Revisiting VEGF/VEGFR-2 signalling as an anticancer target and its inhibitor discovery: where are we and where should...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Angiogenesis is critical for tumor growth and metastasis, making it a key therapeutic target.
• The vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) signaling pathway is frequently dysregulated in various cancers.
• Inhibiting the VEGF/VEGFR-2 pathway is a proven strategy for anti-cancer therapy.

Purpose of the Study:

• To review small molecule inhibitors targeting the VEGF/VEGFR-2 pathway.
• To analyze the biological activity, clinical progress, and structure-activity relationships of these inhibitors.
• To provide insights into the development of novel anti-angiogenesis cancer treatments.

Main Methods:

• Literature review of studies on VEGF/VEGFR-2 inhibitors.
• Classification of inhibitors based on dominant molecular skeletons.
• Analysis of biological activity, clinical trial data, and structure-activity relationships.

Main Results:

• Development of diverse small molecule inhibitors targeting VEGF or VEGFR-2.
• Identification of selective VEGF inhibitors and multi-target VEGFR-2 inhibitors.
• Demonstration of anti-tumor effects through inhibition of angiogenesis.

Conclusions:

• Targeting the VEGF/VEGFR-2 pathway is an effective clinical strategy for cancer treatment.
• Understanding structure-activity relationships is crucial for designing potent and selective inhibitors.
• Continued research into small molecule inhibitors holds promise for advancing anti-angiogenesis therapy.