Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
Department of Veterans Affairs, Northern California Healthcare System, Sacramento, CA 95652, USA.
Int J Mol Sci. 2024 Jul 18;25(14):7866. doi: 10.3390/ijms25147866.
Current treatments for lymphoma are plagued by substantial toxicity and the inability to overcome drug resistance, leading to eventual relapse and rationalizing the development of novel, less toxic therapeutics and drug combinations. Histone deacetylase inhibitors (HDACis) are a broad class of epigenetic modulators that have been studied in multiple tumor types, including lymphoma. Currently, HDACis are FDA-approved for treating relapsed T-cell lymphomas and multiple myeloma, with ongoing trials in other lymphomas and solid tumors. As single agents, HDACis frequently elicit toxic side effects and have limited efficacy; therefore, many current treatment strategies focus on combinations to boost efficacy while attempting to minimize toxicity. Fermented wheat germ extract (FWGE) is a complementary agent that has shown efficacy in several malignancies, including lymphoma. Here, we utilize a more potent FWGE derivative, known as fermented wheat germ protein (FWGP), in combination with the HDACi AR42, to assess for enhanced activity. We report increased in vitro killing, cell cycle arrest, and in vivo efficacy for this combination compared to each agent alone with minimal toxicity, suggesting a potentially new, minimally toxic treatment modality for lymphoma.
目前的淋巴瘤治疗方法存在严重的毒性问题，并且无法克服耐药性，导致最终复发，因此需要开发新型、毒性更低的治疗方法和药物组合。组蛋白去乙酰化酶抑制剂（HDACi）是一类广泛的表观遗传调节剂，已在多种肿瘤类型中进行了研究，包括淋巴瘤。目前，HDACi 已获得 FDA 批准用于治疗复发性 T 细胞淋巴瘤和多发性骨髓瘤，并且正在其他淋巴瘤和实体瘤中进行临床试验。作为单一药物，HDACi 经常引起毒性副作用，疗效有限；因此，许多当前的治疗策略侧重于联合用药，以提高疗效，同时尽量减少毒性。发酵小麦胚芽提取物（FWGE）是一种已在多种恶性肿瘤中显示出疗效的辅助药物，包括淋巴瘤。在这里，我们使用一种更有效的 FWGE 衍生物，称为发酵小麦胚芽蛋白（FWGP），与 HDACi AR42 联合使用，以评估增强的活性。我们报告称，与单独使用每种药物相比，这种组合在体外杀伤、细胞周期停滞和体内疗效方面都有所提高，而毒性最小，这表明对于淋巴瘤来说，这是一种潜在的新型、毒性更小的治疗方式。
