The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Targeting HER2-Positive Breast Cancer with Trastuzumab-DM1, an Antibody–Cytotoxic Drug Conjugate
Abstract
HER2 is a validated target in breast cancer therapy. Two drugs are currently approved for HER2-positive breast cancer: trastuzumab (Herceptin), introduced in 1998, and lapatinib (Tykerb), in 2007. Despite these advances, some patients progress through therapy and succumb to their disease. A variation on antibody-targeted therapy is utilization of antibodies to deliver cytotoxic agents specifically to antigen-expressing tumors. We determined in vitro and in vivo efficacy, pharmacokinetics, and toxicity of trastuzumab-maytansinoid (microtubule-depolymerizing agents) conjugates using disulfide and thioether linkers. Antiproliferative effects of trastuzumab-maytansinoid conjugates were evaluated on cultured normal and tumor cells. In vivo activity was determined in mouse breast cancer models, and toxicity was assessed in rats as measured by body weight loss. Surprisingly, trastuzumab linked to DM1 through a nonreducible thioether linkage (SMCC), displayed superior activity compared with unconjugated trastuzumab or trastuzumab linked to other maytansinoids through disulfide linkers. Serum concentrations of trastuzumab-MCC-DM1 remained elevated compared with other conjugates, and toxicity in rats was negligible compared with free DM1 or trastuzumab linked to DM1 through a reducible linker. Potent activity was observed on all HER2-overexpressing tumor cells, whereas nontransformed cells and tumor cell lines with normal HER2 expression were unaffected. In addition, trastuzumab-DM1 was active on HER2-overexpressing, trastuzumab-refractory tumors. In summary, trastuzumab-DM1 shows greater activity compared with nonconjugated trastuzumab while maintaining selectivity for HER2-overexpressing tumor cells. Because trastuzumab linked to DM1 through a nonreducible linker offers improved efficacy and pharmacokinetics and reduced toxicity over the reducible disulfide linkers evaluated, trastuzumab-MCC-DM1 was selected for clinical development. [Cancer Res 2008;68(22):9280–90]
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Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer
Piccart-Gebhart, M. J., Procter, M., Leyland-Jones, B., Goldhirsch, A., Untch, M., Smith, I., Gianni, L., Baselga, J., Bell, R., Jackisch, C., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa052306 · Cited by 5,084
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Biosynthesis of tumorigenic HER2 C-terminal fragments by alternative initiation of translation
Anido, J., Scaltriti, M., Bech Serra, J. J., Josefat, B. S., Rojo Todo, F., Baselga, J., & Arribas, J. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601191 · Cited by 231
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Self-citationFinkle, D., Quan, Z. R., Asghari, V., Kloss, J., Ghaboosi, N., Mai, E., Wong, W. L., Hollingshead, P., Schwall, R., Koeppen, H., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-03-0448 · Cited by 125
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Verma, S., Miles, D., Gianni, L., Krop, I. E., Welslau, M., Baselga, J., Pegram, M., Oh, D.-Y., Diéras, V., Guardino, E., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1209124 · Cited by 3,834
Engineered Nanoparticles for Drug Delivery in Cancer Therapy
Sun, T., Zhang, Y. S., Pang, B., Hyun, D. C., Yang, M., & Xia, Y. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201403036 · Cited by 2,164
Antibody drug conjugate: the “biological missile” for targeted cancer therapy
Fu, Z., Li, S., Han, S., Shi, C., & Zhang, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00947-7 · Cited by 1,643
Targeting HER2-positive breast cancer: advances and future directions
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Metadata
- Authors
- Lewis Phillips, G. D., Li, G., Dugger, D. L., Crocker, L. M., Parsons, K. L., Mai, E., Blättler, W. A., Lambert, J. M., Chari, R. V. J., Lutz, R. J., Wong, W. L. T., Jacobson, F. S., Koeppen, H., Schwall, R. H., Kenkare-Mitra, S. R., Spencer, S. D., & Sliwkowski, M. X.
- Venue
- Cancer Research
- Published
- 2008-11-14
- Volume
- 68
- Issue
- 22
- Pages
- 9280-9290
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W1984007340
- Cited by
- 1,676
- References
- 7
- FWCI
- 24.79
- Type
- journal article
- Language
- en
- Open access
- closed
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- Lewis Phillips, G. D., Li, G., Dugger, D. L., Crocker, L. M., Parsons, K. L., Mai, E., Blättler, W. A., Lambert, J. M., Chari, R. V. J., Lutz, R. J., Wong, W. L. T., Jacobson, F. S., Koeppen, H., Schwall, R. H., Kenkare-Mitra, S. R., Spencer, S. D., & Sliwkowski, M. X. (2008). Targeting HER2-Positive Breast Cancer with Trastuzumab-DM1, an Antibody–Cytotoxic Drug Conjugate. Cancer Research. https://doi.org/10.1158/0008-5472.can-08-1776
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