Trastuzumab Deruxtecan, Antibody–Drug Conjugate Targeting HER2, Is Effective in Pediatric Malignancies: A Report by the Pediatric Preclinical Testing Consortium
Open accessAbstract
HER2 is expressed in many pediatric solid tumors and is a target for innovative immune therapies including CAR-T cells and antibody–drug conjugates (ADC). We evaluated the preclinical efficacy of trastuzumab deruxtecan (T-DXd, DS-8201a), a humanized monoclonal HER2-targeting antibody conjugated to a topoisomerase 1 inhibitor, DXd, in patient- and cell line–derived xenograft (PDX/CDX) models. HER2 mRNA expression was determined using RNA-seq and protein expression via IHC across multiple pediatric tumor PDX models. Osteosarcoma (OS), malignant rhabdoid tumor (MRT), and Wilms tumor (WT) models with varying HER2 expression were tested using 10 mice per group. Additional histologies such as Ewing sarcoma (EWS), rhabdomyosarcoma (RMS), neuroblastoma (NB), and brain tumors were evaluated using single mouse testing (SMT) experiments. T-DXd or vehicle control was administered intravenously to mice harboring established flank tumors at a dose of 5 mg/kg on day 1. Event-free survival (EFS) and objective response were compared between treatment and control groups. HER2 mRNA expression was observed across histologies, with the highest expression in WT (median = 22 FPKM), followed by MRT, OS, and EWS. The relationship between HER2 protein and mRNA expression was inconsistent. T-DXd significantly prolonged EFS in 6/7 OS, 2/2 MRT, and 3/3 WT PDX models. Complete response (CR) or maintained CR (MCR) were observed for 4/5 WT and MRT models, whereas stable disease was the best response among OS models. SMT experiments also demonstrated activity across multiple solid tumors. Clinical trials assessing the efficacy of a HER2-directed ADC in pediatric patients with HER2-expressing tumors should be considered.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several emerging immune-based approaches other than immune-checkpoint inhibitors have generated encouraging preclinical results in osteosarcoma.
“although several emerging immune-based approaches other than the use of ICIs have generated encouraging preclinical results 86,87,88,89,91 .”
From Osteosarcoma (2022) · cites this paper as [87]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · see citing works
Coussens, L. M., Yang‐Feng, T. L., Liao, Y.-C., Chen, E., Gray, A., McGrath, J. P., Seeburg, P. H., Libermann, T. A., Schlessinger, J., Francke, U., et al. (1985) · Science · doi:10.1126/science.2999974 · Cited by 1,815 · see citing works
Hirsch, F. R., Varella‐Garcia, M., Bunn, P. A., Maria, M. V. D., Veve, R., Bremnes, R. M., Barón, A. E., Zeng, C., & Franklin, W. A. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.11.069 · Cited by 1,476 · see citing works
Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer
Shitara, K., Bang, Y.-J., Iwasa, S., Sugimoto, N., Ryu, M.-H., Sakai, D., Chung, H.-C., Kawakami, H., Yabusaki, H., Lee, J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2004413 · Cited by 1,333 · see citing works
Guy, C. T., Webster, M. A., Schaller, M. D., Parsons, T. J., Cardiff, R. D., & Muller, W. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.10578 · Cited by 1,193 · see citing works
The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen
Schechter, A. L., Stern, D. F., Vaidyanathan, L., Decker, S. J., Drebin, J. A., Greene, M. I., & Weinberg, R. A. (1984) · Nature · doi:10.1038/312513a0 · Cited by 1,177 · see citing works
