Understanding the mechanisms of drug-associated interstitial lung disease.
Drugs have been implicated in lung injury as a result of direct pharmacological action, persistence or metabolism in the tissue, or via the production of a reactive metabolite or metabolites. The result of this apparent drug-associated injury ranges from cellular dysfunction through to cell death (apoptosis) and alteration of repair mechanisms that are essential in replacing critical tissue elements and function. There is limited knowledge on how timing of drug administration or drug interactions may interfere with the repair mechanisms or modulate the expression of pulmonary toxicity. Chemotherapeutic drugs and novel agents, such as those targeting the epidermal growth factor receptor (EGFR), appear to affect both normal and neoplastic cells. However, unlike chemotherapy, where the actions are systemic and directly as a result of biotransformation or cell injury, it has been postulated that effects of EGFR-targeting agents are more likely to be focused on epithelia via a pharmacological effect. Furthermore, risk factors for the development of adverse pulmonary reactions, as well as biological markers indicating incipient toxicity, need to be prospectively identified. Proteomics, through the identification of >/=1000 proteins or peptides in blood samples, will hopefully identify candidates for this role.
Higenbottam
T
T
Global Clinical Science, AstraZeneca R&D, Charnwood, Bakewell Road, Loughborough, Leicester LE11 5RH, UK. tim.hidenbottam@astrazeneca.com
Kuwano
K
K
Nemery
B
B
Fujita
Y
Y
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D001711:Biotransformation; D003131:Combined Modality Therapy; D004847:Epithelial Cells; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000503:physiopathology*; D008175:Lung Neoplasms / Q000188:drug therapy*; D040901:Proteomics; D011832:Radiation Injuries; D012307:Risk Factors
D015415:Biomarkers; D066246:ErbB Receptors