Sensitization of EGFR Wild-Type Non-Small Cell Lung Cancer Cells to EGFR-Tyrosine Kinase Inhibitor Erlotinib

Molecular Cancer Therapeutics
Judith RaimbourgLisenn Lalier

Abstract

The benefit of EGFR-TKI in non-small cell lung cancer has been demonstrated in mutant EGFR tumors as first-line treatment but the benefit in wild-type EGFR tumors is marginal as well as restricted to maintenance therapy in pretreated patients. This work aimed at questioning the effects of cisplatin initial treatment on the EGFR pathway in non-small cell lung cancer and the functional consequences in vitro and in in vivo animal models of patient-derived xenografts (PDX). We establish here that cisplatin pretreatment specifically sensitizes wild-type EGFR-expressing cells to erlotinib, contrary to what happens in mutant EGFR cells and with a blocking EGFR antibody, both in vitro and in vivo The sensitization entails the activation of the kinase Src upstream of EGFR, thereafter transactivating EGFR through a ligand-independent activation. We propose a combination of markers that enable to discriminate between the tumors sensitized to erlotinib or not in PDX models, which should be worth testing in patients. These markers might be useful for the selection of patients who would benefit from erlotinib as a maintenance therapy. Mol Cancer Ther; 16(8); 1634-44. ©2017 AACR.

References

May 20, 2004·American Journal of Physiology. Renal Physiology·Istvan AranyRobert L Safirstein
Feb 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey A EngelmanLewis C Cantley
Mar 5, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Qun DaiRoman Perez-Soler
Apr 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ulrich GatzemeierJoachim Von Pawel
Mar 14, 2008·The New England Journal of Medicine·Fortunato Ciardiello, Giampaolo Tortora
Jun 18, 2009·Traffic·Kirstine RoepstorffBo van Deurs
Sep 10, 2009·Science Signaling·Paul H HuangForest M White
Jun 17, 2010·Nature Reviews. Clinical Oncology·Filip JankuRazelle Kurzrock
Nov 17, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christina L AddisonPenelope A Bradbury
May 26, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·B CoudertUNKNOWN SATURN Investigators
Oct 5, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Wolfram BruggerFederico Cappuzzo
Jan 17, 2012·Journal of the National Cancer Institute·Nathan T IhleGarth Powis
Aug 25, 2012·Cell Cycle·Lorenzo GalluzziGuido Kroemer
Jan 7, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ning LuFang Yan
May 17, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Katerina Politi, Roy S Herbst
Jul 1, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Erin L StewartMing-Sound Tsao
Aug 19, 2015·Cancer Research·Gao GuoAmyn A Habib
Aug 3, 2016·The Journal of Clinical Investigation·Dana M HardbowerKeith T Wilson

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.