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The way to precision medicine in gynecologic cancers: The first case report of an exceptional response to alpelisib in a PIK3CA-mutated endometrial cancer

Endometrial cancer (EC) is the most common gynecologic cancer in Europe and its prevalence is increasing. EC includes a biological and clinical heterogeneous group of tumors, usually classified as type I (endometrioid) or type II (non-endometrioid) based on the histopathological characteristics. In...

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Autores principales: Passarelli, Anna, Ventriglia, Jole, Pisano, Carmela, Cecere, Sabrina Chiara, Napoli, Marilena Di, Rossetti, Sabrina, Tambaro, Rosa, Tarotto, Luca, Fiore, Francesco, Farolfi, Alberto, Bartoletti, Michele, Pignata, Sandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880853/
https://www.ncbi.nlm.nih.gov/pubmed/36713525
http://dx.doi.org/10.3389/fonc.2022.1088962
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author Passarelli, Anna
Ventriglia, Jole
Pisano, Carmela
Cecere, Sabrina Chiara
Napoli, Marilena Di
Rossetti, Sabrina
Tambaro, Rosa
Tarotto, Luca
Fiore, Francesco
Farolfi, Alberto
Bartoletti, Michele
Pignata, Sandro
author_facet Passarelli, Anna
Ventriglia, Jole
Pisano, Carmela
Cecere, Sabrina Chiara
Napoli, Marilena Di
Rossetti, Sabrina
Tambaro, Rosa
Tarotto, Luca
Fiore, Francesco
Farolfi, Alberto
Bartoletti, Michele
Pignata, Sandro
author_sort Passarelli, Anna
collection PubMed
description Endometrial cancer (EC) is the most common gynecologic cancer in Europe and its prevalence is increasing. EC includes a biological and clinical heterogeneous group of tumors, usually classified as type I (endometrioid) or type II (non-endometrioid) based on the histopathological characteristics. In 2013, a new molecular classification was proposed by The Cancer Genome Atlas (TCGA) based on the comprehensive molecular profiling of EC. Several molecular somatic alterations have been described in development and progression of EC. Using these molecular features, EC was reclassified into four subgroups: POLE ultra-mutated, MSI hypermutated, copy-number low, and copy-number high that correlate with the prognosis. To this regard, it is widely reported that EC has more frequent mutations in the phosphatidylinositol 3-kinase (PI3K) pathway signaling than any other tumor. PIK3CA is the main significant mutated gene after PTEN alterations. Overall, over 90% of endometrioid tumors have activating PI3K molecular alterations that suggests its critical role in the EC pathogenesis. Thus, the dysregulation of PI3K pathway represents an attractive target in EC treatment. Herein, we report a radiological and clinically meaningful response to a selective PIK3 inhibitor in a patient with extensively pre-treated advanced endometrioid EC harboring a somatic activating PIK3CA hotspot mutation. These evidences provide the rational for translational strategies of the PI3K inhibition and could support the clinical usefulness of PIK3CA genotyping in advanced EC. To our knowledge, this is the first clinical case of PIK3CA-mutated EC successfully treated with alpelisib.
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spelling pubmed-98808532023-01-28 The way to precision medicine in gynecologic cancers: The first case report of an exceptional response to alpelisib in a PIK3CA-mutated endometrial cancer Passarelli, Anna Ventriglia, Jole Pisano, Carmela Cecere, Sabrina Chiara Napoli, Marilena Di Rossetti, Sabrina Tambaro, Rosa Tarotto, Luca Fiore, Francesco Farolfi, Alberto Bartoletti, Michele Pignata, Sandro Front Oncol Oncology Endometrial cancer (EC) is the most common gynecologic cancer in Europe and its prevalence is increasing. EC includes a biological and clinical heterogeneous group of tumors, usually classified as type I (endometrioid) or type II (non-endometrioid) based on the histopathological characteristics. In 2013, a new molecular classification was proposed by The Cancer Genome Atlas (TCGA) based on the comprehensive molecular profiling of EC. Several molecular somatic alterations have been described in development and progression of EC. Using these molecular features, EC was reclassified into four subgroups: POLE ultra-mutated, MSI hypermutated, copy-number low, and copy-number high that correlate with the prognosis. To this regard, it is widely reported that EC has more frequent mutations in the phosphatidylinositol 3-kinase (PI3K) pathway signaling than any other tumor. PIK3CA is the main significant mutated gene after PTEN alterations. Overall, over 90% of endometrioid tumors have activating PI3K molecular alterations that suggests its critical role in the EC pathogenesis. Thus, the dysregulation of PI3K pathway represents an attractive target in EC treatment. Herein, we report a radiological and clinically meaningful response to a selective PIK3 inhibitor in a patient with extensively pre-treated advanced endometrioid EC harboring a somatic activating PIK3CA hotspot mutation. These evidences provide the rational for translational strategies of the PI3K inhibition and could support the clinical usefulness of PIK3CA genotyping in advanced EC. To our knowledge, this is the first clinical case of PIK3CA-mutated EC successfully treated with alpelisib. Frontiers Media S.A. 2023-01-13 /pmc/articles/PMC9880853/ /pubmed/36713525 http://dx.doi.org/10.3389/fonc.2022.1088962 Text en Copyright © 2023 Passarelli, Ventriglia, Pisano, Cecere, Napoli, Rossetti, Tambaro, Tarotto, Fiore, Farolfi, Bartoletti and Pignata https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Passarelli, Anna
Ventriglia, Jole
Pisano, Carmela
Cecere, Sabrina Chiara
Napoli, Marilena Di
Rossetti, Sabrina
Tambaro, Rosa
Tarotto, Luca
Fiore, Francesco
Farolfi, Alberto
Bartoletti, Michele
Pignata, Sandro
The way to precision medicine in gynecologic cancers: The first case report of an exceptional response to alpelisib in a PIK3CA-mutated endometrial cancer
title The way to precision medicine in gynecologic cancers: The first case report of an exceptional response to alpelisib in a PIK3CA-mutated endometrial cancer
title_full The way to precision medicine in gynecologic cancers: The first case report of an exceptional response to alpelisib in a PIK3CA-mutated endometrial cancer
title_fullStr The way to precision medicine in gynecologic cancers: The first case report of an exceptional response to alpelisib in a PIK3CA-mutated endometrial cancer
title_full_unstemmed The way to precision medicine in gynecologic cancers: The first case report of an exceptional response to alpelisib in a PIK3CA-mutated endometrial cancer
title_short The way to precision medicine in gynecologic cancers: The first case report of an exceptional response to alpelisib in a PIK3CA-mutated endometrial cancer
title_sort way to precision medicine in gynecologic cancers: the first case report of an exceptional response to alpelisib in a pik3ca-mutated endometrial cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880853/
https://www.ncbi.nlm.nih.gov/pubmed/36713525
http://dx.doi.org/10.3389/fonc.2022.1088962
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