Folate receptor alpha (FRα)

Class

FRα-directed antibody-drug conjugate (sofetabart mipitecan)

Pathway

antibody binds folate receptor alpha, overexpressed in ovarian and other epithelial tumors, delivering a cytotoxic payload; being tested head-to-head against the approved FRα ADC mirvetuximab soravtansine

Folate receptor alpha (FRα) is a cell-surface protein that binds folate (vitamin B9) and helps pull it into cells through a process called endocytosis, in which the cell membrane engulfs the receptor along with whatever is attached to it. Most normal adult tissues carry little FRα, but it is markedly overexpressed on several epithelial cancers, most notably ovarian and endometrial carcinomas and some lung adenocarcinomas. This combination of restricted normal-tissue expression and reliable internalization makes FRα an appealing target for antibody-drug conjugates (ADCs): a monoclonal antibody that recognizes FRα is chemically linked to a potent cytotoxic payload. When the antibody binds the receptor, the whole complex is drawn inside the tumor cell, where the payload is released and interferes with cell division or DNA integrity, killing the cancer cell while limiting exposure of healthy tissue. This targeted-delivery strategy aims to concentrate cytotoxic activity specifically in FRα-high tumors rather than relying on systemic chemotherapy alone. It is broadly relevant to ovarian cancer treatment, where high-grade epithelial tumors frequently display elevated folate receptor expression, and reflects a wider effort in oncology to use receptor-directed conjugates as more selective alternatives to conventional cytotoxic regimens.