The EphA2 tyrosine kinase receptor is highly expressed in several types of solid tumors.\nIn our recent studies, we targeted EphA2 in pancreatic cancer with agonistic agents and demonstrated\nthat suppression of EphA2 significantly reduced cancer-cell migration in cell-based assays. In the\npresent study, we focused on targeting EphA2 in prostate cancer. While not all prostate cancers\nexpress EphA2, we showed that enzalutamide induced EphA2 expression in prostate cancer cells\nand in a patient-derived xenograft (PDX) animal model, which provides further impetus to target\nEphA2 in prostate cancer. Western blot studies showed that agonistic dimeric synthetic (135H12)\nand natural (ephrinA1-Fc) ligands effectively degraded EphA2 receptor in the prostate cancer cell\nline PC-3. The agents also delayed cell migration of prostate cancer (PC-3) cells, while an in vivo\nPC-3 orthotopic metastatic nude-mouse model also revealed that administration of ephrinA1-Fc or\n135H12 strongly reduced metastases. The present study further validates EphA2 as an important\ntarget in metastatic prostate cancer treatment. Our results should incentivize further efforts aimed at\ndeveloping potent and effective EphA2 synthetic agonistic agents for the treatment of EphA2-driven\naggressive metastatic tumors including prostate, pancreatic, and breast cancer.
Loading....