Sortilin-related receptor is a druggable therapeutic target in breast cancer

Area of Science:

• Oncology
• Molecular Biology
• Immunotherapy

Background:

• HER2-targeted therapies are crucial for breast cancer treatment but face challenges due to therapy resistance.
• Sortilin-related receptor (SorLA) has been identified as a key regulator of HER2/HER3 signaling, contributing to treatment resistance.

Purpose of the Study:

• To evaluate the therapeutic potential of targeting SorLA with a monoclonal antibody (SorLA ab) in HER2-positive breast cancer.
• To assess the efficacy of SorLA ab, alone and in combination with trastuzumab, in overcoming resistance mechanisms.

Main Methods:

• In vitro and in vivo studies using breast cancer cell lines and a mouse xenograft model.
• Assessment of SorLA ab's effect on cancer cell resistance to trastuzumab.
• Evaluation of combination therapy with SorLA ab and trastuzumab on tumor growth and density.
• Testing SorLA ab in patient-derived explant three-dimensional cultures.

Main Results:

• SorLA ab demonstrated an ability to alter breast cancer cell resistance to trastuzumab.
• Combination therapy of SorLA ab and trastuzumab significantly inhibited tumor cell proliferation and density in a preclinical model.
• SorLA ab effectively inhibited proliferation in patient-derived breast cancer explants.

Conclusions:

• SorLA is a druggable target in breast cancer, offering a novel therapeutic strategy.
• Targeting SorLA presents a promising approach to overcome resistance to existing HER2-targeted therapies.
• SorLA antibody therapy holds potential for improving clinical outcomes in HER2-positive breast cancer patients.