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Potential Targeted Therapies in Ovarian Cancer

Background: We aimed to identify somatic pathogenic and likely pathogenic mutations using next-generation sequencing (NGS). The mutational findings were held against clinically well-described data to identify potential targeted therapies in Danish patients diagnosed with high-grade serous ovarian ca...

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Autores principales: Sisman, Yagmur, Vestergaard, Lau Kræsing, de Oliveira, Douglas Nogueira Perez, Poulsen, Tim Svenstrup, Schnack, Tine Henrichsen, Høgdall, Claus, Høgdall, Estrid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697427/
https://www.ncbi.nlm.nih.gov/pubmed/36355495
http://dx.doi.org/10.3390/ph15111324
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author Sisman, Yagmur
Vestergaard, Lau Kræsing
de Oliveira, Douglas Nogueira Perez
Poulsen, Tim Svenstrup
Schnack, Tine Henrichsen
Høgdall, Claus
Høgdall, Estrid
author_facet Sisman, Yagmur
Vestergaard, Lau Kræsing
de Oliveira, Douglas Nogueira Perez
Poulsen, Tim Svenstrup
Schnack, Tine Henrichsen
Høgdall, Claus
Høgdall, Estrid
author_sort Sisman, Yagmur
collection PubMed
description Background: We aimed to identify somatic pathogenic and likely pathogenic mutations using next-generation sequencing (NGS). The mutational findings were held against clinically well-described data to identify potential targeted therapies in Danish patients diagnosed with high-grade serous ovarian cancer (HGSC). Methods: We characterized the mutational profile of 128 HGSC patients. Clinical data were obtained from the Danish Gynecological Database and tissue samples were collected through the Danish CancerBiobank. DNA was analyzed using NGS. Results: 47 (37%) patients were platinum-sensitive, 32 (25%) partially platinum-sensitive, 35 (27%) platinum-resistant, and three (2%) platinum-refractory, while 11 (9%) patients did not receive chemotherapy. Overall, 27 (21%) had known druggable targets. Twelve (26%) platinum-sensitive patients had druggable targets for PARP inhibitors: one for tyrosine kinase inhibitors and one for immunotherapy treatment. Eight (25%) partially platinum-sensitive patients had druggable targets: seven were eligible for PARP inhibitors and one was potentially eligible for alpesilib and hormone therapy. Seven (20%) platinum-resistant patients had druggable targets: six (86%) were potentially eligible for PARP inhibitors, one for immunotherapy, and one for erdafitinib. Conclusions: PARP inhibitors are the most frequent potential targeted therapy in HGSC. However, other targeted therapies remain relevant for investigation according to our mutational findings.
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spelling pubmed-96974272022-11-26 Potential Targeted Therapies in Ovarian Cancer Sisman, Yagmur Vestergaard, Lau Kræsing de Oliveira, Douglas Nogueira Perez Poulsen, Tim Svenstrup Schnack, Tine Henrichsen Høgdall, Claus Høgdall, Estrid Pharmaceuticals (Basel) Article Background: We aimed to identify somatic pathogenic and likely pathogenic mutations using next-generation sequencing (NGS). The mutational findings were held against clinically well-described data to identify potential targeted therapies in Danish patients diagnosed with high-grade serous ovarian cancer (HGSC). Methods: We characterized the mutational profile of 128 HGSC patients. Clinical data were obtained from the Danish Gynecological Database and tissue samples were collected through the Danish CancerBiobank. DNA was analyzed using NGS. Results: 47 (37%) patients were platinum-sensitive, 32 (25%) partially platinum-sensitive, 35 (27%) platinum-resistant, and three (2%) platinum-refractory, while 11 (9%) patients did not receive chemotherapy. Overall, 27 (21%) had known druggable targets. Twelve (26%) platinum-sensitive patients had druggable targets for PARP inhibitors: one for tyrosine kinase inhibitors and one for immunotherapy treatment. Eight (25%) partially platinum-sensitive patients had druggable targets: seven were eligible for PARP inhibitors and one was potentially eligible for alpesilib and hormone therapy. Seven (20%) platinum-resistant patients had druggable targets: six (86%) were potentially eligible for PARP inhibitors, one for immunotherapy, and one for erdafitinib. Conclusions: PARP inhibitors are the most frequent potential targeted therapy in HGSC. However, other targeted therapies remain relevant for investigation according to our mutational findings. MDPI 2022-10-26 /pmc/articles/PMC9697427/ /pubmed/36355495 http://dx.doi.org/10.3390/ph15111324 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sisman, Yagmur
Vestergaard, Lau Kræsing
de Oliveira, Douglas Nogueira Perez
Poulsen, Tim Svenstrup
Schnack, Tine Henrichsen
Høgdall, Claus
Høgdall, Estrid
Potential Targeted Therapies in Ovarian Cancer
title Potential Targeted Therapies in Ovarian Cancer
title_full Potential Targeted Therapies in Ovarian Cancer
title_fullStr Potential Targeted Therapies in Ovarian Cancer
title_full_unstemmed Potential Targeted Therapies in Ovarian Cancer
title_short Potential Targeted Therapies in Ovarian Cancer
title_sort potential targeted therapies in ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697427/
https://www.ncbi.nlm.nih.gov/pubmed/36355495
http://dx.doi.org/10.3390/ph15111324
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