Synergistic anticancer activity of arsenic trioxide with erlotinib is based on inhibition of EGFR-mediated DNA double strand break repair

We show that inhibition of arsenic trioxide (ATO)-mediated epidermal growth factor receptor (EGFR) activation can be used to potently sensitize diverse solid cancer types against ATO. A combination of ATO and EGFR inhibitors is a promising therapeutic strategy against various solid tumors harboring wild-type EGFR.

KRAS Mutation as the Biomarker of Response to Chemotherapy and EGFR-TKIs in Patients With Advanced Non-Small Cell Lung Cancer: Clues For Its Potential Use in Second-Line Therapy Decision Making

In patients with non-small cell lung cancer (NSCLC), knowledge of the epidermal growth factor receptor (EGFR) mutation status is fundamental for selecting the treatment involving EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Little information is available regarding the response and progression-free survival (PFS) in platinum-based chemotherapy (CT) versus EGFR-TKIs in the presence or absence of KRAS mutation, particularly in patients without EGFR mutation…”

PUMA and BIM Are Required for Oncogene Inactivation-Induced Apoptosis

The clinical efficacy of tyrosine kinase inhibitors supports the dependence of distinct subsets of cancers on specific driver mutations for survival, a phenomenon called “oncogene addiction.” We demonstrate that PUMA and BIM are the key apoptotic effectors of tyrosine kinase inhibitors in breast cancers with amplification of the gene encoding human epidermal growth factor receptor 2 (HER2) and lung cancers with epidermal growth factor receptor (EGFR) mutants…”

Switching from Iressa to Tarceva Halts Drug-Induced Immune Suppression in Lung Cancer Patient

Neutropenia (a reduction in white blood cells) is a rare, but potentially serious side effect of the cancer drug gefitinib (Iressa). Iressa is used to treat non-small cell lung cancer (NSCLC) with mutations in the EGFR gene. A patient with EGFR-mutant advanced adenocarcinoma of the lung (a type of NSCLC) was treated with Iressa. Her tumor shrank, but she experienced severe neutropenia, leaving her at risk of dangerous infections. She was switched to erlotinib (Tarceva), another EGFR inhibitor, after which her neutropenia cleared up. The patient has since continued on Tarceva without neutropenia or cancer progression for over 9 months. This case suggests that Iressa-induced neutropenia can be safely treated by switching to Tarceva, although caution should be used in drawing conclusions from a single case study.

From GRACE: Molecular Markers: The More You Seek, the More You Find

This week, we borrow a post from the excellent website of the Global Resource for Advancing Cancer Education (GRACE). GRACE founder and president Dr. Jack West is an oncologist who treats people with lung cancer. In the video below, he discusses his evolving views on molecular testing. To see the original post, and to explore the many other resources offered by GRACE, click here.

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Dachshund Binds p53 To Block The Growth of Lung Adenocarcinoma Cells

Given the importance of EGFR signaling in lung cancer etiology, we examined the role of Drosophila gene Dachshund DACH1 expression in lung cancer development. We conclude that DACH1 binds p53 to inhibit NSCLC cellular growth.

Tarceva Improves Quality of Life in Certain Lung Cancer Patients

Updated results from a clinical trial showed that patients who were treated with the drug erlotinib (Tarceva) had better quality of life than those receiving standard chemotherapy. The OPTIMAL study is a phase III clinical trial investigating erlotinib (Tarceva) as a first-line treatment for people with advanced non-small cell lung cancer (NSCLC) who have a mutation in the EGFR gene. Tarceva-treated patients scored higher on questionnaires assessing physical, social/family, emotional, and functional well-being. The updated results also confirmed that Tarceva-treated patients experienced longer periods without worsening of their cancer compared to chemotherapy-treated patients.

Quality of life analyses from OPTIMAL (CTONG-0802), a phase III study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutation-positive NSCLC

The OPTIMAL study found that erlotinib improved progression-free survival (PFS) versus standard chemotherapy in Chinese patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). This report describes the quality of life (QoL) and updated PFS analyses from this study.

Erlotinib improves QoL compared with standard chemotherapy in the first-line treatment of patients with EGFR mutation-positive advanced NSCLC.

CNS metastases in non-small-cell lung cancer: Current role of EGFR-TKI therapy and future perspectives

In NSCLC patients with activating epidermal growth factor receptor gene (EGFR) mutations EGFR-specific tyrosine kinase inhibitors (TKI) represent effective and well tolerated modes of therapy, however, it has been unclear whether these drugs are also able to cross the blood–brain-barrier (BBB) and cause remission of CNS metastases. Recent studies suggest that this might indeed be the case and intracerebral response rates of 70–80% in molecularly selected patients are considerably higher compared to what would be expected for standard approaches like systemic chemotherapy and whole brain radiation therapy.