Research Papers:

This article has an addendum. Addendum in: Oncotarget. 2023; 14:722-722.

LP-284, a small molecule acylfulvene, exerts potent antitumor activity in preclinical non-Hodgkin's lymphoma models and in cells deficient in DNA damage repair

Jianli Zhou _, Drew Sturtevant, Cassie Love, Aditya Kulkarni, Neha Biyani, Umesh Kathad, Elizabeth Thacker, Sandeep Dave and Kishor Bhatia

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Oncotarget. 2023; 14:597-611. https://doi.org/10.18632/oncotarget.28454

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Jianli Zhou1, Drew Sturtevant1, Cassie Love2, Aditya Kulkarni1, Neha Biyani1, Umesh Kathad1, Elizabeth Thacker3, Sandeep Dave2 and Kishor Bhatia1

1 Lantern Pharma Inc., Plano, TX 75024, USA

2 Department of Medicine, Duke University, Durham, NC 27708, USA

3 Data Driven Bioscience, Durham, NC 27707, USA

Correspondence to:

Jianli Zhou, email: [email protected]

Keywords: non-Hodgkin's lymphoma; DNA damage; homologous recombination repair; transcription-coupled nucleotide excision repair; ATM

Received: May 09, 2023     Accepted: June 01, 2023     Published: June 12, 2023

Copyright: © 2023 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Despite advances in therapies treating non-Hodgkin’s lymphoma (NHL), 20~40% of patients experience relapsed or refractory disease. While solid tumors with homologous recombination deficiencies have been successfully targeted with synthetic lethal agents such as poly-ADP ribose polymerase (PARP) inhibitors, such synthetic lethality strategy has not yet been approved to treat patients with NHL. Here we investigated the mechanism of action (MoA) and therapeutic potential of a new-generation acylfulvene compound, LP-284, in both in vitro and in vivo NHL models. One of LP-284’s MoA includes inducing the repair of double-strand DNA break (DSB). We found that LP-284 exerts nanomolar potency in a panel of hematological cancer cell lines including fifteen NHL cell lines. In vivo, LP-284 treatment prolongs the survival of mantle cell lymphoma (MCL) cell line JeKo-1 derived xenograft mice by two-fold and shows increased efficacy over bortezomib and ibrutinib. In addition, LP-284 is capable of inhibiting tumor growth of JeKo-1 xenografts that are refractory to bortezomib or ibrutinib. We further showed that LP-284 is particularly lethal in cells with deficient DNA damage response and repair, a targetable vulnerability in NHL.

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