Sun Yat-sen University Breakthrough: IGF2BP2 as Anti-Angiogenic Colorectal Cancer Therapy Enhancer

Colorectal cancer (CRC), one of the most prevalent malignancies worldwide, poses a significant health challenge in China, where incidence rates continue to climb amid rapid urbanization and dietary shifts. Recent groundbreaking research from leading Chinese institutions has pinpointed a novel target to revolutionize anti-angiogenic therapies, offering hope for improved outcomes in advanced cases. This study, published in the prestigious Engineering journal from Tsinghua University Press, uncovers how insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) drives tumor angiogenesis, providing a pathway to enhance existing treatments like bevacizumab.

Understanding this mechanism could transform CRC management, particularly as resistance to anti-angiogenic drugs remains a major hurdle. Researchers at Sun Yat-sen University (SYSU) and collaborators have demonstrated that blocking IGF2BP2 not only curbs vessel formation but synergizes with standard therapies to shrink tumors more effectively in preclinical models.

🌡️ The Growing Burden of Colorectal Cancer in China

China faces an escalating colorectal cancer crisis, with new cases surpassing 600,000 annually by recent estimates, making it the fourth leading cause of cancer-related deaths. Age-standardized incidence rates (ASIR) have risen steadily, projected to continue upward through 2036 due to aging populations, Westernized diets high in processed meats, and screening gaps in rural areas. In 2022 alone, CRC contributed to over 300,000 deaths, with five-year survival for advanced stages hovering around 14%.

Urban centers like Guangzhou and Beijing report higher prevalence, linked to lifestyle factors. Early-onset CRC (under 50) is surging, with incidence expected to peak soon. National screening programs have boosted detection, but advanced diagnoses dominate, underscoring the need for innovative therapies.

• Annual new cases: ~607,900 (2019), rising 474% since 1990.
• Mortality ASMR: ~15-20 per 100,000, higher in males.
• Prevalence: Over 3.6 million living with CRC (2021).

Sun Yat-sen University Cancer Center, a hub for CRC research, leads efforts to address this through precision medicine.Explore research positions at top Chinese cancer centers.

Challenges in Current Anti-Angiogenic Therapies for CRC

Anti-angiogenic therapies inhibit vascular endothelial growth factor (VEGF), starving tumors of blood supply. Bevacizumab (Avastin), approved for metastatic CRC, extends survival by months when combined with chemotherapy. Regorafenib and fruquintinib (Chinese-developed) offer later-line options, with FRESCO-2 trial showing benefits in refractory cases.

However, rapid resistance—within months—limits efficacy. Mechanisms include alternative angiogenesis pathways, vessel normalization evasion, and tumor microenvironment adaptations. In China, where mCRC comprises 20% of diagnoses, overcoming resistance is critical. Clinical trials like NCT02748772 test Endostar (recombinant endostatin) combinations, reflecting local innovation.

Researchers note stromal fibrosis and immune evasion exacerbate issues, prompting epitranscriptomic targets like m⁶A modifications.

Sun Yat-sen University's Pioneering Study on IGF2BP2

Led by Jun Yu and team at SYSU's State Key Laboratory of Oncology in South China, the study identifies IGF2BP2 as upregulated in hypervascular CRC, correlating with poor prognosis. Published in Engineering (Impact Factor ~9.6), it leverages multi-omics to reveal IGF2BP2's role.

Co-authors from The Chinese University of Hong Kong analyzed TCGA data, confirming enrichment in high-angiogenesis tumors. SYSU's expertise in CRC cohorts enabled robust validation.

This reflects China's rising research output, with SYSU ranking top in oncology publications.

Decoding the IGF2BP2-CEMIP Pathway Step-by-Step

IGF2BP2, an N⁶-methyladenosine (m⁶A) reader protein, binds m⁶A-modified CEMIP (cell migration-inducing and hyaluronan-binding protein) mRNA in CRC cells. This stabilizes CEMIP transcripts, boosting translation and secretion.

1. CRC cells upregulate IGF2BP2 under hypoxic stress.
2. IGF2BP2 recognizes m⁶A on CEMIP mRNA, preventing degradation.
3. Secreted CEMIP binds GRP78 (glucose-regulated protein 78) on endothelial cells.
4. GRP78 activates PI3K/AKT/ERK signaling, promoting proliferation, migration, and leaky vessels.

This "epitranscriptomic axis" fosters abnormal vasculature, fueling metastasis.

Experimental Evidence: From Cells to Mouse Models

In vitro, IGF2BP2 knockdown in CRC cell lines reduced endothelial tube formation and migration. Overexpression heightened pro-angiogenic effects.

In vivo, intestine-specific IGF2BP2 knockout mice showed normalized vessels and slowed AOM/DSS-induced CRC. Knock-in accelerated progression via leaky vasculature.

Synergy tests: IGF2BP2 inhibitors (CWI1-2), siRNA-loaded LNPs, or KO combined with bevacizumab/regorafenib slashed tumor volumes 70-90% in xenografts.

SYSU's advanced models mimic human CRC heterogeneity.

Therapeutic Potential and Synergy Strategies

Targeting IGF2BP2 addresses resistance by pruning dysfunctional vessels, improving drug delivery. Chemical inhibitor CWI1-2 offers oral potential; LNPs enable tumor-specific delivery.

In China, where fruquintinib thrives, IGF2BP2 combos could extend PFS. No ongoing trials yet, but preclinical promise warrants Phase I.

Stakeholders: Oncologists praise multi-modal approaches; patients seek less toxic options.

• Benefits: Enhanced efficacy, reduced resistance.
• Risks: Off-target m⁶A effects; monitor liver function.

Implications for Chinese Higher Education and Research Ecosystem

SYSU exemplifies China's oncology leadership, with Sun Yat-sen University Cancer Center hosting national cohorts. Collaborations with HKCU bolster translational research.

Funding from NSFC drives such innovations. Universities like Peking Union Medical College complement with clinical trials.

This positions China as a global CRC research hub, attracting talent.

Future Outlook: Clinical Translation and Precision Oncology

Biomarkers like IGF2BP2 expression could stratify patients. AI integration for m⁶A prediction accelerates discovery.

China's 14th Five-Year Plan emphasizes oncology; expect trials by 2028. Global partnerships vital.

Actionable: Advocate screening; researchers, pursue academic CV tips for grants.

Photo by Jerry Zhang on Unsplash

Conclusion: A New Era for CRC Treatment in China

SYSU's IGF2BP2 discovery heralds enhanced anti-angiogenic strategies, tackling China's CRC epidemic. For careers, explore higher-ed jobs, rate professors, or university positions in oncology. Stay informed via career advice.