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Progression and metastasis of small cell lung carcinoma: the role of the PI3K/Akt/mTOR pathway and metabolic alterations

Small cell lung carcinoma (SCLC) is characterized by high metastatic rate and poor prognosis. The platinum-based chemotherapy still represents the backbone of the therapy; however, acquired resistance develops almost in all patients. Although SCLC has been formerly considered a homogeneous disease,...

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Autores principales: Krencz, Ildiko, Sztankovics, Daniel, Danko, Titanilla, Sebestyen, Anna, Khoor, Andras
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825381/
https://www.ncbi.nlm.nih.gov/pubmed/34958428
http://dx.doi.org/10.1007/s10555-021-10012-4
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author Krencz, Ildiko
Sztankovics, Daniel
Danko, Titanilla
Sebestyen, Anna
Khoor, Andras
author_facet Krencz, Ildiko
Sztankovics, Daniel
Danko, Titanilla
Sebestyen, Anna
Khoor, Andras
author_sort Krencz, Ildiko
collection PubMed
description Small cell lung carcinoma (SCLC) is characterized by high metastatic rate and poor prognosis. The platinum-based chemotherapy still represents the backbone of the therapy; however, acquired resistance develops almost in all patients. Although SCLC has been formerly considered a homogeneous disease, recent advances in SCLC research have highlighted the importance of inter- and intratumoral heterogeneity and have resulted in the subclassification of SCLC. The newly described SCLC subtypes are characterized by distinct biological behavior and vulnerabilities that can be therapeutically exploited. The PI3K/Akt/mTOR pathway is frequently affected in SCLC, and its activation represents a promising therapeutic target. Since the mTOR pathway is a master regulator of cellular metabolism, its alterations may also influence the bioenergetic processes of SCLC cells. Despite the encouraging preclinical results, both mTOR and metabolic inhibitors have met limited clinical success so far. Patient selection for personalized therapy, the development of rational drug combinations, and a better understanding of heterogeneity and spatiotemporal evolution of the tumor cells may improve efficacy and can help to overcome acquired resistance. Here we provide a summary of current investigations regarding the role of the mTOR pathway and metabolic alterations in the progression and metastasis formation of SCLC.
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spelling pubmed-88253812022-02-23 Progression and metastasis of small cell lung carcinoma: the role of the PI3K/Akt/mTOR pathway and metabolic alterations Krencz, Ildiko Sztankovics, Daniel Danko, Titanilla Sebestyen, Anna Khoor, Andras Cancer Metastasis Rev Article Small cell lung carcinoma (SCLC) is characterized by high metastatic rate and poor prognosis. The platinum-based chemotherapy still represents the backbone of the therapy; however, acquired resistance develops almost in all patients. Although SCLC has been formerly considered a homogeneous disease, recent advances in SCLC research have highlighted the importance of inter- and intratumoral heterogeneity and have resulted in the subclassification of SCLC. The newly described SCLC subtypes are characterized by distinct biological behavior and vulnerabilities that can be therapeutically exploited. The PI3K/Akt/mTOR pathway is frequently affected in SCLC, and its activation represents a promising therapeutic target. Since the mTOR pathway is a master regulator of cellular metabolism, its alterations may also influence the bioenergetic processes of SCLC cells. Despite the encouraging preclinical results, both mTOR and metabolic inhibitors have met limited clinical success so far. Patient selection for personalized therapy, the development of rational drug combinations, and a better understanding of heterogeneity and spatiotemporal evolution of the tumor cells may improve efficacy and can help to overcome acquired resistance. Here we provide a summary of current investigations regarding the role of the mTOR pathway and metabolic alterations in the progression and metastasis formation of SCLC. Springer US 2021-12-27 2021 /pmc/articles/PMC8825381/ /pubmed/34958428 http://dx.doi.org/10.1007/s10555-021-10012-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Krencz, Ildiko
Sztankovics, Daniel
Danko, Titanilla
Sebestyen, Anna
Khoor, Andras
Progression and metastasis of small cell lung carcinoma: the role of the PI3K/Akt/mTOR pathway and metabolic alterations
title Progression and metastasis of small cell lung carcinoma: the role of the PI3K/Akt/mTOR pathway and metabolic alterations
title_full Progression and metastasis of small cell lung carcinoma: the role of the PI3K/Akt/mTOR pathway and metabolic alterations
title_fullStr Progression and metastasis of small cell lung carcinoma: the role of the PI3K/Akt/mTOR pathway and metabolic alterations
title_full_unstemmed Progression and metastasis of small cell lung carcinoma: the role of the PI3K/Akt/mTOR pathway and metabolic alterations
title_short Progression and metastasis of small cell lung carcinoma: the role of the PI3K/Akt/mTOR pathway and metabolic alterations
title_sort progression and metastasis of small cell lung carcinoma: the role of the pi3k/akt/mtor pathway and metabolic alterations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825381/
https://www.ncbi.nlm.nih.gov/pubmed/34958428
http://dx.doi.org/10.1007/s10555-021-10012-4
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