The ABC7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy

Richard E Kast,1 Nicolas Skuli,2 Samuel Cos,3 Georg Karpel-Massler,4 Yusuke Shiozawa,5 Ran Goshen,6 Marc-Eric Halatsch4 1IIAIGC Study Center, Burlington, VT, USA; 2INSERM, Centre de Recherches en Cancérologie de Toulouse – CRCT, UMR1037 Inserm/Université Toulouse III...

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Autores principales: Kast RE, Skuli N, Cos S, Karpel-Massler G, Shiozawa Y, Goshen R, Halatsch ME
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:4e6e679f64db42edab80fb791718a6242021-12-02T04:17:35ZThe ABC7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy1179-1314https://doaj.org/article/4e6e679f64db42edab80fb791718a6242017-07-01T00:00:00Zhttps://www.dovepress.com/the-abc7-regimen-a-new-approach-to-metastatic-breast-cancer-using-seve-peer-reviewed-article-BCTThttps://doaj.org/toc/1179-1314Richard E Kast,1 Nicolas Skuli,2 Samuel Cos,3 Georg Karpel-Massler,4 Yusuke Shiozawa,5 Ran Goshen,6 Marc-Eric Halatsch4 1IIAIGC Study Center, Burlington, VT, USA; 2INSERM, Centre de Recherches en Cancérologie de Toulouse – CRCT, UMR1037 Inserm/Université Toulouse III – Paul Sabatier, Toulouse, France; 3Department of Physiology and Pharmacology, School of Medicine, University of Cantabria and Valdecilla Research Institute (IDIVAL), Santander, Spain; 4Department of Neurosurgery, Ulm University Hospital, Ulm, Germany; 5Department of Cancer Biology, Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, USA; 6Eliaso Consulting Ltd., Tel Aviv-Yafo, Israel Abstract: Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities. Chemotherapy, radiation, and surgery provoke EMT in cancer generally and in breast cancer specifically. ABC7 uses standard doses of capecitabine as used in treating breast cancer today. In addition, ABC7 uses 1) an older psychiatric drug, quetiapine, to block RANK signaling; 2) pirfenidone, an anti-fibrosis drug to block TGF-beta signaling; 3) rifabutin, an antibiotic to block beta-catenin signaling; 4) metformin, a first-line antidiabetic drug to stimulate AMPK and inhibit mammalian target of rapamycin, (mTOR); 5) propranolol, a beta-blocker to block beta-adrenergic signaling; 6) agomelatine, a melatonergic antidepressant to stimulate M1 and M2 melatonergic receptors; and 7) ribavirin, an antiviral drug to prevent eIF4E phosphorylation. All these block the signaling pathways – RANK, TGF-beta, mTOR, beta-adrenergic receptors, and phosphorylated eIF4E – that have been shown to trigger EMT and enhance breast cancer growth and so are worthwhile targets to inhibit. Agonism at MT1 and MT2 melatonergic receptors has been shown to inhibit both breast cancer EMT and growth. This ensemble was designed to be safe and augment capecitabine efficacy. Given the expected outcome of metastatic breast cancer as it stands today, ABC7 warrants a cautious trial. Keywords: ABC7, breast cancer, agomelatine, capecitabine, metformin, pirfenidone, propranolol, quetiapine, repurposing, ribavirin, rifabutin, TGF-betaKast RESkuli NCos SKarpel-Massler GShiozawa YGoshen RHalatsch MEDove Medical PressarticleABC7breast canceragomelatinecapecitabinemetforminpirfenidonepropranololquetiapinerepurposingribavirinrifabutinTGF-betaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol Volume 9, Pp 495-514 (2017)
institution DOAJ
collection DOAJ
language EN
topic ABC7
breast cancer
agomelatine
capecitabine
metformin
pirfenidone
propranolol
quetiapine
repurposing
ribavirin
rifabutin
TGF-beta
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle ABC7
breast cancer
agomelatine
capecitabine
metformin
pirfenidone
propranolol
quetiapine
repurposing
ribavirin
rifabutin
TGF-beta
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Kast RE
Skuli N
Cos S
Karpel-Massler G
Shiozawa Y
Goshen R
Halatsch ME
The ABC7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy
description Richard E Kast,1 Nicolas Skuli,2 Samuel Cos,3 Georg Karpel-Massler,4 Yusuke Shiozawa,5 Ran Goshen,6 Marc-Eric Halatsch4 1IIAIGC Study Center, Burlington, VT, USA; 2INSERM, Centre de Recherches en Cancérologie de Toulouse – CRCT, UMR1037 Inserm/Université Toulouse III – Paul Sabatier, Toulouse, France; 3Department of Physiology and Pharmacology, School of Medicine, University of Cantabria and Valdecilla Research Institute (IDIVAL), Santander, Spain; 4Department of Neurosurgery, Ulm University Hospital, Ulm, Germany; 5Department of Cancer Biology, Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, USA; 6Eliaso Consulting Ltd., Tel Aviv-Yafo, Israel Abstract: Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities. Chemotherapy, radiation, and surgery provoke EMT in cancer generally and in breast cancer specifically. ABC7 uses standard doses of capecitabine as used in treating breast cancer today. In addition, ABC7 uses 1) an older psychiatric drug, quetiapine, to block RANK signaling; 2) pirfenidone, an anti-fibrosis drug to block TGF-beta signaling; 3) rifabutin, an antibiotic to block beta-catenin signaling; 4) metformin, a first-line antidiabetic drug to stimulate AMPK and inhibit mammalian target of rapamycin, (mTOR); 5) propranolol, a beta-blocker to block beta-adrenergic signaling; 6) agomelatine, a melatonergic antidepressant to stimulate M1 and M2 melatonergic receptors; and 7) ribavirin, an antiviral drug to prevent eIF4E phosphorylation. All these block the signaling pathways – RANK, TGF-beta, mTOR, beta-adrenergic receptors, and phosphorylated eIF4E – that have been shown to trigger EMT and enhance breast cancer growth and so are worthwhile targets to inhibit. Agonism at MT1 and MT2 melatonergic receptors has been shown to inhibit both breast cancer EMT and growth. This ensemble was designed to be safe and augment capecitabine efficacy. Given the expected outcome of metastatic breast cancer as it stands today, ABC7 warrants a cautious trial. Keywords: ABC7, breast cancer, agomelatine, capecitabine, metformin, pirfenidone, propranolol, quetiapine, repurposing, ribavirin, rifabutin, TGF-beta
format article
author Kast RE
Skuli N
Cos S
Karpel-Massler G
Shiozawa Y
Goshen R
Halatsch ME
author_facet Kast RE
Skuli N
Cos S
Karpel-Massler G
Shiozawa Y
Goshen R
Halatsch ME
author_sort Kast RE
title The ABC7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy
title_short The ABC7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy
title_full The ABC7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy
title_fullStr The ABC7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy
title_full_unstemmed The ABC7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy
title_sort abc7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/4e6e679f64db42edab80fb791718a624
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