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小细胞肺癌的临床用药方案现状及潜在靶点药物治疗方案新进展                                                                     Δ



                          2
                                          1, 3 #
                                  3
          章欢琪 ,林 旭 ,沈姝颖 ,李杨玲 (1.浙江大学药学院/临床药学研究中心,杭州 310006;2.浙江大学医学
                 1*
          院附属第一医院胸外科,杭州 310006;3.浙江大学医学院附属杭州市第一人民医院临床药理研究室/浙江省临
          床肿瘤药理与毒理学研究重点实验室,杭州 310006)

          中图分类号  R979.1;R734.2      文献标志码  A      文章编号  1001-0408(2023)16-2039-05
          DOI  10.6039/j.issn.1001-0408.2023.16.23


          摘  要  小细胞肺癌(SCLC)约占肺癌的15%,恶性程度高,异质性和侵袭性均较强。依托泊苷联合铂类是广泛期SCLC标准一
          线治疗的基础,但存在易耐药、易复发的问题。近年来,新型免疫药物和新型细胞毒性药物的出现在一定程度上提高了SCLC患
          者的生存率,为复发/难治型SCLC患者带来了治疗希望。本文通过综述SCLC临床用药方案的现状和潜在靶点药物治疗方案的
          新进展发现,目前SCLC一、二、三线方案包括依托泊苷+卡铂、阿替利珠单抗+依托泊苷+铂类药物、阿得贝利单抗、拓扑替康、多西他
          赛等,作用靶点主要集中在拓扑异构酶Ⅱ/Ⅰ、DNA、免疫检查点分子程序性死亡受体1/程序性死亡受体配体1、微管蛋白等;潜在靶点
          药物治疗方案包括阿立塞替+紫杉醇、洛伐妥珠单抗、APG-1252等,作用靶点主要集中在DNA损伤应答通路和免疫通路,可通过极光
          激酶A等多种潜在靶点来发挥抗肿瘤作用,实现延长患者生存期的治疗目标。
          关键词  小细胞肺癌;化疗;免疫治疗;作用靶点;潜在靶点药物治疗方案

          Status  quo  of  current  clinical  drug  regimens  for  small  cell  lung  cancer  and  new  progress  in  the  potential
          target drug therapeutic regimens
          ZHANG Huanqi ,LIN Xu ,SHEN Shuying ,LI Yangling (1.  College  of  Pharmaceutical  Sciences/Research
                                                 3
                                                              1, 3
                        1
                                  2
          Center for Clinical Pharmacy, Zhejiang University, Hangzhou 310006, China;2. Dept. of Thoracic Surgery, the
          First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China;3. Dept. of Clinical
          Pharmacology/Zhejiang  Key  Laboratory  of  Clinical  Cancer  Pharmacology  and  Toxicology  Research,  the
          Affiliated  Hangzhou  First  People’s  Hospital,  Zhejiang  University  School  of  Medicine,  Hangzhou  310006,
          China)

          ABSTRACT   Small cell lung cancer (SCLC) accounts for about 15% in lung cancer and is highly malignant, heterogeneous and
          invasive.  Etoposide  combined  with  platinum-based  chemotherapy  is  the  basis  of  standard  first-line  treatment  for  extensive-stage
          SCLC,  but  suffers  from  the  problem  of  susceptibility  to  drug  resistance  and  relapse.  In  recent  years,  the  emergence  of  new
          immunological drugs and novel cytotoxic drugs has improved the survival of SCLC patients to a certain extent, especially bringing
          therapeutic hope to patients with relapsed/refractory SCLC. In this paper, we review the current clinical drug regimens and the new
          progress  of  potential  target  drug  therapeutic  regimens  for  the  treatment  of  SCLC.  At  present,  the  first- ,  second-  and  third-line
          schemes  of  SCLC  include  etoposide+carboplatin,  atezolizumab+etoposide+platinum,  adebrelimab,  topotecan,  docetaxel,  etc.;  the
          current  drug  targets  for  the  treatment  of  SCLC  mainly  focus  on  topoisomerase  Ⅱ/Ⅰ,  DNA,  the  immune  checkpoint  molecules
          programmed  death-1/programmed  death-ligand  1,  tubulin,  etc.  The  potential  target  drug  therapeutic  options  include  alisertib+
          paclitaxel, rovalpituzumab, APG-1252, etc., and mainly focus on DNA damage response pathways and immune pathways, which
          can achieve the prolongation of patient survival by exerting anti-tumor effects through aurora kinase A and other potential targets.
          KEYWORDS    small cell lung cancer; chemotherapy; immunotherapy; therapeutic targets; potential target drug therapeutic options



              肺癌是全球发病率和病死率均排名首位的恶性肿                         (small cell lung cancer,SCLC)和非小细胞肺癌(non-
            [1]
          瘤 。依照组织病理学特征可将肺癌分为小细胞肺癌                            small cell lung cancer,NSCLC),其中 SCLC 约占肺癌的
                                                                 [2]
             Δ 基金项目 浙江省临床肿瘤药理与毒理学研究重点实验室(No.                 15% 。SCLC 恶性程度高,异质性和侵袭性均较强,且
          2020E10021)                                        容易发生淋巴结转移。多数SCLC患者确诊时已处于广
             *第一作者 硕士研究生。研究方向:临床药学。电话:0571-
                                                             泛期,且常伴有内分泌异常,病情发展迅速,转移部位以
          56007823。E-mail:3180102525@zju.edu.cn
                                                             脑、肝、肾上腺、骨和骨髓较为常见 。SCLC治疗药物主
                                                                                          [3]
             # 通信作者 副主任药师,博士。研究方向:肿瘤药理。电话:
          0571-56007823。E-mail:yanglingli@zju.edu.cn         要包括以铂类药物为代表的化疗药和以靶向程序性死

          中国药房  2023年第34卷第16期                                              China Pharmacy  2023 Vol. 34  No. 16    · 2039 ·
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