肺癌罕见分子亚型

2023-03-16 10:23

与此同时，针对罕见分子亚型肺癌患者批准的靶向治疗的数量急剧增加。

SCI 15 March 2023

Rare molecular subtypes of lung cancer

(Nature reviews. Clinical oncology, IF: 65.011)

Harada G, Yang SR, Cocco E, Drilon A. Rare molecular subtypes of lung cancer. Nat Rev Clin Oncol. 2023 Feb 20. doi: 10.1038/s41571-023-00733-6. Epub ahead of print. PMID: 36806787.

Corresponding author:

Emiliano Cocco

Department of Biochemistry and Molecular

Biology/Sylvester Comprehensive Cancer Center, University of Miami/Miller School of Medicine, Miami, FL, USA.

Alexander Drilon

Department of Medicine, Weill Cornell Medical College, New York, NY , USA.

Abstract

Oncogenes that occur in ≤5% of non-small-cell lung cancers have been defined as 'rare'; nonetheless, this frequency can correspond to a substantial number of patients diagnosed annually. Within rare oncogenes, less commonly identified alterations (such as HRAS, NRAS, RIT1, ARAF, RAF1 and MAP2K1 mutations, or ERBB family, LTK and RASGRF1 fusions) can share certain structural or oncogenic features with more commonly recognized alterations (such as KRAS, BRAF, MET and ERBB family mutations, or ALK, RET and ROS1 fusions). Over the past 5 years, a surge in the identification of rare-oncogene-driven lung cancers has challenged the boundaries of traditional clinical grade diagnostic assays and profiling algorithms. In tandem, the number of approved targeted therapies for patients with rare molecular subtypes of lung cancer has risen dramatically. Rational drug design has iteratively improved the quality of small-molecule therapeutic agents and introduced a wave of antibody-based therapeutics, expanding the list of actionable de novo and resistance alterations in lung cancer. Getting additional molecularly tailored therapeutics approved for rare-oncogene-driven lung cancers in a larger range of countries will require ongoing stakeholder cooperation. Patient advocates, health-care agencies, investigators and companies with an interest in diagnostics, therapeutics and real-world evidence have already taken steps to surmount the challenges associated with research into low-frequency drivers.

在≤5%的非小细胞肺癌出现的致癌基因被定义为“罕见”；尽管如此，这一频率仍与每年确诊的大量患者相一致。在罕见致癌基因中，不太常见的突变（如HRAS、NRAS、RIT1、ARAF、RAF1和MAP2K1突变，或ERBB家族、LTK和RASGRF1融合）可以与更常见的突变（如KRAS、BRAF、MET和ERBB家族突变，或ALK、RET和ROS1融合）共享某些结构或致癌特征。在过去的5年里，罕见致癌基因驱动肺癌发现的激增，挑战了传统临床分级诊断分析和剖析算法的界限。

与此同时，针对罕见分子亚型肺癌患者批准的靶向治疗的数量急剧增加。合理的药物设计已经迭代地提高了小分子治疗药物的质量，并引入了一波基于抗体的治疗方法，扩大了肺癌可操作的全新和耐药替代治疗的列表。要在更大范围的国家批准更多针对罕见致癌基因驱动的肺癌的分子定制疗法，将需要利益相关者的持续合作。患者的拥护者、医疗保健机构、研究人员和对诊断、治疗和现实证据感兴趣的公司已经采取措施，克服低频驱动基因研究带来的挑战。