Folate Receptor Alpha Emerges as a Versatile Oncology Target and Predictive Biomarker
This review covers the exploitation of folate receptor alpha across multiple therapeutic platforms including antibody-drug conjugates, small-molecule drug conjugates, radioimmunoconjugates, and CAR-T cells, with late-phase trial data in ovarian, lung, and breast cancers. Beyond therapeutics, FRa serves as a predictive biomarker for patient selection and can be imaged radiologically or intraoperatively to improve surgical outcomes. The convergence of companion diagnostics with targeted therapy makes FRa one of the more clinically advanced biomarker-drug pairings in solid oncology.
The original study
Exploiting the folate receptor α in oncology.
- Authors
- Scaranti M, Cojocaru E, Banerjee S, Banerji U
- Journal
- Nature reviews. Clinical oncology
- Type
- Journal Article, Research Support, Non-U.S. Gov't, Review
- PMID
- 32152484
Original abstract
Folate receptor α (FRα) came into focus as an anticancer target many decades after the successful development of drugs targeting intracellular folate metabolism, such as methotrexate and pemetrexed. Binding to FRα is one of several methods by which folate is taken up by cells; however, this receptor is an attractive anticancer drug target owing to the overexpression of FRα in a range of solid tumours, including ovarian, lung and breast cancers. Furthermore, using FRα to better localize effective anticancer therapies to their target tumours using platforms such as antibody-drug conjugates, small-molecule drug conjugates, radioimmunoconjugates and, more recently, chimeric antigen receptor T cells could further improve the outcomes of patients with FRα-overexpressing cancers. FRα can also be harnessed for predictive biomarker research. Moreover, imaging FRα radiologically or in real time during surgery can lead to improved functional imaging and surgical outcomes, respectively. In this Review, we describe the current status of research into FRα in cancer, including data from several late-phase clinical trials involving FRα-targeted therapies, and the use of new technologies to develop FRα-targeted agents with improved therapeutic indices.