The DOI matches its Crossref record; 144 of the 144 references it cites were found in a registry or an index.
Emerging Paradigms in the Development of Resistance to Tyrosine Kinase Inhibitors in Lung Cancer
Open accessAbstract
The success of tyrosine kinase inhibitors (TKIs) in select patients with non–small-cell lung cancer (NSCLC) has transformed management of the disease, placing new emphasis on understanding the molecular characteristics of tumor specimens. It is now recognized that genetic alterations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) define two unique subtypes of NSCLC that are highly responsive to genotype-directed TKIs. Despite this initial sensitivity, however, the long-term effectiveness of such therapies is universally limited by the development of resistance. Identifying the mechanisms underlying this resistance is an area of intense, ongoing investigation. In this review, we provide an overview of recent experience in the field, focusing on results from preclinical resistance models and studies of patient-derived, TKI-resistant tumor specimens. Although diverse TKI resistance mechanisms have been identified within EGFR-mutant and ALK-positive patients, we highlight common principles of resistance shared between these groups. These include the development of secondary mutations in the kinase target, gene amplification of the primary oncogene, and upregulation of bypass signaling tracts. In EGFR-mutant and ALK-positive patients alike, acquired resistance may also be a dynamic and multifactorial process that may necessitate the use of treatment combinations. We believe that insights into the mechanisms of TKI resistance in patients with EGFR mutations or ALK rearrangements may inform the development of novel treatment strategies in NSCLC, which may also be generalizable to other kinase-driven malignancies.
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Sever, R., & Brugge, J. S. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006098 · Cited by 989
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Cell death-based treatment of lung adenocarcinoma
Denisenko, T. V., Budkevich, I. N., & Zhivotovsky, B. (2018) · Cell Death & Disease · doi:10.1038/s41419-017-0063-y · Cited by 768
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Metadata
- Authors
- Gainor, J. F., & Shaw, A. T.
- Venue
- Journal of Clinical Oncology
- Published
- 2013-11-01
- Volume
- 31
- Issue
- 31
- Pages
- 3987-3996
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2159587676
- Cited by
- 346
- References
- 144
- FWCI
- 27.28
- Type
- journal article
- Language
- en
- Open access
- green
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- Gainor, J. F., & Shaw, A. T. (2013). Emerging Paradigms in the Development of Resistance to Tyrosine Kinase Inhibitors in Lung Cancer. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2012.45.2029
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
