TY - JOUR
T1 - Folate receptor alpha for cancer therapy
T2 - an antibody and antibody-drug conjugate target coming of age
AU - Liu, Yi
AU - Chen, Sammy
AU - Evan, Theo
AU - Esapa, Benjamina
AU - Chenoweth, Alicia
AU - Cheung, Anthony
AU - Karagiannis, Sophia N
N1 - Publisher Copyright:
© 2025 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2025/3/6
Y1 - 2025/3/6
N2 - 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.
AB - 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.
KW - Humans
KW - Folate Receptor 1/antagonists & inhibitors
KW - Immunoconjugates/therapeutic use
KW - Neoplasms/drug therapy
KW - Animals
KW - Tumor Microenvironment/immunology
KW - Molecular Targeted Therapy/methods
KW - Female
UR - http://www.scopus.com/inward/record.url?scp=86000574548&partnerID=8YFLogxK
U2 - 10.1080/19420862.2025.2470309
DO - 10.1080/19420862.2025.2470309
M3 - Review article
C2 - 40045156
SN - 1942-0862
VL - 17
SP - 2470309
JO - Mabs
JF - Mabs
IS - 1
M1 - 2470309
ER -
