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The novel PI3K-δ inhibitor TGR-1202 enhances Brentuximab Vedotin-induced Hodgkin lymphoma cell death via mitotic arrest

Leukemia volume 30, pages 2402–2405 (2016)Cite this article

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Despite a variety of novel therapeutic options in Hodgkin lymphoma (HL),1 treatment of primary refractory and early-relapsed patients still represents an unmet medical need requiring the development of more effective strategies.2 Brentuximab vedotin (BV) is a first-in-class antibody-drug conjugate that is approved in the United States and the European Union for the treatment of relapsed or refractory HL following the failure of two chemotherapy regimens or autologous stem cell transplant.3 However, the capacity of this drug to induce a long-term disease control is still under investigation, suggesting that combination therapies using molecularly targeted agents with higher efficacy and reduced toxicity are needed.4

The PI3K/Akt/mTOR pathway has a pathogenetic role in HL, providing the rational to target this pathway.5 Of the several PI3K isoforms, PI3K-δ has a significant role in supporting the growth and survival of B-cell malignancies.6 TGR-1202 is a novel, oral, PI3K-δ-specific inhibitor that is currently in clinical development for a variety of hematological malignancies as a single agent and for all types of B-cell malignancies in combination with other agents.7

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Acknowledgements

This work was supported in part by grants from the Ministry of Health (RF #2010-2313979 to CC-S) and the Italian Association for Cancer Research (AIRC, grant #15835 to CC-S and AIRC 5 × 1000 grant #10007 to GI). SLL is supported by Fondazione Umberto Veronesi.

Author contributions

SLL designed the research, performed the experiments, analyzed and interpreted the data and wrote the manuscript; GC performed the experiments and collected the data; GI, LC, PS, AS revised and approved the manuscript; CC-S designed the research, interpreted the data and wrote the manuscript.

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Authors and Affiliations

  1. Department of Oncology and Hematology, Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, Italy

    S L Locatelli, G Careddu, L Castagna, A Santoro & C Carlo-Stella

  2. Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA,

    G Inghirami

  3. Department of Molecular Biotechnology and Health Science and Center for Experimental Research and Medical Studies (CeRMS), University of Torino, Torino, Italy

    G Inghirami

  4. Department of Pathology, and NYU Cancer Center, New York University School of Medicine, New York, NY, USA

    G Inghirami

  5. TG Therapeutics, Inc., New York, NY, USA

    P Sportelli

  6. Humanitas University, Rozzano, Italy

    A Santoro

  7. Department of Medical Biotechnology and Translational Medicine, University of Milano, Milano, Italy

    C Carlo-Stella

Authors
  1. S L Locatelli
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  2. G Careddu
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  3. G Inghirami
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  4. L Castagna
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  5. P Sportelli
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  6. A Santoro
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  7. C Carlo-Stella
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Corresponding authors

Correspondence to S L Locatelli or C Carlo-Stella.

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Competing interests

Peter Sportelli: Employment & Equity Ownership—TG Therapeutics.

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Locatelli, S., Careddu, G., Inghirami, G. et al. The novel PI3K-δ inhibitor TGR-1202 enhances Brentuximab Vedotin-induced Hodgkin lymphoma cell death via mitotic arrest. Leukemia 30, 2402–2405 (2016). https://doi.org/10.1038/leu.2016.224

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