RT Journal Article
SR Electronic
T1 Breaking the Crosstalk of the Cellular Tumorigenic Network in NSCLC by a Highly Effective Drug Combination
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.23.465545
DO 10.1101/2021.10.23.465545
A1 Dennis Gürgen
A1 Theresia Conrad
A1 Michael Becker
A1 Susanne Sebens
A1 Christoph Röcken
A1 Jens Hoffmann
A1 Stefan Langhammer
YR 2021
UL http://biorxiv.org/content/early/2021/10/23/2021.10.23.465545.abstract
AB 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 StatementThe 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.