SCI
2 October
Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy
Skoulidis Ferdinandos,Heymach John V,Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy.[J] .Nat. Rev. Cancer, , 19: 495-509.
The impressive clinical activity of small-molecule receptor tyrosine kinase inhibitors for oncogene-addicted subgroups of non-small-cell lung cancer (for example, those driven by activating mutations in the gene encoding epidermal growth factor receptor (EGFR) or rearrangements in the genes encoding the receptor tyrosine kinases anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1) and rearranged during transfection (RET)) has established an oncogene-centric molecular classification paradigm in this disease.
小分子受体酪氨酸激酶抑制剂对非小细胞肺癌致癌基因亚组的令人印象深刻的临床活性已建立了一种以癌基因为中心的分子分类范例。（例如，由激活表皮生长因子受体（EGFR）基因突变或基因重排驱动的亚组）编码受体酪氨酸激酶，间变性淋巴瘤激酶（ALK），ROS原癌基因1（ROS1）并在转染过程中重新排列（RET））
However, recent studies have revealed considerable phenotypic diversity downstream of tumor-initiating oncogenes.Co-occurring genomic alterations, particularly in tumor suppressor genes such as TP53 and LKB1 (also known as STK11), have emerged as core determinants of the molecular and clinical heterogeneity of oncogene-driven lung cancer subgroups through their effects on both tumor cell-intrinsic and non-cell-autonomous cancer hallmarks.
但是，最近的研究表明，在肿瘤引发的癌基因下游存在大量的表型多样性。共同出现的基因组改变，特别是在肿瘤抑制基因如TP53和LKB1（也称为STK11）中，已通过癌基因驱动的肺癌亚群对肿瘤细胞内源性的影响而成为分子和临床异质性的核心决定因素和非细胞自主性癌症的标志。
In this Review, we discuss the impact of co-mutations on the pathogenesis, biology, microenvironmental interactions and therapeutic vulnerabilities of non-small-cell lung cancer and assess the challenges and opportunities that co-mutations present for personalized anticancer therapy, as well as the expanding field of precision immunotherapy.
在这篇综述中，我们讨论了共突变对非小细胞肺癌的发病机制，生物学，微环境相互作用和治疗脆弱性的影响，并评估了共突变对个性化抗癌治疗以及新的挑战和机遇，以及精准免疫治疗领域不断发展。
