RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Strategies for the treatment of HER2(+) advanced breast cancer based on clinical practice in Chinese patients: a roundtable discussion.
Strategies for the treatment of HER2(+) advanced breast cancer based on clinical practice in Chinese patients: a roundtable discussion.
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人表皮生长因子受体 2 阳性(HER2+)乳腺癌早期易复发和转移,通常较雌激素受体阳性(ER+)、HER2 阴性乳腺癌临床行为更具侵袭性,患者生存结局更差。曲妥珠单抗及其他多种新型 HER2 靶向抗肿瘤药物已显著改善 HER2+ 乳腺癌治疗。曲妥珠单抗联合帕妥珠单抗已成为晚期 HER2+ 患者标准一线治疗;在中国患者中,吡咯替尼联合卡培他滨是优选二线方案。
然而,目前尚无推荐的三线及后线方案,这些患者仍有未满足治疗需求。Margetuximab 是一种人/鼠嵌合抗 HER2 IgG1 单克隆抗体(mAb),以曲妥珠单抗的鼠前体为基础。其自然杀伤(NK)细胞介导的抗体依赖性细胞介导细胞毒作用(ADCC)较曲妥珠单抗更强,可能成为 HER2+ 转移性乳腺癌患者在二线小分子酪氨酸激酶抑制剂(TKI)治疗进展后的优选方案。本文结合中国临床实践探讨抗 HER2 药物治疗策略,并总结抗 HER2 TKI 后治疗指南推荐中的共识和争议,为既往接受 TKI 治疗的 HER2+ 转移性乳腺癌患者三线及后线治疗提供参考。
Human epithelial growth factor receptor 2-positive (HER2 + ) breast cancer is easy to relapse and metastasize in the early stage, and usually has more aggressive clinical behavior and worse patient survival outcomes as compared with estrogen receptor-positive (ER + ), HER2-negative (HER2 - ) breast cancer.
The HER2 + breast cancer has been significantly enhanced by trastuzumab and other multiple novel HER2 anti-tumor drugs. The dual combination regimen of trastuzumab + pertuzumab has been established as the standard first-line therapy for advanced HER2 + patients, and pyrotinib with capecitabine is the preferred second-line treatment in Chinese patients.
However, no third- or later-line regimens are currently recommended, and thus, the treatment needs of these patients remain unmet. Margetuximab is a human/mouse chimeric anti-HER2 immunoglobulin G1 (IgG1) monoclonal antibody (mAb) based on the murine precursor of trastuzumab, has shown greater efficacy than trastuzumab in terms of its natural killer (NK) cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) effect and may become the preferred solution for HER2 + metastatic breast cancer (mBC) following progression on second-line therapy with small molecule tyrosine kinase inhibitors (TKIs).
This paper explores discussion of therapeutic strategies of anti-HER2 drugs based on Chinese clinical practice, and summarizes the consensus and controversy in the post-anti-HER2 TKIs guideline recommendations, so as to provide certain guidance to HER2 + mBC patients pretreated with TKIs in the third or later lines.
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