Pirfenidone normalizes the tumor microenvironment to improve chemotherapy

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Tumor microenvironment normalization is a strategy to improve cancer therapy.
• Targeting the extracellular matrix can decompress tumor vasculature, enhancing drug delivery.
• There is a need for safe pharmaceutical agents to remodel solid tumor microenvironments.

Purpose of the Study:

• To investigate the potential of repurposing Pirfenidone for tumor microenvironment normalization.
• To assess Pirfenidone's effects on extracellular matrix components and tumor vasculature.
• To evaluate if Pirfenidone enhances chemotherapy efficacy.

Main Methods:

• Two orthotopic mammary tumor models were used.
• Pirfenidone's effects on collagen, hyaluronan, and TGFβ signaling pathway were analyzed.
• Vessel functionality, perfusion, and anti-tumor efficacy of doxorubicin were measured.

Main Results:

• Pirfenidone significantly reduced collagen and hyaluronan levels in tumors.
• Pirfenidone treatment increased blood vessel functionality and perfusion.
• Pirfenidone enhanced the anti-tumor efficacy of doxorubicin.
• Reduced extracellular matrix components were linked to TGFβ signaling pathway inhibition.

Conclusions:

• Pirfenidone effectively normalizes the tumor microenvironment by remodeling the extracellular matrix.
• Repurposing Pirfenidone shows promise for improving drug delivery and cancer therapy efficacy.
• Pirfenidone's mechanism involves inhibiting the TGFβ signaling pathway.