The potential of using circulating tumour cells and their gene expression to predict docetaxel response in metastatic prostate cancer.

Autor:	Davies CR; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Guo T; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.; Department of Cell Biology and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Burke E; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Stankiewicz E; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.; Central Biobank, Medical University of Gdansk, Gdansk, Poland., Xu L; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China., Mao X; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Scandura G; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Rajan P; Centre for Cancer Cell and Molecular Biology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.; Department of Urology, Barts Health National Health Service Trust (NHS), London, United Kingdom.; Division of Surgery and Interventional Sciences, University College London, London, United Kingdom.; University College London Hospitals, National Health Service (NHS) Foundation Trust, London, United Kingdom., Tipples K; Department of Urology, Barts Health National Health Service Trust (NHS), London, United Kingdom., Alifrangis C; University College London Hospitals, National Health Service (NHS) Foundation Trust, London, United Kingdom.; Department of Medical Oncology, Barts Health National Health Service (NHS) Trust, London, United Kingdom., Wimalasingham AG; Department of Medical Oncology, Barts Health National Health Service (NHS) Trust, London, United Kingdom., Galazi M; Department of Medical Oncology, Barts Health National Health Service (NHS) Trust, London, United Kingdom., Crusz S; Department of Medical Oncology, Barts Health National Health Service (NHS) Trust, London, United Kingdom., Powles T; Department of Urology, Barts Health National Health Service Trust (NHS), London, United Kingdom.; Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Grey A; Department of Urology, Barts Health National Health Service Trust (NHS), London, United Kingdom.; Division of Surgery and Interventional Sciences, University College London, London, United Kingdom.; University College London Hospitals, National Health Service (NHS) Foundation Trust, London, United Kingdom., Oliver T; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Kudahetti S; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Shaw G; Department of Urology, Barts Health National Health Service Trust (NHS), London, United Kingdom.; Division of Surgery and Interventional Sciences, University College London, London, United Kingdom.; University College London Hospitals, National Health Service (NHS) Foundation Trust, London, United Kingdom., Berney D; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Shamash J; Department of Medical Oncology, Barts Health National Health Service (NHS) Trust, London, United Kingdom., Lu YJ; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2023 Jan 16; Vol. 12, pp. 1060864. Date of Electronic Publication: 2023 Jan 16 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.1060864
Abstrakt:	Background: Docetaxel improves overall survival (OS) in castration-resistant prostate cancer (PCa) (CRPC) and metastatic hormone-sensitive PCa (mHSPC). However, not all patients respond due to inherent and/or acquired resistance. There remains an unmet clinical need for a robust predictive test to stratify patients for treatment. Liquid biopsy of circulating tumour cell (CTCs) is minimally invasive, can provide real-time information of the heterogeneous tumour and therefore may be a potentially ideal docetaxel response prediction biomarker. Objective: In this study we investigate the potential of using CTCs and their gene expression to predict post-docetaxel tumour response, OS and progression free survival (PFS). Methods: Peripheral blood was sampled from 18 mCRPC and 43 mHSPC patients, pre-docetaxel treatment, for CTC investigation. CTCs were isolated using the epitope independent Parsortix ® system and gene expression was determined by multiplex RT-qPCR. We evaluated CTC measurements for post-docetaxel outcome prediction using receiver operating characteristics and Kaplan Meier analysis. Results: Detection of CTCs pre-docetaxel was associated with poor patient outcome post-docetaxel treatment. Combining total-CTC number with PSA and ALP predicted lack of partial response (PR) with an AUC of 0.90, p= 0.037 in mCRPC. A significantly shorter median OS was seen in mCRPC patients with positive CTC-score (12.80 vs. 37.33 months, HR= 5.08, p= 0.0005), ≥3 total-CTCs/7.5mL (12.80 vs. 37.33 months, HR= 3.84, p= 0.0053), ≥1 epithelial-CTCs/7.5mL (14.30 vs. 37.33 months, HR= 3.89, p= 0.0041) or epithelial to mesenchymal transitioning (EMTing)-CTCs/7.5mL (11.32 vs. 32.37 months, HR= 6.73, p= 0.0001). Significantly shorter PFS was observed in patients with ≥2 epithelial-CTCs/7.5mL (7.52 vs. 18.83 months, HR= 3.93, p= 0.0058). mHSPC patients with ≥5 CTCs/7.5mL had significantly shorter median OS (24.57 vs undefined months, HR= 4.14, p= 0.0097). In mHSPC patients, expression of KLK2 , KLK4 , ADAMTS1 , ZEB1 and SNAI1 was significantly associated with shorter OS and/or PFS. Importantly, combining CTC measurements with clinical biomarkers increased sensitivity and specificity for prediction of patient outcome. Conclusion: While it is clear that CTC numbers and gene expression were prognostic for PCa post-docetaxel treatment, and CTC subtype analysis may have additional value, their potential predictive value for docetaxel chemotherapy response needs to be further investigated in large patient cohorts. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Davies, Guo, Burke, Stankiewicz, Xu, Mao, Scandura, Rajan, Tipples, Alifrangis, Wimalasingham, Galazi, Crusz, Powles, Grey, Oliver, Kudahetti, Shaw, Berney, Shamash and Lu.)
Databáze:	MEDLINE
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