A study published in Engineering reports on Mar. 10 that targeting the protein IGF2BP2 could enhance the effectiveness of anti-angiogenic therapies for colorectal cancer. The research was conducted by an international team from Sun Yat-sen University and The Chinese University of Hong Kong.
Colorectal cancer is a major cause of illness and death worldwide, with more than 20% of cases diagnosed at an advanced stage and a five-year survival rate of only 14%. Angiogenesis, or the formation of new blood vessels, plays a key role in tumor growth and spread. While drugs like bevacizumab and regorafenib are used to block angiogenesis, their impact is often limited due to rapid development of drug resistance.
The researchers analyzed data from several sources and found that IGF2BP2 was consistently increased in colorectal cancer tissues with high levels of angiogenesis. Further tests confirmed that higher IGF2BP2 expression was linked to worse outcomes for patients, suggesting it could serve as a biomarker for disease progression.
Laboratory experiments showed that reducing IGF2BP2 in cancer cells lowered their ability to promote blood vessel growth, while increasing IGF2BP2 had the opposite effect. In animal models, mice engineered to have more IGF2BP2 developed tumors faster due to increased angiogenesis, while those lacking the protein had slower tumor growth and healthier blood vessels.
The study also explained how IGF2BP2 works: it binds to CEMIP mRNA modified by m⁶A, stabilizing it and boosting its secretion. This secreted protein then interacts with GRP78 on endothelial cells, triggering signals that lead to abnormal blood vessel growth. Importantly, blocking IGF2BP2—either genetically or with drugs—combined with existing anti-angiogenic treatments led to greater tumor suppression in multiple models.
Researchers say these findings point toward new strategies for overcoming resistance to current therapies by focusing on the m⁶A-CEMIP-GRP78 pathway regulated by IGF2BP2. Future studies may further explore this approach in clinical settings.