erb B-2 Is a Potent Oncogene When Overexpressed in NIH/3T3 Cells
Fiore, P. P. D., Pierce, J. H., Kraus, M. H., Segatto, O., King, C. R., & Aaronson, S. A. (1987) · Science · doi:10.1126/science.2885917 · Cited by 1,011 · see citing works
Ahmed, N., Brawley, V. S., Hegde, M., Robertson, C., Ghazi, A., Gerken, C., Liu, E., Dakhova, O., Ashoori, A., Corder, A., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.58.0225 · Cited by 1,004 · see citing works
Modi, S., Park, H., Murthy, R. K., Iwata, H., Tamura, K., Tsurutani, J., Moreno‐Aspitia, A., Doi, T., Sagara, Y., Redfern, C. H., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.19.02318 · Cited by 788 · see citing works
Hudziak, R. M., Schlessinger, J., & Ullrich, A. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.20.7159 · Cited by 616 · see citing works
Doi, T., Shitara, K., Naito, Y., Shimomura, A., Fujiwara, Y., Yonemori, K., Shimizu, C., Shimoi, T., Kuboki, Y., Matsubara, N., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30604-6 · Cited by 507 · see citing works
The pediatric preclinical testing program: Description of models and early testing results
Houghton, P. J., Morton, C. L., Tucker, C., Payne, D., Favours, E., Cole, C., Gorlick, R., Kolb, E. A., Zhang, W., Lock, R., et al. (2007) · Pediatric Blood & Cancer · doi:10.1002/pbc.21078 · Cited by 480 · see citing works
Self-citationSiena, S., Bartolomeo, M. D., Raghav, K. P. S., Masuishi, T., Loupakis, F., Kawakami, H., Yamaguchi, K., Nishina, T., Fakih, M., Élez, E., et al. (2021) · The Lancet Oncology · doi:10.1016/s1470-2045(21)00086-3 · Cited by 432 · see citing works
Antibody–drug conjugates (ADCs) for cancer therapy: Strategies, challenges, and successes
Abdollahpour‐Alitappeh, M., Lotfinia, M., Gharibi, T., Mardaneh, J., Farhadihosseinabadi, B., Larki, P., Faghfourian, B., Sepehr, K. S., Abbaszadeh‐Goudarzi, K., Abbaszadeh‐Goudarzi, G., et al. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27419 · Cited by 255 · see citing works
Ebb, D., Meyers, P., Grier, H., Bernstein, M., Gorlick, R., Lipshultz, S. E., Krailo, M., Devidas, M., Barkauskas, D. A., Siegal, G. P., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.37.4546 · Cited by 243 · see citing works
Self-citationTakegawa, N., Nonagase, Y., Yonesaka, K., Sakai, K., Maenishi, O., Ogitani, Y., Tamura, T., Nishio, K., Nakagawa, K., & Tsurutani, J. (2017) · International Journal of Cancer · doi:10.1002/ijc.30870 · Cited by 197 · see citing works
Rokita, J. L., Rathi, K. S., Cardenas, M., Upton, K. A., Jayaseelan, J. C., Cross, K. L., Pfeil, J., Egolf, L. E., Way, G. P., Farrel, A., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.071 · Cited by 178 · see citing works
Self-citationNarayan, P., Osgood, C. L., Singh, H., Chiu, H.-J., Ricks, T. K., Chow, E. C. Y., Qiu, J., Song, P., Yu, J., Namuswe, F., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-4557 · Cited by 172 · see citing works
Kendsersky, N. M., Lindsay, J., Kolb, E. A., Smith, M. A., Teicher, B. A., Erickson, S. W., Earley, E. J., Mosse, Y. P., Martinez, D., Pogoriler, J., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-4221 · Cited by 120 · see citing works
Self-citationMolecular Characterization of the Pediatric Preclinical Testing Panel
Neale, G. A. M., Su, X., Morton, C. L., Phelps, D. A., Gorlick, R. G., Lock, R. B., Reynolds, C. P., Maris, J. M., Friedman, H. S., Dome, J. S., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-5090 · Cited by 117 · see citing works
