Drug resistance to targeted therapeutic strategies in non-small cell lung cancer

Publication date: Available online 9 November 2019Source: Pharmacology &TherapeuticsAuthor(s): Wen-juan Liu, Yue Du, Ru Wen, Ming Yang, Jian XuAbstractRapidly developing molecular biology techniques have been employed to identify cancer driver genes in specimens from patients with non-small cell lung cancer (NSCLC). Inhibitors and antibodies that specifically target driver gene-mediated signaling pathways to suppress tumor growth and progression are expected to extend the survival time and further improve the quality of life of patients. However, the health of patients with advanced and metastatic NSCLC presents significant challenges due to treatment resistance, mediated by cancer driver gene alteration, epigenetic alteration, and tumor heterogeneity. In this review, we discuss two different resistance mechanisms in NSCLC targeted therapies, namely changes in the targeted oncogenes (on-target resistance) and changes in other related signaling pathways (off-target resistance) in tumor cells. We highlight the conventional mechanisms of drug resistance elicited by the complex heterogeneous microenvironment of NSCLC during targeted therapy, including mutations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), the receptor tyrosine kinase ROS proto-oncogene 1 (ROS1), and the serine/threonine-protein kinase BRAF (v-Raf murine sarcoma viral oncogene homolog B). We also discuss the mechanism of action of less common oncoproteins, as in-depth understan...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research

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Source: Nutrition and Cancer - Category: Cancer & Oncology Authors: Tags: Nutr Cancer Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research
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Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
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