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Integration of Next-generation Sequencing and Immune Checkpoint Inhibitors in Targeted Symptom Control and Palliative Care in Solid Tumor Malignancies: A Multidisciplinary Clinician Perspective

机译:在实体瘤恶性肿瘤的靶向症状控制和姑息治疗中整合下一代测序和免疫检查点抑制剂:多学科临床医生的观点

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The molecular characterization of solid tumor malignancies with respect to tumorgenesis, risk stratification, and prognostication of chemotherapeutic side effects is multi-faceted. Characterizing these mechanisms requires a detailed understanding of cytogenetics and pharmacology. In addition to the standard palliative care interventions that address issues such as fatigue, neuropathy, performance status, depression, nutrition, cachexia, anxiety, and medical ethics, we must also delve into individual chemotherapy side effects. Comprehending these symptoms is more complex with the advent of broader targeted therapies. With the advent and initiation of Foundation Medicine (FMI) testing, we have been able to tailor regimens to the individual genetics of the patient. Next-generation sequencing (NGS) is a bioinformatic analysis used in order to create a targeted effort to understand the complex genetics of a vast array of malignancies. Through the process known as high-throughput sequencing we, as clinicians, can obtain more real-time genetic data and incorporate the information into our reasoning process. The process involves a broad manner in which deoxyribonucleic acid (DNA) sequence data is obtained including genome sequencing and resequencing, protein-DNA or proteinomics, chromatin immunoprecipitation (ChIP)-sequencing, ribonucleic acid (RNA) sequencing, and epigenomic analysis. High-throughput sequencing techniques including single molecule real-time sequencing, ion semiconductor sequencing, pyrose sequencing, sequencing by synthesis, sequencing by ligation, nanopore sequencing, and chain termination (otherwise known as Sanger sequencing) have expanded the realm of NGS and clinicians options.
机译:关于肿瘤发生,风险分层和化学治疗副作用预后的实体肿瘤恶性肿瘤的分子表征是多方面的。表征这些机制需要对细胞遗传学和药理学的详细了解。除了解决诸如疲劳,神经病,行为状态,抑郁,营养,恶病质,焦虑和医学道德等问题的标准姑息治疗干预措施外,我们还必须研究个别化学疗法的副作用。随着更广泛的靶向疗法的出现,对这些症状的理解更加复杂。随着基础医学(FMI)测试的出现和开始,我们已经能够根据患者的个体遗传学量身定制方案。下一代测序(NGS)是一种生物信息学分析,用于进行有针对性的研究,以了解各种恶性肿瘤的复杂遗传学。通过称为高通量测序的过程,我们作为临床医生,可以获得更多的实时遗传数据,并将信息纳入我们的推理过程。该过程涉及获取脱氧核糖核酸(DNA)序列数据的广泛方式,包括基因组测序和重测序,蛋白质DNA或蛋白质组学,染色质免疫沉淀(ChIP)测序,核糖核酸(RNA)测序和表观基因组分析。高通量测序技术,包括单分子实时测序,离子半导体测序,焦糖测序,合成测序,连接测序,纳米孔测序和链终止(也称为Sanger测序),扩展了NGS领域和临床医生的选择。

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