Blood Vessel-Targeted Therapy in Colorectal Cancer: Current Strategies and Future Perspectives

Area of Science:

• Oncology
• Vascular Biology
• Cancer Therapeutics

Background:

• The tumor vasculature is a critical component of the tumor microenvironment and a target for anti-cancer therapies.
• Antiangiogenic treatments for colorectal carcinoma (CRC) have been available for two decades, yet response predictors and resistance remain significant clinical challenges.
• Pathological tumor vasculature in CRC exhibits heterogeneity, impaired barrier function, and immunosuppressive properties, complicating standard therapeutic approaches.

Purpose of the Study:

• To review the historical context and current strategies for antiangiogenic therapy in CRC.
• To discuss the challenges posed by vascular heterogeneity, plasticity, and resistance in CRC treatment.
• To explore novel therapeutic opportunities including vascular normalization and targeting angiocrine proteins.

Main Methods:

• Review of existing literature on antiangiogenic therapies in colorectal carcinoma.
• Analysis of vascular heterogeneity, plasticity, and functional characteristics in the CRC microenvironment.
• Identification and discussion of emerging therapeutic targets, including angiocrine proteins and vascular normalization strategies.

Main Results:

• Despite prolonged use, antiangiogenic therapy for CRC lacks reliable response predictors and faces considerable treatment resistance.
• Tumor vascular characteristics, such as heterogeneous perfusion and impaired barrier function, contribute to therapeutic challenges.
• Angiocrine proteins, released by vascular cells, have emerged as key regulators of tumor progression and potential therapeutic targets.

Conclusions:

• Addressing vascular heterogeneity and plasticity is crucial for improving antiangiogenic therapy efficacy in CRC.
• Targeting angiocrine proteins and promoting vascular normalization represent promising avenues for developing patient-tailored CRC treatments.
• Future research should focus on leveraging these novel strategies to overcome treatment resistance and enhance therapeutic outcomes in colorectal carcinoma.