Folate Receptor Alpha (FRα/FOLR1) in Cancer: Diagnostic, Prognostic or Predictive Biomarker? A Critical Review of Its Clinical Utility

Folate receptor alpha (FRα) plays a key role in folate homeostasis. Folate is involved, among other processes, in nucleotide biosynthesis, and the marked difference between FRα expression in certain cancers and under physiological conditions gives this receptor potential as a cancer biomarker. However, the current state of knowledge points to a specific role for this marker and defines its potential place in cancer diagnosis and treatment. This review aims to critically evaluate the available evidence regarding the clinical utility of FRα. Analysis of the literature indicates that despite differences in expression, the sensitivity and specificity of FRα are insufficient for its use as a standalone diagnostic marker. In contrast, its potential as a prognostic marker is strongly dependent on cancer type. The strongest evidence of clinical utility concerns membranous FRα protein expression assessed by a validated immunohistochemical companion diagnostic assay for selecting patients with platinum-resistant ovarian cancer for mirvetuximab soravtansine treatment. In contrast, the predictive relevance of FRα for other targeted therapeutic strategies remains under investigation. Overall, FRα should be regarded as a clinically actionable biomarker in a defined therapeutic setting and as a promising, but not universally validated, diagnostic, prognostic, and predictive candidate in other oncological applications.