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Hendriks LE, Kerr KM, Menis J, Mok TS, Nestle U, Passaro A, Peters S, Planchard D, Smit EF, Solomon BJ, Veronesi G, Reck M; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Non-oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023 Apr;34(4):358-376. doi: 10.1016/j.annonc.2022.12.013. Epub 2023 Jan 17. PMID: 36669645.
Non-oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up - PubMed
非致癌基因成瘾
非致癌基因成瘾（Non-oncogene addiction）一词指的是恶性转化伴随着应激管理细胞途径（如蛋白毒性应激，氧化应激，代谢应激，DNA损伤应激等）的过渡激活，这些途径本身无法驱动肿瘤发生，但却是肿瘤进展所必需的。
目前在临床或后期临床开发中使用的几种抗癌药并不直接针对致癌变异，而是抑制随着肿瘤发生而出现的应激反应途径，如目前全球多个监管机构批准的多款PARP抑制剂用于治疗BRCA1/2突变（导致同源重组修复缺陷）乳腺癌、卵巢癌和前列腺癌。5,6 类似的还有：CDK4/6，VEGFA，TGFβ，ATM，BLC-2等。
▲ 非致癌基因成瘾细胞效应示意图：癌细胞会升高各种应激水平，这是由致瘤过程中的附带事件引起的；通过施加额外的压力或通过抑制特定的补救途径可特异性杀死肿瘤细胞，而正常细胞不受影响
Figure 1. Treatment algorithm for stage IV SqCC without contraindications for immunotherapy. Figure 2. Treatment algorithm for stage IV NSqNSCC after negative findings on molecular tests and without contraindication for immunotherapy. Figure 3. Treatment algorithm for stage IV SqCC with contraindication for immunotherapy. Figure 4. Treatment algorithm for stage IV NSqNSCC after negative findings on molecular tests and with contraindication for immunotherapy.
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