Apelin inhibition prevents resistance and metastasis associated with anti-angiogenic therapy

Area of Science:

• Oncology
• Cancer Biology
• Vascular Biology

Background:

• Angiogenesis, the formation of new blood vessels, is crucial for tumor growth and metastasis.
• Anti-angiogenic therapies face limitations due to therapy-induced resistance, often leading to tumor progression.
• Overcoming this resistance is critical for improving cancer treatment efficacy.

Purpose of the Study:

• To investigate the role of Apelin in tumor angiogenesis and resistance to anti-angiogenic therapies.
• To determine if Apelin inhibition can overcome resistance and improve treatment outcomes in preclinical cancer models.
• To identify Apelin as a potential therapeutic target for enhancing anti-angiogenic treatment.

Main Methods:

• Preclinical studies using mammary and lung cancer models.
• Inhibition of Apelin signaling pathways.
• Assessment of tumor growth, angiogenesis, hypoxia, and metastasis.
• Analysis of tumor microenvironment components, including myeloid-derived suppressor cells.
• Correlation of Apelin levels with patient prognosis in anti-angiogenic therapy.

Main Results:

• Apelin inhibition effectively reduced tumor growth and angiogenesis.
• Targeting Apelin improved vessel function and decreased myeloid-derived suppressor cell infiltration.
• Apelin blockage prevented resistance to receptor tyrosine kinase (RTK) inhibitor therapy in lung and breast cancer models.
• Apelin inhibition reduced metastases and did not increase tumor hypoxia.
• High Apelin levels correlated with poor prognosis in patients receiving anti-angiogenic therapy.

Conclusions:

• Apelin is a druggable target that can reduce tumor blood vessel density and normalize vasculature.
• Inhibition of Apelin overcomes resistance to anti-angiogenic therapies, reducing tumor growth and metastasis.
• Targeting Apelin represents a promising strategy to enhance the efficacy of anti-angiogenic treatments in cancer therapy.