Combination of vascular surgery with novel vascular targeting agents as cancer therapeutics

Area of Science:

• Oncology
• Vascular Biology
• Surgical Oncology

Background:

• Locally advanced solid tumors involving major vasculature pose significant surgical challenges.
• Oncovascular Surgery (OVS) aims for complete resection but can trigger systemic pro-angiogenic responses, promoting tumor recurrence.
• Vascular Targeting Agents (VTAs), including Anti-Angiogenic Agents (AIAs) and Vascular Disrupting Agents (VDAs), offer pharmacological strategies to control tumor vasculature.

Purpose of the Study:

• To review the mechanisms of VTAs and the consequences of OVS.
• To evaluate the biological interactions between OVS and VTAs.
• To propose a unified translational strategy for synergistic combination regimens.

Main Methods:

• Synthesis of molecular mechanisms of VTA function and selectivity.
• Detailed review of the technical aspects and systemic effects of OVS.
• Critical evaluation of the biological interface, including resistance mechanisms and post-surgical angiogenic response.

Main Results:

• OVS necessitates extensive resection but induces a pro-angiogenic surge, potentially enhancing tumor recurrence and metastasis.
• VTAs modulate tumor vasculature through distinct mechanisms (inhibition of growth or disruption of existing vessels).
• The integration of OVS and VTAs presents challenges in timing and toxicity management.

Conclusions:

• A synergistic approach combining OVS with precisely timed VTA administration is crucial for optimizing oncological outcomes.
• Understanding and managing the post-surgical angiogenic surge is key to preventing recurrence.
• Further research is needed to establish robust translational strategies for combined OVS-VTA therapies.