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中华乳腺病杂志(电子版) ›› 2022, Vol. 16 ›› Issue (02) : 67 -73. doi: 10.3877/cma.j.issn.1674-0807.2022.02.001

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肿瘤生态环境调控乳腺肿瘤耐药
宋尔卫1,()   
  1. 1. 510120 广州,中山大学孙逸仙纪念医院逸仙乳腺肿瘤医院
  • 收稿日期:2022-03-29 出版日期:2022-04-01
  • 通信作者: 宋尔卫

Ecological environment of tumor modulates drug resistance of breast tumor

Erwei Song1,()   

  1. 1. Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
  • Received:2022-03-29 Published:2022-04-01
  • Corresponding author: Erwei Song
引用本文:

宋尔卫. 肿瘤生态环境调控乳腺肿瘤耐药[J]. 中华乳腺病杂志(电子版), 2022, 16(02): 67-73.

Erwei Song. Ecological environment of tumor modulates drug resistance of breast tumor[J]. Chinese Journal of Breast Disease(Electronic Edition), 2022, 16(02): 67-73.

乳腺肿瘤的系统性治疗(化疗、内分泌治疗和靶向治疗等)是目前降低乳腺癌患者复发风险,延长其生存的主要手段。然而,仍有40%乳腺癌患者在治疗过程中或治疗结束后出现耐药,导致疾病进展,提示上述传统治疗方案未能彻底清除肿瘤细胞。肿瘤生态学说的提出从一个全新的角度为理解肿瘤治疗的耐受和药物新靶点的研发提供了新的契机。肿瘤生态学说认为肿瘤与周围及远处微环境等相互作用从而影响肿瘤的发生、发展及其对治疗的敏感性。在本文中,笔者剖析了由乳腺癌细胞群和微环境组成的肿瘤生态环境与乳腺癌耐药机制之间的关系,并结合相关临床研究进展加以阐述,以期为逆转乳腺癌耐药提供新的思路和治疗策略。

Systemic therapy including chemotherapy, endocrine therapy and targeted therapy, is currently performed to reduce the risk of recurrence and prolong the survival of breast cancer patients. However, almost 40% breast cancer patients suffer recurrence due to drug resistance, suggesting that traditional treatment regimens fail to completely kill tumor cells. The theory of tumor ecology provides a new insight to understand treatment resistance of tumors and find new targets of drugs. According to tumor ecology, the interaction between tumors and surrounding microenvironment can affect the initiation, development and treatment sensitivity of tumors. In this review, the author illustrates the relationship between drug resistance of breast cancer and tumor ecological environment composed of breast cancer cells and microenvironment, and reviews the related clinical research progress, in order to provide references for reversing drug resistance of breast cancer.

图1 肿瘤生态环境调控乳腺癌耐药的机制注:CD为白细胞分化抗原
表1 乳腺癌免疫治疗相关临床研究汇总
乳腺癌 临床试验 分期 研究目的 状态 重要结果 参考文献
三阴型 KEYNOTE-119(NCT02555657) 3期 PD-L1抑制剂帕博利珠单克隆抗体比卡培他滨、艾立布林、吉西他滨或长春瑞滨 完成 mOS:12.7个月比11.6个月,HR= 0.78 [26]
  IMpassion 030(NCT03498716) 3期 PD-L1抑制剂tezolizumab+蒽环类+紫杉醇比蒽环类+紫杉醇 进行中 NA [27]
  A-BRAVE(NCT02926196) 3期 PD-L1抑制剂avelumab比观察 进行中 NA [28]
  SWOG 1418(NCT02954874) 3期 PD-L1抑制剂帕博利珠单克隆抗体比观察 进行中 NA [29]
  SAFIR02- BREAST IMMUNO (NCT02299999) 2期 PD-L1抑制剂durvalumab比化疗 完成 mOS: 21.7个月比17.9个月,HR = 0.84 [30]
  DORA(NCT03167619) 2期 奥拉帕尼+ PD-L1抑制剂durvalumab比奥拉帕尼 进行中 NA [31]
  KEYLYNK-009(NCT04191135) 2期/3期 PD-L1抑制剂帕博利珠单克隆抗体+奥拉帕尼比PD-L1抑制剂帕博利珠单克隆抗体+化疗 进行中 NA [32]
  KEYNOTE-173(NCT02622074) 1b期 PD-L1抑制剂帕博利珠单克隆抗体+白蛋白紫杉醇+多柔比星+环磷酰胺比PD-L1抑制剂帕博利珠单克隆抗体+白蛋白紫杉醇+多柔比星+环磷酰胺+卡铂 完成 pCR率:60%;1年OS率:80%~100% [33]
激素受体阳性型 I-SPY2 NCT01042379 2期 PD-L1抑制剂帕博利珠单克隆抗体+紫杉醇+多柔比星+环磷酰胺比标准治疗(紫杉醇+多柔比星+环磷酰胺) 完成 pCR率:30%比13% [34]
  EYNOTE-28 NCT02054806 1b期 PD-L1抑制剂帕博利珠单克隆抗体 完成 mOS:8.6个月 [35]
  NCT03051659 2期 PD-L1抑制剂帕博利珠单克隆抗体+艾立布林比艾立布林 完成 mPFS:4.1个月比4.2个月 [36]
  NCT02971748 2期 PD-L1抑制剂帕博利珠单克隆抗体+内分泌治疗 进行中 NA [37]
  NCT03879174 2期 PD-L1抑制剂帕博利珠单克隆抗体+他莫昔芬 进行中 NA [38]
HER-2阳性型 KATE2(NCT02924883) 2期 T-DM1+PD-L1抑制剂阿特珠单克隆抗体比T-DM1 完成 pCR率:57.6%比41.4% [39]
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