Lung Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Lung Cancer, including details on symptoms, smoking, genetics, treatment, causes. | ||||||
|
FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR.Bivona TG, Hieronymus H, Parker J, Chang K, Taron M, Rosell R, Moonsamy P, Dahlman K, Miller VA, Costa C, Hannon G, Sawyers CL Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA. Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient. This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-κB pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-κB through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of IκB (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-κB enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-κB inhibitor IκB predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-κB as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence. Published 24 March 2011 in Nature, 471(7339): 523-6. Articles on Lung Cancer published 22 March 2011: Chemoresistance of lung cancer stemlike cells depends on activation of Hsp27. Cancer, 117(7): 1516-28. Racial disparities in the use of hospice services according to geographic residence and socioeconomic status in an elderly cohort with nonsmall cell lung cancer. Cancer, 117(7): 1506-15. Articles on Lung Cancer published 15 March 2011: Claudin-2 knockdown decreases matrix metalloproteinase-9 activity and cell migration via suppression of nuclear Sp1 in A549 cells. Life Sci, 88(13): 628-33. Articles on Lung Cancer published 10 March 2011: Treatment of non-small-cell lung cancer with erlotinib or gefitinib. N Engl J Med, 364(10): 947-55. A 64-year-old woman receives the diagnosis of metastatic non-small-cell lung cancer (NSCLC), which has progressed during treatment with carboplatin, paclitaxel, and bevacizumab. Erlotinib therapy is recommended. [Abstract] [Full-text] Treatment of non-small-cell lung cancer with erlotinib or gefitinib. N Engl J Med, 364(10): 947-55. A 64-year-old woman receives the diagnosis of metastatic non-small-cell lung cancer (NSCLC), which has progressed during treatment with carboplatin, paclitaxel, and bevacizumab. Erlotinib therapy is recommended. [Abstract] [Full-text] Articles on Lung Cancer published 1 March 2011: Topotecan for relapsed small cell lung cancer: a systematic review and economic evaluation. Cancer Treat Rev, 37(3): 242-9. Articles on Lung Cancer published 28 February 2011: Radiotherapy in small-cell lung cancer: lessons learned and future directions. Int J Radiat Oncol Biol Phys, 79(4): 998-1003. Although chemotherapy is an essential component in the treatment of small-cell lung cancer, improvements in survival in the past two decades have been mainly achieved by the appropriate application of radiotherapy. The aim of the present study was to review the key developments in thoracic radiotherapy and prophylactic cranial radiotherapy and to discuss the rationale behind key ongoing studies in small-cell lung cancer. [Abstract] [Full-text] Combination of anti-IGF-1R antibody A12 and ionizing radiation in upper respiratory tract cancers. Int J Radiat Oncol Biol Phys, 79(4): 1179-87. © 2004-2011 Lung Cancer Research Today. All Rights Reserved. |
| ||||
