Targeting autophagy in dysfunctional tumor vasculature.

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Tumor vasculature is crucial for cancer progression and therapeutic resistance.
• Autophagy is a key regulator of endothelial cell function within tumors.
• Understanding vascular autophagy is vital for developing novel cancer therapies.

Purpose of the Study:

• To review current knowledge on autophagy in tumor vasculature.
• To examine molecular mechanisms, cellular interactions, and therapeutic applications of vascular autophagy.
• To highlight challenges and future directions for clinical translation.

Main Methods:

• Literature review synthesizing current research on autophagy and tumor vasculature.
• Analysis of molecular pathways regulating autophagy in tumor endothelial cells (TECs).
• Examination of stromal cell interactions and immune system interplay with vascular autophagy.

Main Results:

• Autophagy in TECs is modulated by mTOR/AMPK signaling, VEGF, and stress responses.
• Stromal cells (pericytes, proteoglycans) influence vascular autophagy through direct and paracrine signaling.
• Combined therapies (autophagy inhibitors + anti-angiogenics/ICIs/chemotherapy) show preclinical promise.

Conclusions:

• Vascular autophagy plays a dual role, supporting tumor survival and creating vulnerabilities.
• Clinical translation requires TEC-specific modulators, biomarkers, and optimized strategies.
• Targeting vascular autophagy offers a potential strategy to overcome therapeutic resistance in cancer.