The DOI matches its Crossref record; 116 of the 116 references it cites were found in a registry or an index.
State-of-the-Art Strategies for Targeting RET-Dependent Cancers
Open accessAbstract
Activating receptor tyrosine kinase RET (rarranged during transfection) gene alterations have been identified as oncogenic in multiple malignancies. RET gene rearrangements retaining the kinase domain are oncogenic drivers in papillary thyroid cancer, non–small-cell lung cancer, and multiple other cancers. Activating RET mutations are associated with different phenotypes of multiple endocrine neoplasia type 2 as well as sporadic medullary thyroid cancer. RET is thus an attractive therapeutic target in patients with oncogenic RET alterations. Multikinase inhibitors with RET inhibitor activity, such as cabozantinib and vandetanib, have been explored in the clinic for tumors with activating RET gene alterations with modest clinical efficacy. As a result of the nonselective nature of these multikinase inhibitors, patients had off-target adverse effects, such as hypertension, rash, and diarrhea. This resulted in a narrow therapeutic index of these drugs, limiting ability to dose for clinically effective RET inhibition. In contrast, the recent discovery and clinical validation of highly potent selective RET inhibitors (pralsetinib, selpercatinib) demonstrating improved efficacy and a more favorable toxicity profile are poised to alter the landscape of RET-dependent cancers. These drugs appear to have broad activity across tumors with activating RET alterations. The mechanisms of resistance to these next-generation highly selective RET inhibitors is an area of active research. This review summarizes the current understanding of RET alterations and the state-of-the-art treatment strategies in RET-dependent cancers.
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Cites
Comprehensive molecular profiling of lung adenocarcinoma
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Integrated Genomic Characterization of Papillary Thyroid Carcinoma
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RET, ROS1 and ALK fusions in lung cancer
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Cabozantinib in Progressive Medullary Thyroid Cancer
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Cited by
Ringel, M. D., Sosa, J. A., Baloch, Z., Bischoff, L., Bloom, G., Brent, G. A., Brock, P. L., Chou, R., Flavell, R. R., Goldner, W., et al. (2025) · Thyroid® · doi:10.1177/10507256251363120 · Cited by 710
Fluorine-containing pharmaceuticals approved by the FDA in 2020: Synthesis and biological activity
Yu, Y., Liu, A., Dhawan, G., Mei, H., Zhang, W., Izawa, K., Soloshonok, V. A., & Han, J. (2021) · Chinese Chemical Letters · doi:10.1016/j.cclet.2021.05.042 · Cited by 182
Novel Calcium-Binding Ablating Mutations Induce Constitutive RET Activity and Drive Tumorigenesis
(2022) · doi:10.1158/0008-5472.can-22-0834 · Cited by 6
Metadata
- Authors
- Subbiah, V., Yang, D., Velcheti, V., Drilon, A., & Meric-Bernstam, F.
- Venue
- Journal of Clinical Oncology
- Published
- 2020-04-10
- Volume
- 38
- Issue
- 11
- Pages
- 1209-1221
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W3008903497
- Cited by
- 258
- References
- 116
- FWCI
- 25.63
- Type
- journal article
- Language
- en
- Open access
- green
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