在泛癌环境中ALK融合:另一个瘤无关的目标?
Aditya Shreenivas1, Filip Janku2, Mohamed A Gouda3
1Medical College of Wisconsin (MCW) Cancer Center, Milwaukee, WI, USA. ashreenivas@mcw.edu.
NPJ precision oncology
|September 29, 2023
概括
形淋巴瘤激酶 (ALK) 抑制剂在各种癌症中具有显著的疗效,具有ALK融合/重组,显示出组织无关的活性. 这些向疗法提供了除非小细胞肺癌之外的有希望的治疗选择.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 遗传学 遗传学 是一个
背景情况:
- 无细胞淋巴瘤激酶 (ALK) 改变,包括融合/重组,突变和放大,涉及约3.3%的所有癌症.
- ALK融合/重组在炎症性肌纤维细胞瘤 (IMTs) 和形大细胞淋巴瘤 (ALCLs) 中尤为普遍,在这些亚型中超过50%.
- 虽然ALK变化在非小细胞肺癌 (NSCLC) 中很常见,但它们在其他癌症中发生的频率较低,通常低于0.2%.
研究的目的:
- 审查Anaplastic淋巴瘤激酶 (ALK) 改变的药理学可处理性,特别关注非小细胞肺癌 (NSCLC) 之外的癌症.
- 总结FDA批准的ALK抑制剂在各种瘤类型中的疗效和反应率.
- 突出ALK抑制剂在患有ALK融合/重组的瘤中的潜在组织无关活性.
主要方法:
- 对研究形淋巴瘤激酶 (ALK) 变化及其对ALK抑制剂的反应的文献综述.
- 对已批准的ALK抑制剂 (alectinib,brigatinib,ceritinib,crizotinib,lorlatinib) 疗效的临床试验数据和病例报告的分析.
- 专注于识别超出非小细胞肺癌 (NSCLC) 的反应率和瘤类型.
主要成果:
- 五种无细胞淋巴瘤激酶 (ALK) 抑制剂被FDA批准用于ALK异常非小细胞肺癌 (NSCLC),crizotinib也被批准用于ALK异常IMT和ALCL.
- 形淋巴瘤激酶 (ALK) 抑制剂在ALK融合/重组的癌症中显示出大约50-85%的显著反应率.
- 在广泛的固体和血液瘤中报告了ALK抑制剂的活性,这些瘤具有ALK融合/重新排列,以及ALK突变的神经母细胞瘤,尽管反应率较低.
结论:
- 形淋巴瘤激酶 (ALK) 抑制剂在治疗各种由ALK融合/重组为特征的癌症方面表现出显著的疗效.
- 这些数据强烈表明,无细胞淋巴瘤激酶 (ALK) 抑制剂在ALK融合/重组的瘤中具有组织不可知活性.
- 需要进一步的研究和临床试验,以探索ALK抑制剂在各种瘤环境中的全部潜力.
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