Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age

Folate receptor alpha (FRα) has long been the focus of therapeutics development in oncology across several solid tumors, notably ovarian, lung, and subsets of breast cancers. Its multiple roles in cellular metabolism and carcinogenesis and tumor-specific overexpression relative to normal tissues ren...

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Main Authors: Yi Liu, Xinyi Chen, Theodore Evan, Benjamina Esapa, Alicia Chenoweth, Anthony Cheung, Sophia N Karagiannis
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:mAbs
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19420862.2025.2470309
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author Yi Liu
Xinyi Chen
Theodore Evan
Benjamina Esapa
Alicia Chenoweth
Anthony Cheung
Sophia N Karagiannis
author_facet Yi Liu
Xinyi Chen
Theodore Evan
Benjamina Esapa
Alicia Chenoweth
Anthony Cheung
Sophia N Karagiannis
author_sort Yi Liu
collection DOAJ
description Folate receptor alpha (FRα) has long been the focus of therapeutics development in oncology across several solid tumors, notably ovarian, lung, and subsets of breast cancers. Its multiple roles in cellular metabolism and carcinogenesis and tumor-specific overexpression relative to normal tissues render FRα an attractive target for biological therapies. Here we review the biological significance, expression distribution, and characteristics of FRα as a highly promising and now established therapy target. We discuss the ongoing development of FRα-targeting antibodies and antibody-drug conjugates (ADCs), the first of which has been approved for the treatment of ovarian cancer, providing the impetus for heightened research and therapy development. Novel insights into the tumor microenvironment, advances in antibody engineering to enhance immune-mediated effects, the emergence of ADCs, and several studies of anti-FRα agents combined with chemotherapy, targeted and immune therapy are offering new perspectives and treatment possibilities. Hence, we highlight key translational research and discuss several preclinical studies and clinical trials of interest, with an emphasis on agents and therapy combinations with potential to change future clinical practice.
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1942-0870
language English
publishDate 2025-12-01
publisher Taylor & Francis Group
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series mAbs
spelling doaj-art-bf38177be26e4e829b445afbb6beccde2025-08-20T03:21:39ZengTaylor & Francis GroupmAbs1942-08621942-08702025-12-0117110.1080/19420862.2025.2470309Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of ageYi Liu0Xinyi Chen1Theodore Evan2Benjamina Esapa3Alicia Chenoweth4Anthony Cheung5Sophia N Karagiannis6St. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s Hospital, London, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s Hospital, London, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s Hospital, London, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s Hospital, London, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s Hospital, London, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s Hospital, London, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s Hospital, London, UKFolate receptor alpha (FRα) has long been the focus of therapeutics development in oncology across several solid tumors, notably ovarian, lung, and subsets of breast cancers. Its multiple roles in cellular metabolism and carcinogenesis and tumor-specific overexpression relative to normal tissues render FRα an attractive target for biological therapies. Here we review the biological significance, expression distribution, and characteristics of FRα as a highly promising and now established therapy target. We discuss the ongoing development of FRα-targeting antibodies and antibody-drug conjugates (ADCs), the first of which has been approved for the treatment of ovarian cancer, providing the impetus for heightened research and therapy development. Novel insights into the tumor microenvironment, advances in antibody engineering to enhance immune-mediated effects, the emergence of ADCs, and several studies of anti-FRα agents combined with chemotherapy, targeted and immune therapy are offering new perspectives and treatment possibilities. Hence, we highlight key translational research and discuss several preclinical studies and clinical trials of interest, with an emphasis on agents and therapy combinations with potential to change future clinical practice.https://www.tandfonline.com/doi/10.1080/19420862.2025.2470309ADCantibodyfolate receptor alphaFRαoncologytargeted therapy
spellingShingle Yi Liu
Xinyi Chen
Theodore Evan
Benjamina Esapa
Alicia Chenoweth
Anthony Cheung
Sophia N Karagiannis
Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age
mAbs
ADC
antibody
folate receptor alpha
FRα
oncology
targeted therapy
title Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age
title_full Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age
title_fullStr Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age
title_full_unstemmed Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age
title_short Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age
title_sort folate receptor alpha for cancer therapy an antibody and antibody drug conjugate target coming of age
topic ADC
antibody
folate receptor alpha
FRα
oncology
targeted therapy
url https://www.tandfonline.com/doi/10.1080/19420862.2025.2470309
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