髓母细胞淋巴瘤（MCL）是一种致命的血液系统恶性肿瘤，中位生存期为4年。其致命性主要归因于对临床肿瘤进展和对当前治疗方案的抗药性的认识有限。自身内在的长期药物治疗和肿瘤微环境（TME）有助于为MCL细胞赋予促肿瘤和抗药性特性。因此，利用全球"统一"分析探究MCL进展中涉及新型药物靶点，从而改善疾病预防，是一个迫切的需求。通过整合转录组学分析MCL患者的数据，我们确定了成纤维细胞生长因子受体-1（FGFR1）的存在，并分析MCL患者样本显示高FGFR1表达与MCL患者整体生存期较短有关。通过药物干预和功能缺失研究，我们确定了一个新的MYC-EZH2-CDKN1C轴驱动的MCL细胞增殖过程。此外，药物的靶向作用，如选择性小分子靶向FGFR的厄达替尼，能够在体外诱导细胞周期阻滞和细胞死亡，在体内抑制肿瘤进展，并改善整体生存。我们在多个体内模型系统中进行了广泛的临床前评估，确认了厄达替尼在MCL中的治疗潜力，并将FGFR1确定为MCL中一个可行的治疗靶点。© 2023. 作者。

Mantle cell lymphoma (MCL) is a lethal hematological malignancy with a median survival of 4 years. Its lethality is mainly attributed to a limited understanding of clinical tumor progression and resistance to current therapeutic regimes. Intrinsic, prolonged drug treatment and tumor-microenvironment (TME) facilitated factors impart pro-tumorigenic and drug-insensitivity properties to MCL cells. Hence, elucidating neoteric pharmacotherapeutic molecular targets involved in MCL progression utilizing a global "unified" analysis for improved disease prevention is an earnest need. Using integrated transcriptomic analyses in MCL patients, we identified a Fibroblast Growth Factor Receptor-1 (FGFR1), and analyses of MCL patient samples showed that high FGFR1 expression was associated with shorter overall survival in MCL patient cohorts. Functional studies using pharmacological intervention and loss of function identify a novel MYC-EZH2-CDKN1C axis-driven proliferation in MCL. Further, pharmacological targeting with erdafitinib, a selective small molecule targeting FGFRs, induced cell-cycle arrest and cell death in-vitro, inhibited tumor progression, and improved overall survival in-vivo. We performed extensive pre-clinical assessments in multiple in-vivo model systems to confirm the therapeutic potential of erdafitinib in MCL and demonstrated FGFR1 as a viable therapeutic target in MCL.© 2023. The Author(s).