Progress on the HIF-1α/VEGF/VEGFR2 signal pathway in hepatic alveolar echinococcosis

Meng-zhao Xu ¹ Fei Ke ¹ Jin-Ping Chai ² Ji-De A ^3* Qing-Long Tan ^4*

• ¹ Graduate School of Qinghai University, Xining, China
• ² Department of Internal Medicine-Cardiovascular, Qinghai Provincial People's Hospital, Xining, Qinghai Province, China
• ³ Department of Hepatic Hydatidosis, Qinghai Provincial People's Hospital, Xining, Qinghai Province, China
• ⁴ Department of General Surgery, Qinghai Provincial People’s Hospital, Xining, Qinghai Province, China

Alveolar echinococcosis (AE), a lethal parasitic zoonosis mimicking malignant t umors, progresses via hepatic infiltration and metastatic spread, causing multior gan failure. Despite its clinical resemblance to cancer, molecular drivers of its aggressiveness remain poorly defined. Recent studies highlight perilesional angi ogenesis as pivotal for lesion invasiveness, mediated by VEGF-driven pathologi cal vascularization. VEGF not only fuels parasitic proliferation by creating nutri ent-rich microenvironments but also engages crosstalk with host-parasite interact ions, including immune evasion by Echinococcus multilocularis, germinal layer hyperplasia, and periparasitic inflammation.Targeting the HIF-1α/VEGF/VEGFR2 axis emerges as a promising therapeutic strategy. Mechanistically, VEGF/VEGF R2 blockade may simultaneously disrupt angiogenesis-dependent parasitic expans ion and survival pathways. Preclinical evidence shows that inhibiting HIF-1α (VEGF's upstream regulator) suppresses metacestode proliferation and tissue inv asion by starving lesions of vascular support while modulating immune-inflamm atory responses. This dual action addresses both parasitic resource acquisition a nd host defense subversion.This review synthesizes molecular insights into HIF-1α/VEGF-mediated pathogenesis with clinical observations, proposing anti-angio genic therapy as a rational adjunct to current treatments. By delineating VEGF' s role in sustaining parasitic metabolic demands and immune regulation, we un derscore the translational potential of pathway-specific inhibitors. Such approach es could mitigate limitations of conventional therapies (e.g., benzimidazoles), pa rticularly for advanced-stage AE with microvascular proliferation. Systematic an alysis of angiogenesis signaling networks advances our understanding of AE's " parasitic cancer" paradigm while guiding development of targeted interventions to improve patient outcomes.