近年来全球血液肿瘤的发生率呈现不断上升趋势，2022年全球非霍奇金淋巴瘤和白血病的发病及死亡顺位均为第10位，全球的癌症负担也进一步加重。虽然近年来全球监管部门批准的抗癌新药数量呈逐年上升趋势，但实际上只有极少数通过监管部门审批，根本原因是绝大多数在临床前具有良好药效的抗癌新药在临床治疗中未能表现出良好的治疗作用，并且缺乏临床前抗肿瘤药物药效学评价的可靠模型。人源肿瘤异种移植（PDX）模型是将患者的肿瘤组织、原代肿瘤细胞经原位或异位植入到免疫缺陷鼠体内所形成的移植瘤模型。与传统的细胞检测及同系肿瘤小鼠模型相比，血液肿瘤小鼠PDX模型具有可保持患者肿瘤的异质性和遗传多样性，准确反映疾病进展和药物的疗效等优势。目前已经建成多种血液肿瘤小鼠PDX模型，如T细胞或B细胞急性淋巴细胞白血病（ALL）、间变性大细胞淋巴瘤（ALCL）、弥漫性大B细胞淋巴瘤（DLBCL）、皮肤T细胞淋巴瘤（CTCL）、髓系白血病（ML）、外周T细胞淋巴瘤（PTCL）等。上述血液肿瘤PDX模型的建立为血液肿瘤发生机制研究、抗癌新药的筛选及药效学评价、个体化精准医疗等提供了可靠的试验数据。从血液肿瘤PDX模型构建的考虑因素、模型构建成功的条件及验证方法，应用现状，以及所面临的挑战和未来发展前景方面进行综述，以期为我国相关抗肿瘤药物的药效评价模型的构建及应用提供借鉴。

In recent years, the global incidence of hematological tumors has been showing a rising tendency, and in 2022, the global incidence and mortality of the non-Hodgkin lymphoma (NHL) and leukemia were ranked 10th, further increasing the global burden of cancer treatment. Although the number of anti-cancer new drugs approved by the regulatory authorities in the worldwide has been increasing in recent years, only very few of them have passed the regulatory approval. One of the important reasons was that the vast majority of new anti-cancer drugs with good preclinical efficacy have failed to show good therapeutic effects in clinical treatment, and there was a lack of reliable models for the efficacy of anti-cancer drugs in preclinical assessment. The patient-derived tumor xenograft (PDX) model is a transplant tumor model formed by implanting tumor tissue and primary tumor cells from patients orthodoxly or ectopically into immunodeficient animal. the immunodeficient mouse PDX model of the hematological tumors provides several key advantages over traditional cellular assays and syngeneic mouse blood tumor models, including preservation of a patient’s tumor heterogeneity and genetic diversity and a more accurate representation of disease progression and response to therapy. At present, various hematological tumor PDX models have been established, such as acute lymphoblastic leukemia (ALL), anaplastic large cell lymphoma (ALCL), diffuse large B cell lymphoma (DLBCL), cutaneous T-cell lymphoma (CTCL), myeloid leukemia (ML), peripheral T-cell lymphoma (PTCL), etc. The establishment of the above-mentioned tumor PDX model provides reliable experimental data for the study on the mechanism of the hematological tumors, screening and efficacy evaluation of anti-tumor drugs, and personalized precision medicine, etc. In this paper, the considerations for the construction of the hematological tumor PDX model, the successful conditions and verification methods of the model construction, the application status, and the challenges faced and the future development prospects were reviewed, in order to provide references for the construction and application of the efficacy assessment model of related anti-tumor drugs in China.

R965.2

中国食品药品检定研究院关键技术研究基金（GJJS-2022-6-5）