Self-citationOkamoto, H., Oitate, M., Hagihara, K., Shiozawa, H., Furuta, Y., Ogitani, Y., & Kuga, H. (2020) · Xenobiotica · doi:10.1080/00498254.2020.1755909 · Cited by 82 · see citing works
Fouladi, M., Stewart, C. F., Blaney, S. M., Onar‐Thomas, A., Schaiquevich, P. S., Packer, R. J., Gajjar, A. J., Kun, L. E., Boyett, J. M., & Gilbertson, R. J. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.4687 · Cited by 79 · see citing works
Evaluation of Alternative <i>In Vivo</i> Drug Screening Methodology: A Single Mouse Analysis
Murphy, B., Yin, H., Maris, J. M., Kolb, E. A., Gorlick, R., Reynolds, C. P., Kang, M. H., Keir, S. T., Kurmasheva, R. T., Dvorchik, I., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0122 · Cited by 69 · see citing works
Self-citationFouladi, M., Stewart, C. F., Blaney, S. M., Onar‐Thomas, A., Schaiquevich, P. S., Packer, R. J., Goldman, S., Geyer, J. R., Gajjar, A. J., Kun, L. E., et al. (2013) · Journal of Neuro-Oncology · doi:10.1007/s11060-013-1166-7 · Cited by 67 · see citing works
DeWire, M. D., Fouladi, M., Turner, D. C., Wetmore, C., Hawkins, C. E., Jacob, C., Yuan, Y., Liu, D., Goldman, S., Fisher, P. G., et al. (2015) · Journal of Neuro-Oncology · doi:10.1007/s11060-015-1764-7 · Cited by 67 · see citing works
Hingorani, P., Roth, M. E., Wang, Y., Zhang, W., Gill, J. B., Harrison, D. J., Teicher, B., Erickson, S., Gatto, G., Smith, M. A., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0406 · Cited by 41 · see citing works
Self-citationErbB2 IS A TUMOR ASSOCIATED ANTIGEN AND A SUITABLE THERAPEUTIC TARGET IN WILMS TUMOR
Pinthus, J. H., Fridman, E., Dekel, B., Goldberg, I., Kaufman‐Francis, K., Eshhar, Z., Harmelin, A., Rechavi, G., Mor, O., Ramon, J., et al. (2004) · The Journal of Urology · doi:10.1097/01.ju.0000140139.91993.a0 · Cited by 27 · see citing works
Association between the HER2 expression and histological differentiation in Wilms tumor
Salem, M. L., Kinoshita, Y., Tajiri, T., Souzaki, R., Tatsuta, K., Higashi, M., Izaki, T., Kohashi, K., Tsuneyoshi, M., & Taguchi, T. (2006) · Pediatric Surgery International · doi:10.1007/s00383-006-1762-0 · Cited by 24 · see citing works
Prospective use of the single-mouse experimental design for the evaluation of PLX038A
Ghilu, S., Li, Q., Fontaine, S. D., Santi, D. V., Kurmasheva, R. T., Zheng, S., & Houghton, P. J. (2020) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-019-04017-8 · Cited by 20 · see citing works
Self-citationHER2/neu Expression: A Predictor for Differentiation and Survival in Children With Wilms Tumor
Ragab, S. M., Samaka, R. M., & Shams, T. M. (2009) · Pathology & Oncology Research · doi:10.1007/s12253-009-9188-3 · Cited by 16 · see citing works
Preclinical Childhood Sarcoma Models: Drug Efficacy Biomarker Identification and Validation
Geier, B., Kurmashev, D., Kurmasheva, R. T., & Houghton, P. J. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00193 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Beird, H. C., Bielack, S. S., Flanagan, A. M., Gill, J., Heymann, D., Janeway, K. A., Livingston, J. A., Roberts, R. D., Strauss, S. J., & Gorlick, R. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00409-y · Cited by 660 · see citing works
Self-citationChildren's Oncology Group's 2023 blueprint for research: Renal tumors
Geller, J. I., Hong, A. L., Vallance, K., Evageliou, N., Aldrink, J. H., Cost, N. G., Treece, A. L., Renfro, L. A., & Mullen, E. A. (2023) · Pediatric Blood & Cancer · doi:10.1002/pbc.30586 · Cited by 34 · see citing works
