Kim Dong-Wook, Kim Keun-Cheol, Kim Kee-Beom, Dunn Colin T, Park Kwon-Sik
Department of Microbiology, Immunology, and Cancer Biology, The University of Virginia Cancer Center, University of Virginia, Charlottesville, VA, USA.
Department of Biological Sciences, Kangwon National University, Chuncheon, Korea.
Transl Lung Cancer Res. 2018 Feb;7(1):4-20. doi: 10.21037/tlcr.2017.10.07.
The discovery of recurrent alterations in genes encoding transcription regulators and chromatin modifiers is one of the most important recent developments in the study of the small cell lung cancer (SCLC) genome. With advances in models and analytical methods, the field of SCLC biology has seen remarkable progress in understanding the deregulated transcription networks linked to the tumor development and malignant progression. This review will discuss recent discoveries on the roles of RB and P53 family of tumor suppressors and MYC family of oncogenes in tumor initiation and development. It will also describe the roles of lineage-specific factors in neuroendocrine (NE) cell differentiation and homeostasis and the roles of epigenetic alterations driven by changes in NFIB and chromatin modifiers in malignant progression and chemoresistance. These recent findings have led to a model of transcriptional network in which multiple pathways converge on regulatory regions of crucial genes linked to tumor development. Validation of this model and characterization of target genes will provide critical insights into the biology of SCLC and novel strategies for tumor intervention.
编码转录调节因子和染色质修饰因子的基因中反复出现的改变的发现，是小细胞肺癌（SCLC）基因组研究中最重要的最新进展之一。随着模型和分析方法的进步，SCLC生物学领域在理解与肿瘤发生和恶性进展相关的失调转录网络方面取得了显著进展。本综述将讨论肿瘤抑制因子RB和P53家族以及癌基因MYC家族在肿瘤起始和发展中的作用的最新发现。它还将描述谱系特异性因子在神经内分泌（NE）细胞分化和稳态中的作用，以及由NFIB和染色质修饰因子变化驱动的表观遗传改变在恶性进展和化疗耐药中的作用。这些最新发现导致了一种转录网络模型，其中多条途径汇聚于与肿瘤发展相关的关键基因的调控区域。该模型的验证和靶基因的表征将为SCLC生物学提供关键见解，并为肿瘤干预提供新策略。
