic combinations.
• Further experimental validation is required for the proposed drug combinations.