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Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer

A critical decline of functional insulin-producing pancreatic β-cells is the central pathologic element of both type 1 and type 2 diabetes. Mammalian Sterile 20-like kinase 1 (MST1) is a key mediator of β-cell failure and the identification of neratinib as MST1 inhibitor with potent effects on β-cel...

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Autores principales: Angelis, Vasileios, Johnston, Stephen R. D., Ardestani, Amin, Maedler, Kathrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968155/
https://www.ncbi.nlm.nih.gov/pubmed/35370966
http://dx.doi.org/10.3389/fendo.2022.830097
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author Angelis, Vasileios
Johnston, Stephen R. D.
Ardestani, Amin
Maedler, Kathrin
author_facet Angelis, Vasileios
Johnston, Stephen R. D.
Ardestani, Amin
Maedler, Kathrin
author_sort Angelis, Vasileios
collection PubMed
description A critical decline of functional insulin-producing pancreatic β-cells is the central pathologic element of both type 1 and type 2 diabetes. Mammalian Sterile 20-like kinase 1 (MST1) is a key mediator of β-cell failure and the identification of neratinib as MST1 inhibitor with potent effects on β-cell survival represents a promising approach for causative diabetes therapy. Here we report a case of robust glycemia and HbA1c normalization in a patient with breast cancer-T2D comorbidity under neratinib, a potent triple kinase inhibitor of HER2/EGFR and MST1. The patient, aged 62 years, was enrolled in the plasmaMATCH clinical trial and received 240 mg neratinib once daily. Neratinib therapy correlated with great improvement in glucose and HbA1c both to physiological levels during the whole treatment period (average reduction of random glucose from 13.6 ± 0.4 to 6.3 ± 0.5 mmol/l and of HbA1c from 82.2 ± 3.9 to 45.6 ± 4.2 mmol/mol before and during neratinib). 18 months later, when neratinib was withdrawn, random glucose rapidly raised together with high blood glucose fluctuations, which reflected in elevated HbA1c levels. This clinical case reports the combination of HER2/EGFR/MST1-inhibition by neratinib for the pharmacological intervention to effectively restore normoglycemia in a patient with poorly controlled T2D and suggests neratinib as potent therapeutic regimen for the cancer-diabetes comorbidity.
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spelling pubmed-89681552022-04-01 Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer Angelis, Vasileios Johnston, Stephen R. D. Ardestani, Amin Maedler, Kathrin Front Endocrinol (Lausanne) Endocrinology A critical decline of functional insulin-producing pancreatic β-cells is the central pathologic element of both type 1 and type 2 diabetes. Mammalian Sterile 20-like kinase 1 (MST1) is a key mediator of β-cell failure and the identification of neratinib as MST1 inhibitor with potent effects on β-cell survival represents a promising approach for causative diabetes therapy. Here we report a case of robust glycemia and HbA1c normalization in a patient with breast cancer-T2D comorbidity under neratinib, a potent triple kinase inhibitor of HER2/EGFR and MST1. The patient, aged 62 years, was enrolled in the plasmaMATCH clinical trial and received 240 mg neratinib once daily. Neratinib therapy correlated with great improvement in glucose and HbA1c both to physiological levels during the whole treatment period (average reduction of random glucose from 13.6 ± 0.4 to 6.3 ± 0.5 mmol/l and of HbA1c from 82.2 ± 3.9 to 45.6 ± 4.2 mmol/mol before and during neratinib). 18 months later, when neratinib was withdrawn, random glucose rapidly raised together with high blood glucose fluctuations, which reflected in elevated HbA1c levels. This clinical case reports the combination of HER2/EGFR/MST1-inhibition by neratinib for the pharmacological intervention to effectively restore normoglycemia in a patient with poorly controlled T2D and suggests neratinib as potent therapeutic regimen for the cancer-diabetes comorbidity. Frontiers Media S.A. 2022-03-17 /pmc/articles/PMC8968155/ /pubmed/35370966 http://dx.doi.org/10.3389/fendo.2022.830097 Text en Copyright © 2022 Angelis, Johnston, Ardestani and Maedler 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 Endocrinology
Angelis, Vasileios
Johnston, Stephen R. D.
Ardestani, Amin
Maedler, Kathrin
Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer
title Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer
title_full Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer
title_fullStr Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer
title_full_unstemmed Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer
title_short Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer
title_sort case report: neratinib therapy improves glycemic control in a patient with type 2 diabetes and breast cancer
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968155/
https://www.ncbi.nlm.nih.gov/pubmed/35370966
http://dx.doi.org/10.3389/fendo.2022.830097
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