Targeting angiogenesis in gastrointestinal tumors: strategies from vascular disruption to vascular normalization and promotion strategies angiogenesis strategies in GI tumor therapy

Abstract

Angiogenesis plays a critical role in the progression of gastrointestinal (GI) tumors, making it an important therapeutic target. This review explores recent advancements in targeting angiogenesis for GI tumor therapy, highlighting strategies that range from vascular disruption to vascular promotion. The biological foundation of tumor angiogenesis is discussed, with a focus on the molecular mechanisms that regulate this process, including key players such as VEGF, HIFs, and non-coding RNAs. Current therapeutic strategies, including anti-angiogenic agents, vascular normalization approaches, and emerging vascular promotion therapies, are analyzed for their clinical applications and limitations. Additionally, the review examines combination strategies that integrate anti-angiogenic therapy with chemotherapy, immunotherapy, and other modalities to enhance efficacy and overcome resistance. Despite significant progress, challenges such as drug resistance, tumor heterogeneity, and adverse effects remain. Future research directions emphasize the discovery of novel molecular targets, development of personalized treatments, and innovative combination therapies to optimize outcomes for patients with GI tumors. This comprehensive review provides a foundation for advancing angiogenesis-targeted therapies in GI cancer treatment.

Keywords: angiogenesis; clinical applications; gastrointestinal tumors; molecular mechanisms; therapeutic strategies; vessel disruption.

Figure 1

The role of angiogenesis in tumor growth, invasion and metastasis. Rapid tumor expansion leads to reduced oxygen supply, and the resulting tumor microenvironment stimulates excessive angiogenesis by increasing various pro-angiogenic factors, including VEGF, PDGF, FGF, and angiopoietin. Subsequently, the neovascularization facilitates the transport of oxygen and nutrients, further supporting the survival, growth and proliferation of tumor cells. As tumor cells develop a more aggressive phenotype, they continue to proliferate, spread and induce angiogenesis, and tumor cells invade and metastasize through the blood circulation to distant tissues.

Figure 2

Angiogenesis in hypoxic cancer microenvironment of gastrointestinal tumors. HIF-1α stabilizes and promotes transcription of VEGF, MMPs and other factors under hypoxic conditions, increases vascular permeability and promotes abnormal formation of tumor vessels.

Figure 3

Combining anti-angiogenic therapies with other treatment modalities, such as chemotherapy, immunotherapy, and targeted therapies, in gastrointestinal cancer.