Rita Azevedo1, Janine Soares2, Andreia Peixoto3, Sofia Cotton2, Luís Lima4, Lúcio Lara Santos5, José Alexandre Ferreira6. 1. Experimental Pathology and Therapeutics Group, Research Centre, Portuguese Oncology Institute of Porto (IPO-Porto), R. Dr. António Bernardino de Almeida 62, 4200-162 Porto, Portugal; Institute of Biomedical Sciences Abel Salazar, University of Porto, R. Jorge de Viterbo Ferreira 228, 4050-013 Porto, Portugal. 2. Experimental Pathology and Therapeutics Group, Research Centre, Portuguese Oncology Institute of Porto (IPO-Porto), R. Dr. António Bernardino de Almeida 62, 4200-162 Porto, Portugal. 3. Experimental Pathology and Therapeutics Group, Research Centre, Portuguese Oncology Institute of Porto (IPO-Porto), R. Dr. António Bernardino de Almeida 62, 4200-162 Porto, Portugal; Institute of Biomedical Sciences Abel Salazar, University of Porto, R. Jorge de Viterbo Ferreira 228, 4050-013 Porto, Portugal; Institute for Research and Innovation in Health (i3S), University of Porto, R. Alfredo Allen, 4200-135 Porto, Portugal. 4. Experimental Pathology and Therapeutics Group, Research Centre, Portuguese Oncology Institute of Porto (IPO-Porto), R. Dr. António Bernardino de Almeida 62, 4200-162 Porto, Portugal; Institute for Research and Innovation in Health (i3S), University of Porto, R. Alfredo Allen, 4200-135 Porto, Portugal; Glycobiology in Cancer, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), R. Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal; Porto Comprehensive Cancer Centre (P.ccc), R. Dr. António Bernardino de Almeida 62, 4200-162 Porto, Portugal. 5. Experimental Pathology and Therapeutics Group, Research Centre, Portuguese Oncology Institute of Porto (IPO-Porto), R. Dr. António Bernardino de Almeida 62, 4200-162 Porto, Portugal; Institute of Biomedical Sciences Abel Salazar, University of Porto, R. Jorge de Viterbo Ferreira 228, 4050-013 Porto, Portugal; Health School of University Fernando Pessoa, Praça de 9 de Abril 349, 4249-004 Porto, Portugal; Department of Surgical Oncology, Portuguese Institute of Oncology (IPO-Porto), R. Dr. António Bernardino de Almeida 62, 4200-162 Porto, Portugal. 6. Experimental Pathology and Therapeutics Group, Research Centre, Portuguese Oncology Institute of Porto (IPO-Porto), R. Dr. António Bernardino de Almeida 62, 4200-162 Porto, Portugal; Institute of Biomedical Sciences Abel Salazar, University of Porto, R. Jorge de Viterbo Ferreira 228, 4050-013 Porto, Portugal; Institute for Research and Innovation in Health (i3S), University of Porto, R. Alfredo Allen, 4200-135 Porto, Portugal; Glycobiology in Cancer, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), R. Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal; Porto Comprehensive Cancer Centre (P.ccc), R. Dr. António Bernardino de Almeida 62, 4200-162 Porto, Portugal; International Iberian Nanotechnology Laboratory (INL), Avda. Mestre José Veiga, 4715 Braga, Portugal. Electronic address: jose.a.ferreira@ipoporto.min-saude.pt.
Abstract
CONTEXT: Circulating tumor cells (CTC) in peripheral blood of cancer patients provide an opportunity for real-time liquid biopsies capable of aiding early intervention, therapeutic decision, response to therapy, and prognostication. Nevertheless, the rare and potentially heterogeneous molecular nature of CTC has delayed the standardization of robust high-throughput capture/enrichment and characterization technologies. OBJECTIVE: This review aims to systematize emerging solutions for CTC analysis in bladder cancer (BC), their opportunities and limitations, while providing key insights on specific technologic aspects that may ultimately guide molecular studies and clinical implementation. EVIDENCE ACQUISITION: State-of-the-art screening for CTC technologies and clinical applications in BC was conducted in MEDLINE through PubMed. EVIDENCE SYNTHESIS: From 200 records identified by the search query, 25 original studies and 1 meta-analysis met the full criteria for selection. A significant myriad of CTC technological platforms, including immunoaffinity, biophysical, and direct CTC detection by molecular methods have been presented. Despite their preliminary nature and irrespective of the applied technology, most studies concluded that CTC counts in peripheral blood correlated with metastasis. Associations with advanced tumor stage and grade and worst prognosis have been suggested. However, the unspecific nature, low sensitivity, and the lack of standardization of current methods still constitutes a major drawback. Moreover, few comprehensive molecular studies have been conducted on these poorly known class of malignant cells. CONCLUSION: The current rationale supports the importance of moving the CTC field beyond proof of concept studies toward molecular-based solutions capable of improving disease management. The road has been paved for identification of highly specific CTC biomarkers and novel targeted approaches, foreseeing successful clinical applications.
CONTEXT: Circulating tumor cells (CTC) in peripheral blood of cancerpatients provide an opportunity for real-time liquid biopsies capable of aiding early intervention, therapeutic decision, response to therapy, and prognostication. Nevertheless, the rare and potentially heterogeneous molecular nature of CTC has delayed the standardization of robust high-throughput capture/enrichment and characterization technologies. OBJECTIVE: This review aims to systematize emerging solutions for CTC analysis in bladder cancer (BC), their opportunities and limitations, while providing key insights on specific technologic aspects that may ultimately guide molecular studies and clinical implementation. EVIDENCE ACQUISITION: State-of-the-art screening for CTC technologies and clinical applications in BC was conducted in MEDLINE through PubMed. EVIDENCE SYNTHESIS: From 200 records identified by the search query, 25 original studies and 1 meta-analysis met the full criteria for selection. A significant myriad of CTC technological platforms, including immunoaffinity, biophysical, and direct CTC detection by molecular methods have been presented. Despite their preliminary nature and irrespective of the applied technology, most studies concluded that CTC counts in peripheral blood correlated with metastasis. Associations with advanced tumor stage and grade and worst prognosis have been suggested. However, the unspecific nature, low sensitivity, and the lack of standardization of current methods still constitutes a major drawback. Moreover, few comprehensive molecular studies have been conducted on these poorly known class of malignant cells. CONCLUSION: The current rationale supports the importance of moving the CTC field beyond proof of concept studies toward molecular-based solutions capable of improving disease management. The road has been paved for identification of highly specific CTC biomarkers and novel targeted approaches, foreseeing successful clinical applications.
Authors: Oliver Hommerding; Yves Allory; Pedram Argani; Tarek A Bismar; Lukas Bubendorf; Sofía Canete-Portillo; Alcides Chaux; Ying-Bei Chen; Liang Cheng; Antonio L Cubilla; Lars Egevad; Anthony J Gill; David J Grignon; Arndt Hartmann; Ondrej Hes; Muhammad T Idrees; Chia-Sui Kao; Margaret A Knowles; Leendert H J Looijenga; Tamara L Lotan; Colin C Pritchard; Mark A Rubin; Scott A Tomlins; Theodorus H Van der Kwast; Elsa F Velazquez; Joshua I Warrick; Sean R Williamson; Glen Kristiansen Journal: Pathologe Date: 2021-01-04 Impact factor: 1.011