Journal
PHARMACOLOGY & THERAPEUTICS
Volume 202, Issue -, Pages 140-148Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2019.06.005
Keywords
Non-small lung Cancer (NSCLC); Therapeutic regimen; Drug resistance; Genetic alteration
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Funding
- PO FESR 2014-2020-Campania Oncotherapies
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The discovery of genetic alterations, that can be targeted therapeutically, has launched a new era for lung cancer research and personalized therapy. However, not all the identified new genetic driver mutations are therapeutically targetable due to high toxicity profile. On the other hand, those genetic alterations that could be pharmacologically targeted, are often subject of alternative mutations that lead to drug resistance, which represents one of the major clinical limitation. Mechanisms of acquired resistance in oncogene-driven malignancies occur after additional genetic alterations of the primary oncogene. In this scenario, the secondary genetic alteration can lead to up-regulation of bypass-signaling pathways, changes in tumor histology or alterations in drug metabolism, that are able to promote drug resistance with an ensuing lower survival rate of the patient. Another aspect to be considered is that non-genetically mutated patients still have poor pharmacological options and therefore still represent an unmet medical need. Therefore, identifying mechanisms underlying both drug resistance in genetically mutated patients and novel therapeutic alternatives for non-mutated NSCLC patients is still an area of intense investigation. (C) 2019 Published by Elsevier Inc.
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