Patients with metastatic uroepithelial carcinoma of the bladder who have failed first-line chemotherapy cannot benefit from lapatinib There has long been a lack of effective treatment strategies for metastatic uroepithelial carcinoma of the bladder after failure of first-line chemotherapy with cisplatin-based agents. Paclitaxel, vincristine, oxaliplatin, albumin-coated paclitaxel, and pazopanib have all been tried for second-line treatment, but all have shown poor efficacy. The search for new therapeutic targets for urothelial carcinoma of the bladder is imminent. Human epidermal-growth-factor receptor 1 and 2 (HER1 and HER2) are highly expressed in many tumors, and they are not only closely related to tumorigenesis and progression, but also potential therapeutic targets. A high percentage of bladder cancer overexpression of HER1 or HER2 has been previously reported, and overexpression of HER1 or HER2 is significantly associated with poor patient prognosis. The ensuing question is: Can bladder cancer patients benefit from drug therapy acting on HER1 and HER2 targets? The 4505 study reported at this annual meeting found that patients with metastatic bladder uroepithelial cancer who failed first-line chemotherapy and had HER1 or HER2 overexpression in their tumor tissue did not benefit from treatment with lapatinib (HER1 and HER2 inhibitors). Further subgroup analysis revealed that even patients with strong positive expression of HER1 or HER2 (++++) did not benefit from lapatinib treatment. Therefore, in the current era of precision medicine, we need to further use genomic and proteomic technologies to analyze, identify and validate new therapeutic targets for uroepithelial carcinoma of the bladder.