Concurrently, a recent study also revealed that inhibiting the highly expressed SERPINE1/PAI-1 in CAFs can reverse the stromal barrier and enhance chemotherapy sensitivity, thereby enabling effective intervention in the tumor microenvironment (73).These findings highlight the limitations of single-pathway blockade and underscore the need for refined patient stratification, targeted delivery systems, and rational combination regimens. The gene discussed is SERPINE1; the disease is neoplasm.