The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers
Open accessAbstract
Amplification of and oncogenic mutations in ERBB2, the gene encoding the HER2 receptor tyrosine kinase, promote receptor hyperactivation and tumor growth. Here we demonstrate that HER2 ubiquitination and internalization, rather than its overexpression, are key mechanisms underlying endocytosis and consequent efficacy of the anti-HER2 antibody–drug conjugates (ADC) ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in lung cancer cell lines and patient-derived xenograft models. These data translated into a 51% response rate in a clinical trial of T-DM1 in 49 patients with ERBB2-amplified or -mutant lung cancers. We show that cotreatment with irreversible pan-HER inhibitors enhances receptor ubiquitination and consequent ADC internalization and efficacy. We also demonstrate that ADC switching to T-DXd, which harbors a different cytotoxic payload, achieves durable responses in a patient with lung cancer and corresponding xenograft model developing resistance to T-DM1. Our findings may help guide future clinical trials and expand the field of ADC as cancer therapy. Significance: T-DM1 is clinically effective in lung cancers with amplification of or mutations in ERBB2. This activity is enhanced by cotreatment with irreversible pan-HER inhibitors, or ADC switching to T-DXd. These results may help address unmet needs of patients with HER2-activated tumors and no approved targeted therapy. See related commentary by Rolfo and Russo, p. 643. This article is highlighted in the In This Issue feature, p. 627
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Cites
Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732
Trastuzumab deruxtecan in previously treated HER2-positive breast cancer
Modi, S., Saura, C., Yamashita, T., Park, Y. H., Kim, S.-B., Tamura, K., Andre, F., Iwata, H., Ito, Y., Tsurutani, J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1914510 · Cited by 2,006
Self-citationTucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer
Murthy, R. K., Loi, S., Okines, A., Paplomata, E., Hamilton, E., Hurvitz, S. A., Lin, N. U., Borges, V., Abramson, V., Anders, C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1914609 · Cited by 1,326
Self-citationERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics
Arteaga, C. L., & Engelman, J. A. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.025 · Cited by 1,048
HER kinase inhibition in patients with HER2- and HER3-mutant cancers
Hyman, D. M., Piha-Paul, S. A., Won, H., Rodon, J., Saura, C., Shapiro, G. I., Juric, D., Quinn, D. I., Moreno, V., Doger, B., et al. (2018) · Nature · doi:10.1038/nature25475 · Cited by 780
Self-citationJordan, E. J., Kim, H. R., Arcila, M. E., Barron, D., Chakravarty, D., Gao, J., Chang, M. T., Ni, A., Kundra, R., Jonsson, P., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1337 · Cited by 643
Self-citationRobichaux, J. P., Elamin, Y. Y., Vijayan, R. S. K., Nilsson, M. B., Hu, L., He, J., Zhang, F., Pisegna, M., Poteete, A., Sun, H., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.09.001 · Cited by 242
Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads
Nakada, T., Masuda, T., Naito, H., Yoshida, M., Ashida, S., Morita, K., Miyazaki, H., Kasuya, Y., Ogitani, Y., Yamaguchi, J., et al. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.02.020 · Cited by 172
Cited by
Thai, A. A., Solomon, B. J., Sequist, L. V., Gainor, J. F., & Heist, R. S. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00312-3 · Cited by 2,576
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., Saltos, A. N., Felip, E., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2112431 · Cited by 1,021
Self-citationOvercoming therapy resistance in EGFR-mutant lung cancer
Passaro, A., Jänne, P. A., Mok, T., & Peters, S. (2021) · Nature Cancer · doi:10.1038/s43018-021-00195-8 · Cited by 565
Goto, K., Goto, Y., Kubo, T., Ninomiya, K., Kim, S.-W., Planchard, D., Ahn, M.-J., Smit, E. F., de Langen, A. J., Pérol, M., et al. (2023) · Journal of Clinical Oncology · doi:10.1200/jco.23.01361 · Cited by 328
The Journey of Antibody–Drug Conjugates: Lessons Learned from 40 Years of Development
Colombo, R., Tarantino, P., Rich, J. R., LoRusso, P. M., & de Vries, E. G. E. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0708 · Cited by 254
Metadata
- Authors
- Li, B. T., Michelini, F., Misale, S., Cocco, E., Baldino, L., Cai, Y., Shifman, S., Tu, H.-Y., Myers, M. L., Xu, C., Mattar, M., Khodos, I., Little, M., Qeriqi, B., Weitsman, G., Wilhem, C. J., Lalani, A. S., Diala, I., Freedman, R. A., Lin, N. U., Solit, D. B., Berger, M. F., Barber, P. R., Ng, T., Offin, M., Isbell, J. M., Jones, D. R., Yu, H. A., Thyparambil, S., Liao, W.-L., Bhalkikar, A., Cecchi, F., Hyman, D. M., Lewis, J. S., Buonocore, D. J., Ho, A. L., Makker, V., Reis-Filho, J. S., Razavi, P., Arcila, M. E., Kris, M. G., Poirier, J. T., Shen, R., Tsurutani, J., Ulaner, G. A., de Stanchina, E., Rosen, N., Rudin, C. M., & Scaltriti, M.
- Venue
- Cancer Discovery
- Published
- 2020-05-01
- Volume
- 10
- Issue
- 5
- Pages
- 674-687
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W3013150216
- Cited by
- 288
- References
- 8
- FWCI
- 11.63
- Type
- journal article
- Language
- en
- Open access
- green
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- Li, B. T., Michelini, F., Misale, S., Cocco, E., Baldino, L., Cai, Y., Shifman, S., Tu, H.-Y., Myers, M. L., Xu, C., Mattar, M., Khodos, I., Little, M., Qeriqi, B., Weitsman, G., Wilhem, C. J., Lalani, A. S., Diala, I., Freedman, R. A., . . . Scaltriti, M. (2020). HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-20-0215
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