Book contents
- Frontmatter
- Dedication
- Contents
- List of Contributors
- Preface
- Part 1.1 Analytical techniques: analysis of DNA
- Part 1.2 Analytical techniques: analysis of RNA
- Part 2.1 Molecular pathways underlying carcinogenesis: signal transduction
- Part 2.2 Molecular pathways underlying carcinogenesis: apoptosis
- Part 2.3 Molecular pathways underlying carcinogenesis: nuclear receptors
- Part 2.4 Molecular pathways underlying carcinogenesis: DNA repair
- Part 2.5 Molecular pathways underlying carcinogenesis: cell cycle
- Part 2.6 Molecular pathways underlying carcinogenesis: other pathways
- Part 3.1 Molecular pathology: carcinomas
- 42 Head and neck cancer
- 43 Lung cancer
- 44 Esophageal cancer
- 45 Gastric cancer
- 46 Small-bowel tumors: molecular mechanisms and targeted therapy
- 47 Colon and rectal cancer
- 48 Pancreatic cancer
- 49 Hepatocellular carcinoma
- 50 Renal-cell carcinomas
- 51 Bladder cancer
- 52 Prostate cancer
- 53 Targeted therapies in breast cancer
- 54 Molecular targets for epithelial ovarian cancer
- 55 Testicular cancer: germ-cell tumors (GCTs)
- 56 Cervical cancer
- Part 3.2 Molecular pathology: cancers of the nervous system
- Part 3.3 Molecular pathology: cancers of the skin
- Part 3.4 Molecular pathology: endocrine cancers
- Part 3.5 Molecular pathology: adult sarcomas
- Part 3.6 Molecular pathology: lymphoma and leukemia
- Part 3.7 Molecular pathology: pediatric solid tumors
- Part 4 Pharmacologic targeting of oncogenic pathways
- Index
- References
43 - Lung cancer
from Part 3.1 - Molecular pathology: carcinomas
Published online by Cambridge University Press: 05 February 2015
- Frontmatter
- Dedication
- Contents
- List of Contributors
- Preface
- Part 1.1 Analytical techniques: analysis of DNA
- Part 1.2 Analytical techniques: analysis of RNA
- Part 2.1 Molecular pathways underlying carcinogenesis: signal transduction
- Part 2.2 Molecular pathways underlying carcinogenesis: apoptosis
- Part 2.3 Molecular pathways underlying carcinogenesis: nuclear receptors
- Part 2.4 Molecular pathways underlying carcinogenesis: DNA repair
- Part 2.5 Molecular pathways underlying carcinogenesis: cell cycle
- Part 2.6 Molecular pathways underlying carcinogenesis: other pathways
- Part 3.1 Molecular pathology: carcinomas
- 42 Head and neck cancer
- 43 Lung cancer
- 44 Esophageal cancer
- 45 Gastric cancer
- 46 Small-bowel tumors: molecular mechanisms and targeted therapy
- 47 Colon and rectal cancer
- 48 Pancreatic cancer
- 49 Hepatocellular carcinoma
- 50 Renal-cell carcinomas
- 51 Bladder cancer
- 52 Prostate cancer
- 53 Targeted therapies in breast cancer
- 54 Molecular targets for epithelial ovarian cancer
- 55 Testicular cancer: germ-cell tumors (GCTs)
- 56 Cervical cancer
- Part 3.2 Molecular pathology: cancers of the nervous system
- Part 3.3 Molecular pathology: cancers of the skin
- Part 3.4 Molecular pathology: endocrine cancers
- Part 3.5 Molecular pathology: adult sarcomas
- Part 3.6 Molecular pathology: lymphoma and leukemia
- Part 3.7 Molecular pathology: pediatric solid tumors
- Part 4 Pharmacologic targeting of oncogenic pathways
- Index
- References
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.
- Type
- Chapter
- Information
- Molecular OncologyCauses of Cancer and Targets for Treatment, pp. 506 - 525Publisher: Cambridge University PressPrint publication year: 2013