Unraveling molecular aberrations and pioneering therapeutic strategies in osteosarcoma
Yan, P., Wang, J., Yue, B., & Wang, X. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189171 · Cited by 31 · see citing works
HER2 Antibody–Drug Conjugates Are Active against Desmoplastic Small Round Cell Tumor
Zhang, T., Febres‐Aldana, C. A., Liu, Z., Dix, J.-M., Cheng, R., Dematteo, R. G., Lui, A. J. W., Khodos, I., Gili, L., Mattar, M. S., et al. (2024) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-1835 · Cited by 23 · see citing works
Magrath, J. W., Espinosa-Cotton, M. M., Flinchum, D. A., Sampath, S. S., Cheung, N. V., & Lee, S. B. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1442488 · Cited by 21 · see citing works
Lessons learned from 20 years of preclinical testing in pediatric cancers
Smith, M. A., Houghton, P. J., Lock, R. B., Maris, J. M., Gorlick, R. G., Kurmasheva, R. T., Li, X., Teicher, B. A., Chuang, J. H., Cruz, F. S. D., et al. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108742 · Cited by 19 · see citing works
Self-citationOsteosarcoma through the Lens of Bone Development, Signaling, and MicroenvironmentPreprint
Young, E. P., Marinoff, A. E., López-Fuentes, E., & Sweet-Cordero, A. (2024) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041635 · Cited by 14 · see citing works
Nakano, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242316823 · Cited by 14 · see citing works
Тодосенко, Н. М., Хлусов, И. А., Yurova, K. A., Геннадьевна, Х. О., & Litvinova, L. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108993 · Cited by 12 · see citing works
Bianchi, G., Pastorino, F., Rolandi, G., Ciampi, E., Segalerba, D., Giovanni, B. D., Cafferata, B., Balbi, M., Ravera, S., Vellone, V. G., et al. (2026) · Cell Death and Disease · doi:10.1038/s41419-025-08397-z · Cited by 7 · see citing works
Sutton, K. S., Walz, A. L., Groenendijk, A., Murphy, A. J., Pater, L. E., Janssens, G. O. R. J., Brzezinski, J. J., Mullen, E. A., Spreafico, F., Godzinski, J. K., et al. (2025) · Pediatric Blood & Cancer · doi:10.1002/pbc.31790 · Cited by 5 · see citing works
Establishment of Patient-derived Xenograft Mouse Model with Human Osteosarcoma Tissues
Sun, X., Chang, J., Zhou, C., Zhao, P., Guo, S., Tong, J., Wang, Y., & Yang, Y. (2024) · Journal of Visualized Experiments · doi:10.3791/66491 · Cited by 3 · see citing works
Self-citationAdoptive Cell Therapy for Pediatric Solid TumorsPreprint
Hont, A. B., & Bollard, C. M. (2025) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041636 · Cited by 3 · see citing works
Donzé, C., Hamani, A., Revon‐Rivière, G., Filaine, P., & André, N. (2025) · Pediatric Blood & Cancer · doi:10.1002/pbc.32009 · Cited by 2 · see citing works
Reed, D. R., Janeway, K. A., Minard, C. G., Hall, D. C., Crompton, B. D., Lazar, A. J., Wang, W., Zylber, R. J., Contreras, A., Carrero, G., et al. (2025) · JCO oncology advances. · doi:10.1200/oa-25-00094 · Cited by 3 · see citing works
Self-citationTrastuzumab Deruxtecan Is Active in Desmoplastic Small Round Cell Tumor
Slotkin, E. K., Feinberg, T. Y., Bhanot, U. K., Price, A. P., Pandit-Taskar, N. D., Domenico, D., Behr, G., Agaram, N. P., Antonescu, C. R., Hameed, M., et al. (2026) · JCO oncology advances. · doi:10.1200/oa-25-00141 · Cited by 2 · see citing works
Rhabdomyosarcoma: development of molecular therapeutics under the microscope
Houghton, P. J., & Bjornsti, M. (2025) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2025.2551106 · Cited by 2 · see citing works
