The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma
Open accessAbstract
Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor–associated protein CD79B. CD79B-mutant PCNSLs showed enrichment of mammalian target of rapamycin (mTOR)-related gene sets and increased staining with PI3K/mTOR activation markers. Inhibition of the PI3K isoforms p110α/p110δ or mTOR synergized with ibrutinib to induce cell death in CD79B-mutant PCNSL cells. Significance: Ibrutinib has substantial activity in patients with relapsed or refractory B-cell lymphoma of the CNS. Response rates in PCNSL were considerably higher than reported for diffuse large B-cell lymphoma outside the CNS, suggesting a divergent molecular pathogenesis. Combined inhibition of BTK and PI3K/mTOR may augment the ibrutinib response in CD79B-mutant human PCNSLs. Cancer Discov; 7(9); 1018–29. ©2017 AACR. See related commentary by Lakshmanan and Byrd, p. 940. This article is highlighted in the In This Issue feature, p. 920
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Schmitz, R., Wright, G. W., Huang, D. W., Johnson, C. A., Phelan, J. D., Wang, J. Q., Roulland, S., Kasbekar, M., Young, R. M., Shaffer, A. L., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1801445 · Cited by 2,241
Role of Bruton’s tyrosine kinase in B cells and malignancies
Pal Singh, S., Dammeijer, F., & Hendriks, R. W. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0779-z · Cited by 726
NF‐κB signaling in inflammation and cancer
Zhang, T., Ma, C., Zhang, Z., Zhang, H., & Hu, H. (2021) · MedComm · doi:10.1002/mco2.104 · Cited by 574
Metadata
- Authors
- Grommes, C., Pastore, A., Palaskas, N., Tang, S. S., Campos, C., Schartz, D., Codega, P., Nichol, D., Clark, O., Hsieh, W.-Y., Rohle, D., Rosenblum, M., Viale, A., Tabar, V. S., Brennan, C. W., Gavrilovic, I. T., Kaley, T. J., Nolan, C. P., Omuro, A., Pentsova, E., Thomas, A. A., Tsyvkin, E., Noy, A., Palomba, M. L., Hamlin, P., Sauter, C. S., Moskowitz, C. H., Wolfe, J., Dogan, A., Won, M., Glass, J., Peak, S., Lallana, E. C., Hatzoglou, V., Reiner, A. S., Gutin, P. H., Huse, J. T., Panageas, K. S., Graeber, T. G., Schultz, N., DeAngelis, L. M., & Mellinghoff, I. K.
- Venue
- Cancer Discovery
- Published
- 2017-08-31
- Volume
- 7
- Issue
- 9
- Pages
- 1018-1029
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2625473279
- Cited by
- 409
- References
- 50
- FWCI
- 21.64
- Type
- journal article
- Language
- en
- Open access
- green
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- Grommes, C., Pastore, A., Palaskas, N., Tang, S. S., Campos, C., Schartz, D., Codega, P., Nichol, D., Clark, O., Hsieh, W.-Y., Rohle, D., Rosenblum, M., Viale, A., Tabar, V. S., Brennan, C. W., Gavrilovic, I. T., Kaley, T. J., Nolan, C. P., Omuro, A., . . . Mellinghoff, I. K. (2017). Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-17-0613
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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