Targeting folate receptor alpha for cancer treatment

Abstract

// Anthony Cheung 1,2,* , Heather J. Bax 1,3,* , Debra H. Josephs 1,3 , Kristina M. Ilieva 1,2 , Giulia Pellizzari 1 , James Opzoomer 1 , Jacinta Bloomfield 1 , Matthew Fittall 1,2 , Anita Grigoriadis 2 , Mariangela Figini 4 , Silvana Canevari 4 , James F. Spicer 3 , Andrew N. Tutt 2 and Sophia N. Karagiannis 1,2 1 St. John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King’s College London & NIHR Biomedical Research Centre at Guy’s and St. Thomas’ Hospitals and King’s College London, Guy’s Hospital, London, United Kingdom 2 Breast Cancer Now Research Unit, Faculty of Life Sciences and Medicine, Guy’s Hospital, King’s College London, London, United Kingdom 3 Division of Cancer Studies, Faculty of Life Sciences and Medicine, Guy’s Hospital, King’s College London, London, United Kingdom 4 Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy * These authors have contributed equally to this work Correspondence to: Sophia N. Karagiannis, email: // Keywords : folate receptor alpha, cancer, biomarker, monoclonal antibodies, immunotherapy Received : March 25, 2016 Accepted : May 19, 2016 Published : May 27, 2016 Abstract Promising targeted treatments and immunotherapy strategies in oncology and advancements in our understanding of molecular pathways that underpin cancer development have reignited interest in the tumor-associated antigen Folate Receptor alpha (FRα). FRα is a glycosylphosphatidylinositol (GPI)-anchored membrane protein. Its overexpression in tumors such as ovarian, breast and lung cancers, low and restricted distribution in normal tissues, alongside emerging insights into tumor-promoting functions and association of expression with patient prognosis, together render FRα an attractive therapeutic target. In this review, we summarize the role of FRα in cancer development, we consider FRα as a potential diagnostic and prognostic tool, and we discuss different targeted treatment approaches with a specific focus on monoclonal antibodies. Renewed attention to FRα may point to novel individualized treatment approaches to improve the clinical management of patient groups that do not adequately benefit from current conventional therapies.