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用于治疗肺癌的靶向和细胞毒性抑制剂。

Targeted and cytotoxic inhibitors used in the treatment of lung cancers.

机构信息

Blue Ridge Institute for Medical Research, 221 Haywood Knolls Drive, Hendersonville, NC 28791, United States.

出版信息

Pharmacol Res. 2024 Nov;209:107465. doi: 10.1016/j.phrs.2024.107465. Epub 2024 Oct 18.

DOI:10.1016/j.phrs.2024.107465
PMID:39426470
Abstract

Lung cancer is the leading cause of cancer deaths in the United States and the world. It is divided into two major types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In the tumor-node-metastasis (TNM) cancer-staging classification system (Stages I/II/III/IV), the severity of neoplastic growth is characterized by the size of the tumor (T1 to T4), the extent of lymph node involvement (N0 to N3), and whether (M1) or not (M0) distant metastasis has occurred. Surgery is the treatment of choice for medically fit patients with Stage I/II NSCLC. Combination chemoradiotherapy and immune checkpoint inhibitor therapy are used across all NSCLC types. Oncogene-addicted tumors with sensitizing EGFR or BRAF mutations or activating ALK, ROS1 or NTRK translocations are treated with their cognate orally active small molecule protein kinase blockers. On the order of 20 % of NSCLCs bear activating mutations in EGFR and are treated with osimertinib and other kinase antagonists. SCLC, which accounts for approximately 15 % of lung cancer cases, is a deadly high-grade neuroendocrine carcinoma with a poor prognosis. Limited-stage SCLC is confined to one hemi-thorax and one radiation port and extensive-stage disease signifies those cancers that do not meet the criteria for limited-stage disease. Local treatment options to control thoracic disease include radiotherapy and surgery. In patients with extensive-stage disease, a platinum agent (cisplatin or carboplatin) combined with etoposide and an anti-PDL1 inhibitor (atezolizumab or durvalumab) for four cycles followed by anti-PDL1 maintenance therapy is the recommended first-line regimen.

摘要

肺癌是美国和全球癌症死亡的主要原因。它分为两种主要类型:小细胞肺癌(SCLC)和非小细胞肺癌(NSCLC)。在肿瘤-淋巴结-转移(TNM)癌症分期系统(I/II/III/IV 期)中,肿瘤生长的严重程度通过肿瘤的大小(T1 至 T4)、淋巴结受累的程度(N0 至 N3)以及是否(M1)或未发生(M0)远处转移来特征化。对于适合手术的 I/II 期 NSCLC 患者,手术是治疗的首选。联合化疗和免疫检查点抑制剂治疗用于所有 NSCLC 类型。对具有敏感 EGFR 或 BRAF 突变或激活 ALK、ROS1 或 NTRK 易位的癌基因成瘾肿瘤,用其同源的口服小分子蛋白激酶阻滞剂进行治疗。大约 20%的 NSCLC 具有激活的 EGFR 突变,用奥希替尼和其他激酶拮抗剂进行治疗。占肺癌病例约 15%的 SCLC 是一种致命的高级神经内分泌癌,预后不良。局限期 SCLC 局限于一个半胸廓和一个放射野,广泛期疾病表示那些不符合局限期疾病标准的癌症。控制胸部疾病的局部治疗选择包括放射治疗和手术。对于广泛期疾病患者,推荐的一线方案是含铂药物(顺铂或卡铂)联合依托泊苷和抗 PD-L1 抑制剂(阿替利珠单抗或度伐利尤单抗)四个周期,然后进行抗 PD-L1 维持治疗。

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