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The advent of precision medicine has changed the landscape of oncologic biomarkers, drug discovery, drug development, and, more importantly, outcomes for patients with cancer. Precision oncology entails the genomic profiling of tumors to detect actionable aberrations. The advances in clinical next-generation sequencing from both tumor tissue and liquid biopsy and availability of targeted therapies has rapidly entered mainstream clinical practice. In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered “undruggable” for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated. 相似文献
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Takeshi Nagashima Ken Yamaguchi Kenichi Urakami Yuji Shimoda Sumiko Ohnami Keiichi Ohshima Tomoe Tanabe Akane Naruoka Fukumi Kamada Masakuni Serizawa Keiichi Hatakeyama Kenya Matsumura Shumpei Ohnami Koji Maruyama Tohru Mochizuki Masatoshi Kusuhara Akio Shiomi Yasuhisa Ohde Masanori Terashima Katsuhiko Uesaka Tetsuro Onitsuka Seiichiro Nishimura Yasuyuki Hirashima Nakamasa Hayashi Yoshio Kiyohara Yasuhiro Tsubosa Hirohisa Katagiri Masashi Niwakawa Kaoru Takahashi Hiroya Kashiwagi Masahiro Nakagawa Yuji Ishida Takashi Sugino Mitsuru Takahashi Yasuto Akiyama 《Cancer science》2020,111(2):687-699
This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single‐center study called “High‐tech Omics‐based Patient Evaluation” or “Project HOPE” conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole‐exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed “Shizuoka Multi‐omics Analysis Protocol” developed in‐house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non–cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients. 相似文献
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Li Zhang Ming-Jie Wang Wei Wang Jing-Ya Zhao Jia-Liang Wu Yan-Pu Liu Hong Zhu Jie-Ming Qu Min Zhou 《International journal of cancer. Journal international du cancer》2020,146(1):103-114
Next-generation sequencing of cell-free circulating DNA (cfDNA) has emerged as promising technique for identifying minimally invasive genomic profiling of tumor cells recently. However, it remains relatively unknown in LAM disease. In our study, paired cfDNA and genomic DNA (gDNA) in blood samples were obtained from 23 LAM patients and seven healthy controls to explore mutations profiles of targeted 70 cancer-related genes. As results, log2-based allele frequencies of mutations in cfDNA were significantly different from those of gDNA. By comparing the mutual mutations identified both in cfDNA and gDNA, a significant correlation was also observed. After removing mutations in gDNA, distinct somatic mutation profiles of cfDNA were observed in LAM patients. Forty of 70 targeted genes had recurrent mutations, of which ATM, BRCA2 and APC showed the highest frequency. Based on the mutation, correlation network constructed of 40 mutated genes, 11 hub genes bearing intensive interactions were highlighted, including BRCA1, BRCA2, RAD50, RB1, NF1, APC, MLH3, ATM, PDGFRA, PALB2 and BLM. Expression of the hub genes showed significant clusters between LAM patients and controls and that RAD50 and BRCA2 had the strongest associations with subject phenotypes. Myogenesis and estrogen response were confirmed to be positively regulated in LAM patients. Collectively, our study provided a landscape of genomic alterations in LAM and discovered several potential driver genes, that is, BRCA2 and RAD50, which shed a substantial light on the clinical application of key molecular markers and potential therapy targets for precision diagnosis and treatment in the future. 相似文献
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Alessandra Iurlo Elena Maria Elli Francesca Palandri Daniele Cattaneo Anna Bossi Ivan Cortinovis Cristina Bucelli Nicola Orofino Filippo Brioschi Giuseppe Auteri Paola Bianchi Sonia Fabris Giuseppe Isimbaldi Elena Sabattini Luca Baldini Umberto Gianelli 《Hematological oncology》2019,37(4):424-433
Currently available prognostic scoring systems in primary myelofibrosis (PMF) do not integrate clinical, histological, and molecular data, or they also required information on “other” mutations that are available in the clinical practice only in a very limited number of laboratories. In the present multicenter study, including 401 PMF patients, an integrated International Prognostic Scoring System (I‐IPSS) was developed by combining IPSS, grade of bone marrow fibrosis (GBMF), and driver mutations molecular status (MS) to define PMF prognosis at diagnosis. Four prognostic categories were identified: I‐IPSS–low risk (113 patients), I‐IPSS–intermediate‐1 risk (56 patients), I‐IPSS–intermediate‐2 risk (154 patients), and I‐IPSS–high risk (78 patients). Median overall survival was 26.7 years in I‐IPSS–intermediate‐1, 10.8 in I‐IPSS–intermediate‐2, and 6.4 in I‐IPSS‐high‐risk patients (log‐rank test <0.0001); instead, it was not reached in the I‐IPSS–low‐risk cohort because of the extremely low number of registered deaths. The addition of GBMF and MS to IPSS improved the efficacy for predicting the risk of death. Indeed, the sensitivity of I‐IPSS was significantly higher (P < .05) than that of IPSS, considering both total deaths and 5‐ and 10‐year mortality. This comprehensive approach allows clinicians to evaluate mutual interactions between IPSS, GBMF, and MS and identify high‐risk patients with poor prognosis who may benefit from aggressive treatments. More importantly, this integrated score can be easily applicable worldwide as it only required information that represent the good clinical practice in the management of PMF patients. 相似文献
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Ashton A. Connor Robert E. Denroche Gun Ho Jang Mathieu Lemire Amy Zhang Michelle Chan-Seng-Yue Gavin Wilson Robert C. Grant Daniele Merico Ilinca Lungu John M.S. Bartlett Dianne Chadwick Sheng-Ben Liang Jenna Eagles Faridah Mbabaali Jessica K. Miller Paul Krzyzanowski Heather Armstrong Steven Gallinger 《Cancer cell》2019,35(2):267-282.e7
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Caitlin A. McIntyre MD Sharon A. Lawrence MD Allison L. Richards PhD Joanne F. Chou MPH Winston Wong MD Marinela Capanu PhD Michael F. Berger PhD Mark T. A. Donoghue PhD Kenneth H. Yu MD Anna M. Varghese MD David P. Kelsen MD Wungki Park MD Vinod P. Balachandran MD T. Peter Kingham MD Michael I. D’Angelica MD Jeffrey A. Drebin MD PhD William R. Jarnagin MD Christine A. Iacobuzio-Donahue MD PhD Peter J. Allen MD Eileen M. O’Reilly MD 《Cancer》2020,126(17):3939-3949
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综合康复治疗出租车驾驶员腰间盘突出症的临床研究 总被引:1,自引:0,他引:1
目的观察综合康复治疗出租车驾驶员腰间盘突出症的临床疗效。方法应用药物、牵引、特定肌深层按摩疗法以及易化牵伸术等综合治疗出租车驾驶员腰间盘突出症,与常规牵引按摩作对照。结果经过2个疗程治疗,综合康复治疗出租车驾驶员腰间盘突出症明显优于常规牵引按摩组,组间比较有统计学意义(P〈0.05)。结论髂腰肌、胭绳肌以及胫骨前肌损伤可能为增剧出租车驾驶员腰间盘突出症的因素之一,针对其综合康复效果显著。 相似文献