Validation of the use of a fluorescent PARP1 inhibitor for the detection of oral, oropharyngeal and oesophageal epithelial cancers

For oral, oropharyngeal and oesophageal cancer, the early detection of tumours and of residual tumour after surgery are prognostic factors of recurrence rates and patient survival. Here, we report the validation, in animal models and a human, of the use of a previously described fluorescently labell...

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Bibliographic Details
Published in:	Nature biomedical engineering Vol. 4; no. 3; pp. 272 - 285
Main Authors:	Kossatz, Susanne, Pirovano, Giacomo, Demétrio De Souza França, Paula, Strome, Arianna L., Sunny, Sumsum P., Zanoni, Daniella Karassawa, Mauguen, Audrey, Carney, Brandon, Brand, Christian, Shah, Veer, Ramanajinappa, Ravindra D., Hedne, Naveen, Birur, Praveen, Sihag, Smita, Ghossein, Ronald A., Gönen, Mithat, Strome, Marshall, Suresh, Amritha, Molena, Daniela, Ganly, Ian, Kuriakose, Moni A., Patel, Snehal G., Reiner, Thomas
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01.03.2020 Nature Publishing Group
Subjects:	13/106 13/31 13/51 14/19 14/34 59/78 631/67/1536 639/166/985 64/60 692/53/2421 Animal models Animals Biomarkers, Tumor - isolation & purification Biomarkers, Tumor - metabolism Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Cancer Contrast agents Deoxyribonucleic acid Disease Models, Animal DNA DNA repair Enzymes Esophageal Neoplasms - diagnostic imaging Esophageal Neoplasms - pathology Esophagus Female Fluorescence Heterografts - diagnostic imaging Human tissues Humans Inhibitors Intestine Male Medical prognosis Mice Mouthwashes Oral carcinoma Oral cavity Oropharyngeal Neoplasms - diagnostic imaging Oropharyngeal Neoplasms - pathology Pharynx Poly (ADP-Ribose) Polymerase-1 - drug effects Poly (ADP-Ribose) Polymerase-1 - isolation & purification Poly (ADP-Ribose) Polymerase-1 - metabolism Poly(ADP-ribose) Polymerase 1 Poly(ADP-ribose) Polymerase Inhibitors - pharmacology Ribose Surgery Swine Tumors
ISSN:	2157-846X, 2157-846X
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Summary:	For oral, oropharyngeal and oesophageal cancer, the early detection of tumours and of residual tumour after surgery are prognostic factors of recurrence rates and patient survival. Here, we report the validation, in animal models and a human, of the use of a previously described fluorescently labelled small-molecule inhibitor of the DNA repair enzyme poly(ADP–ribose) polymerase 1 (PARP1) for the detection of cancers of the oral cavity, pharynx and oesophagus. We show that the fluorescent contrast agent can be used to quantify the expression levels of PARP1 and to detect oral, oropharyngeal and oesophageal tumours in mice, pigs and fresh human biospecimens when delivered topically or intravenously. The fluorescent PARP1 inhibitor can also detect oral carcinoma in a patient when applied as a mouthwash, and discriminate between fresh biopsied samples of the oral tumour and the surgical resection margin with more than 95% sensitivity and specificity. The PARP1 inhibitor could serve as the basis of a rapid and sensitive assay for the early detection and for the surgical-margin assessment of epithelial cancers of the upper intestinal tract. A fluorescently labelled inhibitor of the DNA repair enzyme poly(ADP–ribose) polymerase 1 is used to detect epithelial cancers of the upper intestinal tract in animals, in biopsied human tissue and in a human patient.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Author contributions: S.K., G.P., M.A.K., S.P., and T.R. conceived the study and designed the experiments. S.K., G.P., A.L.S., S.P.S., P.D.S.F., D.K.Z., C.B., R.G. V.S., P.B., N.H., R.D.R., A.S., and T.R. carried out the experiments and collected and analysed the data. S.K., S.P.S., P.D.S.F., D.K.Z., A.S., S.P., and T.R. wrote IRB protocols. A.M., M.G., G.P., and S.K. conducted statistical analysis of the data. M.S. and M.A.K. contributed experimental or analysis tools. S.K. and T.R. wrote the manuscript. All authors carefully reviewed and approved the manuscript.
ISSN:	2157-846X 2157-846X
DOI:	10.1038/s41551-020-0526-9