[關(guān)鍵詞]
[摘要]
近年來(lái)全球血液腫瘤的發(fā)生率呈現(xiàn)不斷上升趨勢(shì),2022年全球非霍奇金淋巴瘤和白血病的發(fā)病及死亡順位均為第10位,全球的癌癥負(fù)擔(dān)也進(jìn)一步加重。雖然近年來(lái)全球監(jiān)管部門批準(zhǔn)的抗癌新藥數(shù)量呈逐年上升趨勢(shì),但實(shí)際上只有極少數(shù)通過(guò)監(jiān)管部門審批,根本原因是絕大多數(shù)在臨床前具有良好藥效的抗癌新藥在臨床治療中未能表現(xiàn)出良好的治療作用,并且缺乏臨床前抗腫瘤藥物藥效學(xué)評(píng)價(jià)的可靠模型。人源腫瘤異種移植(PDX)模型是將患者的腫瘤組織、原代腫瘤細(xì)胞經(jīng)原位或異位植入到免疫缺陷鼠體內(nèi)所形成的移植瘤模型。與傳統(tǒng)的細(xì)胞檢測(cè)及同系腫瘤小鼠模型相比,血液腫瘤小鼠PDX模型具有可保持患者腫瘤的異質(zhì)性和遺傳多樣性,準(zhǔn)確反映疾病進(jìn)展和藥物的療效等優(yōu)勢(shì)。目前已經(jīng)建成多種血液腫瘤小鼠PDX模型,如T細(xì)胞或B細(xì)胞急性淋巴細(xì)胞白血?。ˋLL)、間變性大細(xì)胞淋巴瘤(ALCL)、彌漫性大B細(xì)胞淋巴瘤(DLBCL)、皮膚T細(xì)胞淋巴瘤(CTCL)、髓系白血?。∕L)、外周T細(xì)胞淋巴瘤(PTCL)等。上述血液腫瘤PDX模型的建立為血液腫瘤發(fā)生機(jī)制研究、抗癌新藥的篩選及藥效學(xué)評(píng)價(jià)、個(gè)體化精準(zhǔn)醫(yī)療等提供了可靠的試驗(yàn)數(shù)據(jù)。從血液腫瘤PDX模型構(gòu)建的考慮因素、模型構(gòu)建成功的條件及驗(yàn)證方法,應(yīng)用現(xiàn)狀,以及所面臨的挑戰(zhàn)和未來(lái)發(fā)展前景方面進(jìn)行綜述,以期為我國(guó)相關(guān)抗腫瘤藥物的藥效評(píng)價(jià)模型的構(gòu)建及應(yīng)用提供借鑒。
[Key word]
[Abstract]
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.
[中圖分類號(hào)]
R965.2
[基金項(xiàng)目]
中國(guó)食品藥品檢定研究院關(guān)鍵技術(shù)研究基金(GJJS-2022-6-5)