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Breaking the Crosstalk of the Cellular Tumorigenic Network in NSCLC by a Highly Effective Drug Combination

Dennis Gürgen, Theresia Conrad, Michael Becker, Susanne Sebens, Christoph Röcken, Jens Hoffmann, View ORCID ProfileStefan Langhammer
doi: https://doi.org/10.1101/2021.10.23.465545
Dennis Gürgen
1EPO Experimental Pharmacology & Oncology, Berlin, Germany
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Theresia Conrad
1EPO Experimental Pharmacology & Oncology, Berlin, Germany
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Michael Becker
1EPO Experimental Pharmacology & Oncology, Berlin, Germany
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Susanne Sebens
2Institute for Tumorbiology, University of Kiel, Kiel, Germany
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Christoph Röcken
3Institute for Pathology, University of Kiel, Kiel, Germany
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Jens Hoffmann
1EPO Experimental Pharmacology & Oncology, Berlin, Germany
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Stefan Langhammer
4life science consulting, Burgwedel, Germany
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  • ORCID record for Stefan Langhammer
  • For correspondence: langhammer@ls-consultant.net
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Abstract

Non-small cell lung cancer (NSCLC) is commonly diagnosed at advanced stages limiting treatment options. Although, targeted therapy has become integral part of NSCLC treatment therapies often fail to improve patient’s prognosis. Based on previously published criteria for selecting drug combinations for overcoming resistances, NSCLC patient-derived xenograft (PDX) tumors were treated with a low dose combination of cabozantinib, afatinib, plerixafor and etoricoxib.

All PDX tumors treated, including highly therapy-resistant adeno-and squamous cell carcinomas without identifiable driver mutations, were completely suppressed by this drug regimen, leading to an ORR of 81% and a CBR of 100%. The application and safety profile of this low dose therapy regimen was well manageable in the pre-clinical settings.

Overall, this study provides evidence of a relationship between active paracrine signaling pathways of the cellular tumorigenic network, which can be effectively targeted by a low-dose multimodal therapy to overcome therapy resistance and improve prognosis of NSCLC.

Competing Interest Statement

The authors Theresia Conrad, Michael Becker, Susanne Sebens and Christoph Roecken declare no conflict of interest. Jens Hoffmann, Dennis Guergen and Stefan Langhammer have issued a related patent, PCT/EP2021/072486. Jens Hoffmann declares the employment and the ownership of the EPO GmbH.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted October 23, 2021.
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Breaking the Crosstalk of the Cellular Tumorigenic Network in NSCLC by a Highly Effective Drug Combination
Dennis Gürgen, Theresia Conrad, Michael Becker, Susanne Sebens, Christoph Röcken, Jens Hoffmann, Stefan Langhammer
bioRxiv 2021.10.23.465545; doi: https://doi.org/10.1101/2021.10.23.465545
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Breaking the Crosstalk of the Cellular Tumorigenic Network in NSCLC by a Highly Effective Drug Combination
Dennis Gürgen, Theresia Conrad, Michael Becker, Susanne Sebens, Christoph Röcken, Jens Hoffmann, Stefan Langhammer
bioRxiv 2021.10.23.465545; doi: https://doi.org/10.1101/2021.10.23.465545

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