Pi Manfei, Kuang Huixian, Yue Chunyan, Yang Qixuan, Wu Anqin, Li Yuhua, Assaraf Yehuda G, Yang Dong-Hua, Wu Shaojie
Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
The Fred Wyszkowski Cancer Research Lab, Technion - Israel Institute of Technology, Haifa, Israel.
Drug Resist Updat. 2022 Mar;61:100822. doi: 10.1016/j.drup.2022.100822. Epub 2022 Mar 4.
Cancer cell metabolism including aerobic glycolysis, amino acid and fatty acid metabolism, has been extensively studied. Metabolic reprogramming is a major hallmark of cancer, which promotes cancer cell proliferation, progression and metastasis, as well as provokes resistance to chemotherapeutic drugs. Several signal transduction pathways, such as BCR, MEK/ERK, Notch, NF-κB and PI3K/AKT/mTOR, regulate tumor metabolism, hence promoting tumor cell growth, proliferation and progression. Therefore, targeting metabolic enzymes, metabolites or their signal transduction pathways may constitute a promising therapeutic strategy to enhance cancer treatment efficacy. Diffuse large B-cell lymphoma (DLBCL) is the most aggressive form of non-Hodgkin lymphoma (NHL), and one-third of DLBCL patients suffer from relapsed/refractory disease after chemotherapy. The mechanisms underlying drug resistance are complex, including target gene mutations, metabolic reprogramming, aberrant signal transduction pathways, enhanced drug efflux via overexpression of multidrug efflux transporters like P-glycoprotein, upregulation of anti-apoptotic proteins, drug sequestration and enhanced DND repair. This review delineates the distinct metabolic reprogramming patterns and the association between metabolism and anticancer drug resistance in DLBCL as well as the emerging strategies to surmount chemoresistance in DLBCL.
癌细胞代谢，包括有氧糖酵解、氨基酸和脂肪酸代谢，已得到广泛研究。代谢重编程是癌症的一个主要标志，它促进癌细胞增殖、进展和转移，同时引发对化疗药物的耐药性。几种信号转导途径，如BCR、MEK/ERK、Notch、NF-κB和PI3K/AKT/mTOR，调节肿瘤代谢，从而促进肿瘤细胞生长、增殖和进展。因此，靶向代谢酶、代谢产物或其信号转导途径可能构成一种有前景的治疗策略，以提高癌症治疗效果。弥漫性大B细胞淋巴瘤（DLBCL）是最具侵袭性的非霍奇金淋巴瘤（NHL）形式，三分之一的DLBCL患者在化疗后会出现复发/难治性疾病。耐药机制很复杂，包括靶基因突变、代谢重编程、异常信号转导途径、通过P-糖蛋白等多药外排转运蛋白的过表达增强药物外排、抗凋亡蛋白上调、药物隔离和DNA修复增强。本综述阐述了DLBCL中独特的代谢重编程模式以及代谢与抗癌药物耐药性之间的关联，以及克服DLBCL化疗耐药性的新兴策略。
