The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity
Open accessAbstract
We characterized the landscape and drug sensitivity of ERBB2 (HER2) mutations in cancers. In 11 datasets (n = 211,726), ERBB2 mutational hotspots varied across 25 tumor types. Common HER2 mutants yielded differential sensitivities to eleven EGFR/HER2 tyrosine kinase inhibitors (TKIs) in vitro, and molecular dynamics simulations revealed that mutants with a reduced drug-binding pocket volume were associated with decreased affinity for larger TKIs. Overall, poziotinib was the most potent HER2 mutant-selective TKI tested. Phase II clinical testing in ERBB2 exon 20-mutant non-small cell lung cancer resulted in a confirmed objective response rate of 42% in the first 12 evaluable patients. In pre-clinical models, poziotinib upregulated HER2 cell-surface expression and potentiated the activity of T-DM1, resulting in complete tumor regression with combination treatment.
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“Clinically, second-generation TKIs have been associated with inhibition of wild-type EGFR and related adverse events15,35,36; however, most second-generation TKIs are dosed at the maximum tolerated doses, resulting in plasma concentrations 10–100 fold greater than concentrations necessary for inhibiting PACC mutations.”
From Structure-based classification predicts drug response in EGFR-mutant NSCLC (2021) · cites this paper as [36]
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Trastuzumab Deruxtecan in HER2 -Mutant Non–Small-Cell Lung Cancer
Li, B. T., Smit, E. F., Goto, Y., Nakagawa, K., Udagawa, H., Mazières, J., Nagasaka, M., Bazhenova, L. A., Saltos, A. N., Felip, E., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2112431 · Cited by 1,068
Structure-based classification predicts drug response in EGFR-mutant NSCLC
Robichaux, J. P., Le, X., Vijayan, R. S. K., Hicks, J. K., Heeke, S., Elamin, Y. Y., Lin, H. Y., Udagawa, H., Skoulidis, F., Tran, H., et al. (2021) · Nature · doi:10.1038/s41586-021-03898-1 · Cited by 490
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HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers
Li, B. T., Michelini, F., Misale, S., Cocco, E., Baldino, L., Cai, Y., Shifman, S. G., Tu, H., Myers, M. L., Xu, C., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0215 · Cited by 293
Endocytosis in cancer and cancer therapy
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Metadata
- Authors
- Robichaux, J. P., Elamin, Y. Y., Vijayan, R. S. K., Nilsson, M. B., Hu, L., He, J., Zhang, F., Pisegna, M., Poteete, A., Sun, H., Li, S., Chen, T., Han, H., Negrao, M. V., Ahnert, J. R., Diao, L., Wang, J., Le, X., Meric-Bernstam, F., Routbort, M., Roeck, B., Yang, Z., Raymond, V. M., Lanman, R. B., Frampton, G. M., Miller, V. A., Schrock, A. B., Albacker, L. A., Wong, K.-K., Cross, J. B., & Heymach, J. V.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- NYU Langone Health (US)
- Spectrum Pharmaceuticals (United States) (US)
- Guardant (United States) (US)
- Foundation Medicine (United States) (US)
- Corresponding author
- Heymach, John V.
- ORCID
- Robichaux, Jacqulyne P.
- Elamin, Yasir Y.
- Vijayan, R.S.K.
- Nilsson, Monique B.
- He, Junqin
- Zhang, Fahao
- Poteete, Alissa
- Sun, Huiying
- Li, Shuai
- Chen, Ting
- Han, Han
- Negrao, Marcelo Vailati
- Diao, Lixia
- Wang, Jing
- Le, Xiuning
- Raymond, Victoria M.
- Lanman, Richard B.
- Frampton, Garrett M.
- Miller, Vincent A.
- Schrock, Alexa B.
- Albacker, Lee A.
- Wong, Kwok-kin
- Cross, Jason B.
- Heymach, John V.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 36
- Issue
- 4
- Pages
- 444-457.e7
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC6944069
- OpenAlex
- W2977889895
- Cited by
- 242
- References
- 66
- Citations by year
- 2026: 21 · 2025: 34 · 2024: 33 · 2023: 40 · 2022: 43 · 2021: 43 · 2020: 28
- FWCI
- 12.00
- Type
- journal article
- Language
- en
- Update notices
- erratum (2020-03-16)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- ERBB2 mutations, HER2, poziotinib, tyrosine kinase inhibitors, trastuzumab emtansine, non-small cell lung cancer, drug sensitivity, molecular dynamics simulation, drug-binding pocket, combination therapy
- MeSH terms
- Antineoplastic Agents, Immunological, Progression-Free Survival, Ado-Trastuzumab Emtansine, Adult, Animals, Antineoplastic Combined Chemotherapy Protocols, Disease Models, Animal, DNA Mutational Analysis, Drug Synergism, Female, Humans, Male, Mice, Transgenic, Mutation, Neoplasms, Quinazolines, Erb-b2 Receptor Tyrosine Kinases, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, Mice, Datasets as Topic
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