{"title":"基因组和基因表达研究有助于确定小细胞肺癌癌症和其他肺部神经内分泌肿瘤的异质性,并确定新的治疗靶点","authors":"U. Testa, E. Pelosi, G. Castelli","doi":"10.3390/onco2030013","DOIUrl":null,"url":null,"abstract":"Small-cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma, corresponding to about 15% of lung cancers, occurring predominantly in smokers and associated with a very poor prognosis. Key genetic alterations very frequently observed in SCLC are represented by the loss of TP53 and RB1, due to mutational events or deletions; frequent amplification or overexpression of MYC family genes (MYC, MYCL and MYCN); frequent genetic alterations by mutation/deletion of KMT2D, RB family members p107 (RBL1) and p130 (RBL2), PTEN, NOTCH receptors and CREBBP. The profile of expression of specific transcription factors allowed to differentiate four subtypes of SCLC defined according to levels of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POUF23 (SCLC-P) or YAP1 (SCLC-Y). A recent study identified the subgroup SCLC-I, characterized by the expression of inflammatory/immune-related genes. Recent studies have characterized at molecular level other lung neuroendocrine tumors, including large cell neuroendocrine cancers (LCNECs) and lung carcinoids. These molecular studies have identified some therapeutic vulnerabilities that can be targeted using specific drugs and some promising biomarkers that can predict the response to this treatment. Furthermore, the introduction of immunotherapy (immune checkpoint blockade) into standard first-line treatment has led to a significant clinical benefit in a limited subset of patients.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2022-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genomic and Gene Expression Studies Helped to Define the Heterogeneity of Small-Cell Lung Cancer and Other Lung Neuroendocrine Tumors and to Identify New Therapeutic Targets\",\"authors\":\"U. Testa, E. Pelosi, G. Castelli\",\"doi\":\"10.3390/onco2030013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Small-cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma, corresponding to about 15% of lung cancers, occurring predominantly in smokers and associated with a very poor prognosis. Key genetic alterations very frequently observed in SCLC are represented by the loss of TP53 and RB1, due to mutational events or deletions; frequent amplification or overexpression of MYC family genes (MYC, MYCL and MYCN); frequent genetic alterations by mutation/deletion of KMT2D, RB family members p107 (RBL1) and p130 (RBL2), PTEN, NOTCH receptors and CREBBP. The profile of expression of specific transcription factors allowed to differentiate four subtypes of SCLC defined according to levels of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POUF23 (SCLC-P) or YAP1 (SCLC-Y). A recent study identified the subgroup SCLC-I, characterized by the expression of inflammatory/immune-related genes. Recent studies have characterized at molecular level other lung neuroendocrine tumors, including large cell neuroendocrine cancers (LCNECs) and lung carcinoids. These molecular studies have identified some therapeutic vulnerabilities that can be targeted using specific drugs and some promising biomarkers that can predict the response to this treatment. Furthermore, the introduction of immunotherapy (immune checkpoint blockade) into standard first-line treatment has led to a significant clinical benefit in a limited subset of patients.\",\"PeriodicalId\":74339,\"journal\":{\"name\":\"Onco\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-08-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Onco\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/onco2030013\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Onco","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/onco2030013","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Genomic and Gene Expression Studies Helped to Define the Heterogeneity of Small-Cell Lung Cancer and Other Lung Neuroendocrine Tumors and to Identify New Therapeutic Targets
Small-cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma, corresponding to about 15% of lung cancers, occurring predominantly in smokers and associated with a very poor prognosis. Key genetic alterations very frequently observed in SCLC are represented by the loss of TP53 and RB1, due to mutational events or deletions; frequent amplification or overexpression of MYC family genes (MYC, MYCL and MYCN); frequent genetic alterations by mutation/deletion of KMT2D, RB family members p107 (RBL1) and p130 (RBL2), PTEN, NOTCH receptors and CREBBP. The profile of expression of specific transcription factors allowed to differentiate four subtypes of SCLC defined according to levels of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POUF23 (SCLC-P) or YAP1 (SCLC-Y). A recent study identified the subgroup SCLC-I, characterized by the expression of inflammatory/immune-related genes. Recent studies have characterized at molecular level other lung neuroendocrine tumors, including large cell neuroendocrine cancers (LCNECs) and lung carcinoids. These molecular studies have identified some therapeutic vulnerabilities that can be targeted using specific drugs and some promising biomarkers that can predict the response to this treatment. Furthermore, the introduction of immunotherapy (immune checkpoint blockade) into standard first-line treatment has led to a significant clinical benefit in a limited subset of patients.