ScienceDaily (Nov. 2, 2007) — 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.

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

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.

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.

Citation: Mellinghoff I (2007) Why do cancer cells become "addicted" to oncogenic epidermal growth factor receptor? PLoS Med 4( 0): e321

Related Stories

Resistance To Chemotherapy: How Tumors Acquire Resistance To Kinase Inhibitors (Mar. 7, 2005) — Acquired resistance to chemotherapy is a major obstacle to successful cancer treatment. Understanding the mechanisms by which tumors become resistant to a particular agent is key to identifying new ...  > read more

Significant Benefits In Non-small-cell Lung Cancer From Customizing Erlotinib Treatment (Sep. 15, 2008) — Lung cancer patients whose tumors carry specific genetic mutations can achieve significantly longer survival when treated with targeted therapies such as erlotinib, researchers ...  > read more

Targeting Lung Cancer (May 17, 2006) — As reported in the June 1 issue of G&D, Drs. Katerina Politi, Harold Varmus and colleagues at the Memorial Sloan Kettering Cancer Center in New York have developed a novel animal model of lung ...  > read more

Role For Gefitinib In Asian Nonsmokers With Lung Cancer Established (Sep. 16, 2008) — The targeted therapy gefitinib should be considered a first-line therapy for nonsmoking Asian patients with adenocarcinoma of the lung, one of the most common types of lung cancer, suggests a ...  > read more

Search ScienceDaily

Beating Bone Marrow Cancer