Self-citationCharlab, R., Leong, R., Shord, S. S., & Reaman, G. H. (2024) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041656 · Cited by 2 · see citing works
Szabo, D. J., Toth, E., Szabó, K., Hegedüs, Z., Bózsity, N., Zupkó, I., Rovó, L., Xiao, X., Xu, L., & Keller-Pintér, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26052137 · Cited by 1 · see citing works
Emerging interventional treatments in the management of pediatric brain tumors
Shatara, M., Ho, W. S., Roland, J. L., & Limbrick, D. D. (2025) · Advances in cancer research · doi:10.1016/bs.acr.2025.09.004 · Cited by 1 · see citing works
Haney, S. L., & Holstein, S. A. (2025) · Cancer Reports · doi:10.1002/cnr2.70390 · Cited by 1 · see citing works
Ortiz, M. V., Wens, F. S. P. L., Hong, A. L., Quarello, P., Verschuur, A. C., Tracy, E. T., Daw, N. C., Dome, J. S., Walz, A. L., Sprokkerieft, J., et al. (2026) · Nature Reviews Urology · doi:10.1038/s41585-025-01117-4 · Cited by 1 · see citing works
An, B., Hu, Y., & Liang, X. (2022) · Genetics Research · doi:10.1155/2022/2365991
Patel, K. R., Espinoza, A. F., Urbicain, M., Patel, R. H., Major, A. M., Sarabia, S. F., Lopez-Terrada, D. H., Vasudevan, S. A., & Woodfield, S. E. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155163
Guo, P., Li, Y., Huang, J., Jin, L., Liu, X., He, D., & Moses, M. A. (2025) · Advanced Therapeutics · doi:10.1002/adtp.202400423
Keck, J. M., Zhu, L., Stommel, J. M., Egger, J., Ozmen, T. Y., Ozmen, F., Lee, J., Tate, B. J., Rames, M. J., Creason, A., et al. (2026) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-25-1134
Yang, Y., Xing, Y., Zhang, J., Dai, Y., Ma, L. B., Yang, T., Li, Y., Li, Y., Zhang, J., Wang, Y., et al. (2026) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2026.09.005
Self-citationLehtolainen‐Dalkilic, P., Concannon, C. G., Karres, D., Peirs, S., Pirotte, E., Miermont, A., Lavergne, F., van Meer, P., Sheean, M. E., & Malderen, K. V. (2026) · EJC Paediatric Oncology · doi:10.1016/j.ejcped.2026.100556
- Authors
- Hingorani, P., Zhang, W., Zhang, Z., Xu, Z., Wang, W.-L., Roth, M. E., Wang, Y., Gill, J. B., Harrison, D. J., Teicher, B. A., Erickson, S. W., Gatto, G., Kolb, E. A., Smith, M. A., Kurmasheva, R. T., Houghton, P. J., & Gorlick, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- National Cancer Institute (US)
- RTI International (US)
- Alfred I. duPont Hospital for Children (US)
- 6Greehey Children's Research Cancer Institute, San Antonio, Texas.
- Corresponding author
- Hingorani, Pooja
- Gorlick, Richard
- ORCID
- Venue
- Molecular Cancer Therapeutics
- Published
- 2022-06-02
- Volume
- 21
- Issue
- 8
- Pages
- 1318-1325
- ISSN
- 1535-7163 (ISSN-L)
- 1538-8514
- OpenAlex
- W4282921745
- Cited by
- 28
- References
- 31
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 8 · 2023: 3 · 2022: 2
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- Molecular Cancer Therapeutics (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- NCI (5U01CA199221, 5UO1CA199297)
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- trastuzumab deruxtecan, HER2, antibody-drug conjugates, pediatric solid tumors, osteosarcoma, malignant rhabdoid tumor, Wilms tumor, Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, brain tumors, topoisomerase I inhibitor, HER2 mRNA expression, event-free survival
- MeSH terms
- Trastuzumab, Animals, Camptothecin, Humans, Neoplasms, RNA, Messenger, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Immunoconjugates, Mice, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
