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43 - Lung cancer
- from Part 3.1 - Molecular pathology: carcinomas
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- By Jill E. Larsen, Hamon Center for herapeutic Oncology Research, Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA, John D. Minna, Hamon Center for herapeutic Oncology Research, Simmons Cancer Center University of Texas Southwestern Medical Center, Dallas, TX, USA
- Edited by Edward P. Gelmann, Columbia University, New York, Charles L. Sawyers, Memorial Sloan-Kettering Cancer Center, New York, Frank J. Rauscher, III
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- Book:
- Molecular Oncology
- Published online:
- 05 February 2015
- Print publication:
- 19 December 2013, pp 506-525
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Summary
DNA damage leads to lung cancer
Approximately 85% of lung cancers are caused by tobacco-smoke-acquired carcinogenesis, while worldwide, ~15–25% of lung cancer cases occur in lifetime “never smokers” (less than 100 cigarettes in a lifetime). These etiologic differences are associated with distinct differences in tumor-acquired molecular changes, such as EGFR mutations in never-smoking lung cancers (1,2). Of importance, with cessation of cigarette smoking from public health initiatives, ~50% of all newly diagnosed cases of lung cancer occur in former smokers who ceased smoking >5 years previously. Never-smoking lung cancers represent a distinct disease that occurs more frequently in women and East Asians, targets the distal airways, is usually adenocarcinoma, and frequently has acquired EGFR mutations making it very responsive to EGFR-targeted therapies (1). A multi-step process involving genetic and epigenetic alterations resulting from DNA damage (usually from cigarette smoking) transforms normal lung epithelium into lung cancer and results in “field defects” in histologically normal lung epithelium, as well as a variety of histologic pre-neoplastic/pre-malignant lesions (3,4). The culmination of these changes lead to lung cancers exhibiting all six of the “hallmarks of cancer” (self-sufficiency of growth signals, insensitivity to growth-inhibitory (anti-growth) signals, evasion of programmed cell death (apoptosis), limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis; 5). Current information on the molecular steps and their timing in pre-neoplasia, primary cancer, and metastatic disease is the subject of this chapter (6). The identification and characterization of key molecular changes – often involving oncogenes and tumor suppressor genes (TSGs), and importantly, the associated “tumor cell vulnerabilities” that accompany these oncogenotype changes – in the development and progression of lung cancer are of fundamental importance for improving the prevention, early detection, and treatment of this disease. Ultimately these findings need to be translated to the clinic by using molecular alterations, such as biomarkers for early detection, targets for prevention, signatures for personalizing prognosis and therapy selection for each patient, and therapeutic targets to selectively kill or inhibit the growth of lung cancer.
Excavations at Tell Brak 1998: Preliminary report
- Geoff Emberling, Jack Cheng, Torben E. Larsen, Holly Pittman, Tim B. B. Skuldboel, Jill Weber, Henry T. Wright
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The 22nd season of excavations at Tell Brak took place in April and May of 1998, with David Oates as Project Director and Geoff Emberling as Field Director. It is our pleasure to mention institutions and people who made the project such a success. This season was primarily funded by the Adelaide Milton de Groot Fund (in memory of the de Groot and Hawley families) of The Metropolitan Museum of Art. The Carsten Niebuhr Institute of the University of Copenhagen, Dell Computer Corporation and the Museum of Anthropology of the University of Michigan also generously provided funds and equipment. We would like to thank Dr Sultan Muhesen, Director-General of Antiquities and Museums in Syria, for his encouragement and interest, as well as Dr Adnan Bounni, Director of Excavations, and our representative, Abd el Messih Baghdo. The excavation team this season was exceptionally enthusiastic and dedicated. Jack Cheng was registrar, a position that included designing an excavation database as well as photography and drawing; Tim Skuldboel and Torben Larsen were surveyors; Lisa Cooper, Zenia Hoeserich, Stine Rossel, Suanna Selby and Laura Tedesco were site supervisors; Michael Charles and Mette Marie Hald supervised the notation program; Jill Weber worked on faunal material; Jean-François de Lapérouse of the Metropolitan Museum was objects conservator; Henry Wright analysed samples of chipped stone; and Donald Hansen and Joan Oates gave crucial help in architecture, excavation and ceramic analysis. David Oates provided helpful advice and support. We thank them all for their many contributions to work in the field and to this report.