Inflammation in lung carcinogenesis: new targets for lung cancer chemoprevention and treatment.
Lung carcinogenesis is a complex process involving the acquisition of genetic mutations that confer cancer development and the malignant phenotype, and is critically linked to apoptosis resistance, unregulated proliferation, invasion, metastasis, and angiogenesis. Epithelial mesenchymal transition (EMT) in cancer is an unregulated process in a host environment with deregulated inflammatory response that impairs cell-mediated immunity and permits cancer progression. Given the immunosuppressive tumor environment, strategies to reverse these events by stimulating host immune responses are an important area of investigation. Cyclooxygenase 2 (COX-2) and its downstream signaling pathways are potential targets for lung cancer chemoprevention and therapy. Clinical trials are underway to evaluate COX-2 inhibitors as adjuvants to chemotherapy in patients with lung cancer and to determine efficacy in prevention of bronchogenic carcinoma. The understanding of molecular mechanisms involved in inflammation and lung carcinogenesis provide insight for new drug development that target reversible, non-mutational events in the chemoprevention and treatment of lung cancer.
Lee
Jay M
JM
Division of Cardiothoracic Surgery, Department of Surgery, UCLA Lung Cancer Research Program, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. jaymoonlee@mednet.ucla.edu
Yanagawa
Jane
J
Peebles
Katherine A
KA
Sharma
Sherven
S
Mao
Jenny T
JT
Dubinett
Steven M
SM
D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D018773:Genes, erbB-1; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D051546:Cyclooxygenase 2; D066246:ErbB Receptors