Three papers published this month in the open access general medical journal PLoS Medicine investigate how tumors respond to a an important class of drugs used in cancer chemotherapy, known as epidermal growth factor receptor (EGFR) inhibitors.
EGFR plays a critical role in the control of cellular proliferation, differentiation, and survival. Abnormalities in signaling of the EGFR pathway have been found in a wide range of cancers, including carcinomas of the lung, breast, and colon. Inhibitors of EGFR such as gefitinib are used in the treatment of these cancers, particularly non-small cell lung cancers which have mutations within the EGFR gene. However, the exact molecular mechanisms leading to tumor response to these drugs has been unclear.
The three independent studies with lead authors William Pao from Memorial Sloan Kettering, New York, Andreas Strasser from the Walter and Eliza Hall Institute Australia, and Susumu Kobayashi from Beth Israel Deaconess Medical Center, Boston, each investigated this pathway and show that that one protein, BIM, a member of a class of proteins that leads to apoptosis (programmed cell death) is essential for tumor cell killing by drugs such as gefitinib in cells with EGFR mutations. These results suggest that induction of BIM may in future lead to a way of treating tumors that have developed resistance to these drugs.
The papers are further discussed in a perspective by Ingo Mellinghoff from UCLA.
* * * * * * * * * EMBARGO: MONDAY, 29 October, 5 P.M. PDT * * * * * * * * * * *
Everything published by PLoS Medicine is Open Access: freely available for anyone to read, download, redistribute and otherwise use, as long as the authorship is properly attributed.
Citation: Gong Y, Somwar R, Politi K, Balak M, Chmielecki J, et al. (2007) Induction of BIM Is Essential for Apoptosis Triggered by EGFR Kinase Inhibitors in Mutant EGFR-Dependent Lung Adenocarcinomas. PLoS Med 4(10): e294
THIS PAPER WAS PUBLISHED ON THE 9TH OCTOBER AND IS FREELY AVAILABLE TO READ, DOWNLOAD AND DISTRIBUTE: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040294
CONTACT:
William Pao
Memorial Sloan-Kettering Cancer Center
Medicine/Human Oncology & Pathogenesis Progra
475 York Ave, Box 125
New York, NY 10021
United States of America
+1 646-888-2642
+1 646-888-2595 (fax)
paow@mskcc.org
Citation: Cragg MS, Kuroda J, Puthalakath H, Huang DCS, Strasser A (2007) Gefitinib-induced killing of NSCLC cell lines expressing mutant EGFR requires BIM and can be enhanced by BH3 mimetics. PLoS Med 4(10): e316.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040316
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-04-10-strasser.pdf
CONTACT:
Andreas Strasser
The Walter and Eliza Hall Institute
Molecular Genetics of Cancer
The Walter and Eliza Hall Institute 1G Royal Parade
Parkville, Victoria 3050
Australia
+44 02380 777222 x8056
+44 02380 704061 (fax)
strasser@wehi.edu.au
Citation: Costa DB, Halmos B, Kumar A, Schumer ST, Huberman MS, et al. (2007) BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosisin lung cancers with oncogenic EGFRmutations. PLoS Med 4(10): e315.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040315
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-04-10-kobayashi.pdf
CONTACT:
Susumu Kobayashi
Beth Israel Deaconess Medical Center
Division of Hematology/Oncology
Harvard Institutes of Medicine
Boston, MA 02115
United States of America
+1 617-667-4272, 5561
+1 617-667-3299 (fax)
skobayas@bidmc.harvard.edu
Related PLoS Medicine Perspective:
Citation: Mellinghoff I (2007) Why do cancer cells become “addicted” to oncogenic epidermal growth factor receptor" PLoS Med 4( 0): e321
IN YOUR ARTICLE, PLEASE LINK TO THIS URL, WHICH WILL PROVIDE ACCESS TO THE PUBLISHED PAPER: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040321
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-04-10-mellinghoff.pdf
CONTACT:
Ingo Mellinghoff
University of California, Los Angeles
Pharmacology
700 Westwood Plaza, B3-399 BRI
Los Angeles, CA 90095
United States of America
+1 310-825-2294
imellinghoff@mednet.ucla.edu
About PLoS Medicine
PLoS Medicine is an open access, freely available international medical journal. It publishes original research that enhances our understanding of human health and disease, together with commentary and analysis of important global health issues. For more information, visit http://www.plosmedicine.org
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org
Journal
PLoS Medicine