Preclinical strategies targeted at non-small-cell lung cancer signalling pathways with striking translational fallout

► Improvement of NSCLC patients outcome with conventional cytotoxic agents is poor. ► Many processes involved in NSCLC development and genetic aetiology have been defined. ► EGFR and c-MetR mutants in NSCLC are intriguing targets for specific inhibitors. ► Drug resistance might be overcome targeting...

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Bibliographic Details
Published in:Drug discovery today 2013-01, Vol.18 (1-2), p.11-24
Main Authors: Favoni, Roberto E., Alama, Angela
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacology
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - pathology
Drug Design
Drug Evaluation, Preclinical
Humans
Lung Neoplasms - drug therapy
Lung Neoplasms - pathology
Molecular Targeted Therapy
Signal Transduction - drug effects
Survival Rate
Translational Medical Research - methods
Treatment Outcome
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Summary:► Improvement of NSCLC patients outcome with conventional cytotoxic agents is poor. ► Many processes involved in NSCLC development and genetic aetiology have been defined. ► EGFR and c-MetR mutants in NSCLC are intriguing targets for specific inhibitors. ► Drug resistance might be overcome targeting Cancer-Initiating Cells. ► Combination of targeted and standard therapies is promising in NSCLC management. Over the past decades, a plethora of cytotoxic agents, administered alone or in combinations, have been prescribed for the treatment of non-small-cell lung cancer (NSCLC) but improvements regarding patient outcome remain disappointing. Therefore, additional therapeutic strategies are urgently required to increase response rate and survival. By the time researchers had begun to understand the processes involved in NSCLC development, the genetic aetiology of lung cancer had been progressively defined. The constitutive activation of receptor tyrosine kinases and their downstream signalling pathways has opened encouraging avenues of investigation for NSCLC treatment. Several new targeted compounds have evolved from preclinical to clinical settings to affect growth factor pathways of NSCLC, and their therapeutic implications will be reviewed and discussed here. An updated overview of the most recent findings and therapeutic approaches in lung cancer from preclinical to clinical settings is reported and discussed.
ISSN:1359-6446
1878-5832
DOI:10.1016/j.drudis.2012.07.011