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Folate receptor alpha in ovarian cancer tissue and patient serum is associated with disease burden and treatment outcomes

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Heather Bax, Jitesh Chauhan, Chara Stavraka, Aida Santaolalla, Gabriel Osborn, Atousa Khiabany, Melanie Grandits, Jacobo Lopez-Abente Muroz, Lais Cristina Gusmao Ferreira, Charleen Chan Wah Hak, Alexandra Robinson, Amy Pope, Natalie Woodman, Cristina Naceur-Lombardelli, Sadek Malas, Mano Nakamura, Jack E M Coumbe, Roman Laddach, Silvia Mele, Silvia Crescioli & 16 more Anna Black, Sara Lombardi, Silvana Canevari, Mariangela Figini, Ahmad Sayasneh, Sophia Tsoka, Kevin FitzGerald, Cheryl Gillett, Sarah Pinder, Mieke Van Hemelrijck, Rebecca Kristeleit, Sharmistha Ghosh, Ana Montes, James Spicer, Sophia N Karagiannis, Debra Josephs

Original languageEnglish
Article number
Number of pages12
JournalBritish Journal of Cancer
Early online date19 Nov 2022
Accepted/In press28 Sep 2022
E-pub ahead of print19 Nov 2022

Bibliographical note

Funding Information: The research was supported by Cancer Research UK (C30122/A11527; C30122/A15774); the Academy of Medical Sciences; National Institute for Health Research (NIHR, CL-2020-17-002); CRUK/NIHR in England/DoH for Scotland, Wales and Northern Ireland Experimental Cancer Medicine Centre (C10355/A15587); the Guy’s and St Thomas’s Foundation Trust Charity Melanoma Special Fund (573); the Rotary Foundation of Rotary International; Breast Cancer Now (147; KCL-BCN-Q3); the Cancer Research UK King’s Health Partners Centre at King’s College London (C604/A25135); and the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London (IS-BRC-1215-20006). The authors are solely responsible for study design, data collection, analysis, decision to publish, and preparation of the manuscript. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Publisher Copyright: © 2022, The Author(s).


  • Bax et al BJC 2022

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King's Authors


Background: Survival rates for ovarian cancer remain poor, and monitoring and prediction of therapeutic response may benefit from additional markers. Ovarian cancers frequently overexpress Folate Receptor alpha (FRα) and the soluble receptor (sFRα) is measurable in blood. Here we investigated sFRα as a potential biomarker.

Methods: We evaluated sFRα longitudinally, before and during neo-adjuvant, adjuvant and palliative therapies, and tumour FRα expression status by immunohistrochemistry. The impact of free FRα on the efficacy of anti-FRα treatments was evaluated by an antibody-dependent cellular cytotoxicity assay.

Results: Membrane and/or cytoplasmic FRα staining were observed in 52.7% tumours from 316 ovarian cancer patients with diverse histotypes. Circulating sFRα levels were significantly higher in patients, compared to healthy volunteers, specifically in patients sampled prior to neoadjuvant and palliative treatments. sFRα was associated with FRα cell membrane expression in the tumour. sFRα levels decreased alongside concurrent tumour burden in patients receiving standard therapies. High concentrations of sFRα partly reduced anti-FRα antibody tumour cell killing, an effect overcome by increased antibody doses.

Conclusions: sFRα may present a non-invasive marker for tumour FRα expression, with the potential for monitoring patient response to treatment. Larger, prospective studies should evaluate FRα for assessing disease burden and response to systemic treatments.

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