Ambrisentan, an endothelin receptor type A-selective antagonist, inhibits cancer cell migration, invasion, and...

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• The endothelin type A receptor (ETAR) plays a crucial role in tumor progression and metastasis.
• Existing treatments for cancer metastasis have limitations, necessitating novel therapeutic strategies.

Purpose of the Study:

• To investigate the anti-tumor effects of Ambrisentan, an FDA-approved ETAR antagonist, in vitro and in vivo.
• To explore Ambrisentan's potential as a novel therapeutic agent for treating cancer metastasis.

Main Methods:

• In vitro studies assessed the effects of Ambrisentan on tumor cell migration and invasion.
• Whole transcriptome analysis (RNAseq) was performed on tumor cells treated with Ambrisentan.
• A preclinical murine model of metastatic breast cancer was used to evaluate Ambrisentan's in vivo efficacy.

Main Results:

• Ambrisentan significantly inhibited the migration and invasion of various cancer cell lines (pancreatic, ovarian, breast, leukemia).
• RNAseq analysis revealed that Ambrisentan modulated the transcriptome of tumor cells, tending to normalize gene expression profiles.
• In vivo, Ambrisentan treatment reduced lung and liver metastasis in a breast cancer model and enhanced animal survival.

Conclusions:

• Ambrisentan demonstrates significant anti-metastatic properties in both in vitro and in vivo cancer models.
• The findings suggest a novel therapeutic application for Ambrisentan in managing and treating cancer metastasis.
• Targeting ETAR with Ambrisentan represents a promising strategy for improving outcomes in metastatic cancer patients.