临床肿瘤基因组学与肿瘤个体化治疗

肿瘤治疗在循证医学的基础上逐渐向循因医学过渡,肿瘤个体化治疗已成为肿瘤治疗的发展方向。肿瘤患者对各种化疗药物存在明显的个体差异,其主要原因是患者个体肿瘤相关基因表达的差异和多态性。因此,逐步实现以肿瘤基因组学为指导的个体化治疗显得越来越重要。     

药物遗传学在肿瘤化疗中的应用

多数恶性肿瘤早期缺乏症状，就诊时已属于中晚期，失去了手术与根治性放射治疗的机会，只能采用化疗。尽管近年来新的细胞毒性药物及新的联合方案大大地改善了化疗效果与患者耐受性，可是患者个体对治疗的反应与毒性仍然存在较大差异，这种差异不能用患者年龄、伴随疾病、合并用药、肝肾功能状态等因素加以解释。遗传因素是决定药物疗效与毒性的主要因素，识别这些因素是药物遗传学的主要目标。     

肿瘤患者个体化检测化疗的疗效观察

目的探讨根据肿瘤患者个体化检测结果,选择预期敏感药物进行化疗的有效性。方法观察32例肿瘤患者,根据个体化检测结果进行化疗后的疗效、生活质量、不良反应及生存率。结果 32例患者中CR 15.6%(5/32),PR 46.8%(15/32),SD 25.0%(8/32),PD 12.5%(4/32),客观有效率为65.6%(21/32),疾病控制率为87.5%(28/32)。治疗结束后肿瘤标志物水平16例降至正常,9例呈下降趋势,但尚未降至正常,4例无明显变化,3例较治疗前水平升高。所有患者均未出现严重不良反应,治疗后KPS评分明显升高,与治疗前相比差异有统计学意义(P<0.05),治疗后患者饮食及体重增长率分别为71.9%(23/32)和59.4%(19/32)。2例患者因病情进展而死亡。结论根据个体化检测结果进行化疗可明显提高疗效,减轻不良反应。     

代谢组学在肿瘤个体化治疗的研究进展

代谢组学是继基因组学、转录组学和蛋白质组学之后发展起来的一门新的组学方法,也是目前组学研究领域的热点之一.代谢组学以其独特的研究角度和技术优势,迅速而广泛地应用于生命科学的各个研究领域.代谢组学技术在肿瘤个体化治疗领域的应用初步显示出其巨大的潜力和价值.本文就代谢组学的概念、研究内容、研究方法、应用领域,特别是代谢组学在肿瘤个体化治疗研究领域的最新进展和应用前景作一综述.     

肿瘤临床化学治疗的进展

1942年 Gilman,Goodman等试用氮芥治疗淋巴肿瘤及 1 948年 Farber应用氨荃喋呤治疗 1例小儿白血病患者取得成功 ,开创了肿瘤化疗的历史。直至 1 972年美国才开始进行肿瘤内科专科考试并颁发专科证书。继后 ,欧洲在 1 989年首次在伦敦举行肿瘤内科专科资格考试 ,使肿瘤药物治疗成为一个独立的专科 ,从而促进了化学治疗研究的发展。我国从 2 0世纪 80年代末期开始 ,肿瘤临床化疗学科逐步蓬勃发展。不仅临床化疗专科队伍逐渐壮大 ,而且学科水平也在多方面有了明显的进展。1　新的有效化疗药物逐步投入使用我国 2 0世纪 60年代临床使用的化疗…     

与肿瘤个体化诊疗相关的科技计划

随着人类基因组计划、SNP计划和HapMap计划的完成，科学家已基本了解到人类基因组的基因图谱、一级序列、SNPs与其单倍型谱，以及基因表达谱和组学图谱。所有这些图谱都具有明显的个体遗传特征，其中一些则与特定的临床表型紧密联系，这为重大慢性疾病的分子分型和个体化诊疗提供了科学基础，为转换性研究（translational research）提供了可能性。     

分子检测在个体化肿瘤化疗中的意义

 当前肿瘤治疗策略的确立主要是以循证医学证据为基础,虽比单纯依据经验的治疗迈进了一大步,但仍需经过多次调整,方能找到适合每一患者的最佳药物方案及剂量。而相同疾病的不同患者,由于个体遗传学特性的不同,对同一化疗方案的反应性不尽相同,导致疗效差异巨大。依据个体基因型确定药物类别和药物剂量的模式将开创个体化药物治疗的新纪元。     

肿瘤的靶向治疗

靶向治疗通过针对肿瘤特异性的靶点来杀死和抑制肿瘤细胞，避免了对正常细胞的伤害，成为目前肿瘤研究的热点之一。近几年来，靶向治疗新药不断涌现，在许多临床试验或正式临床应用中取得很好的疗效。     

基于基因检测的个体化化疗方案治疗晚期肿瘤

目的 观察根据基因检测结果制定个体化化疗方案治疗晚期肿瘤的疗效.方法 晚期肿瘤非一线治疗的25例患者为研究组,收集患者的手术或穿刺标本,应用测序法检测不同基因mRNA表达水平,筛选最适合的化疗药物,进行个体化治疗.20例根据传统经验及循证医学证据选择治疗方案的患者为对照组.比较两组病例有效率及疾病控制率之间的差异.结果 研究组有效率44％（11/25）,疾病控制率84％（21/25）;对照组有效率15％（3/20）,疾病控制率35％（7/20）.两组差异均有统计学意义（χ2=4.36,P＜ 0.05;χ 2=11.35,P＜0.05）.结论 根据治疗靶标检测结果,对晚期肿瘤患者实施个体化治疗,可能提高有效率,延长患者生存期,值得推广.     

抗肿瘤药物剂量个体化的实用控制方法

许多抗肿瘤药具有治疗指数低的特征,其药代动力学在病人个体间存在较大的差异,而且具有较高毒性。在临床上,对抗肿瘤药实行个体化给药已得到广泛的认同。本文对近年来国内外文献进行归纳分析,介绍剂量优化的几种方法,并对这些方法的原理、在药物治疗中的可行性及其在临床试验和实践中的应用进行了概述总结。     

Personalized medicine for non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is a heterogeneous illness associated with a high mortality rate. Personalized therapy may improve treatment outcomes by identification of a specific genotypic anomaly and target-specific therapy. The most significant development in recent years was the discovery of activated EGF receptor (EGFR) mutations at exons 19 and 21. Patients with EGFR mutations respond dramatically to EGFR tyrosine kinase inhibitors such as gefitinib or erlotinib, resulting in longer progression-free survival. Multiple randomized studies, including the Iressa Pan-Asia Study and WJTOG3405, have confirmed the role of EGFR tyrosine kinase inhibitors as standard first-line therapy for patients with the EGFR mutation. In this article, we summarize the current nonpersonalized therapies and examine the available and investigational personalized therapies for patients with resectable early-stage, unresectable locally advanced, or metastatic disease.     

Personalized medicine for non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is a heterogeneous illness associated with a high mortality rate. Personalized therapy may improve treatment outcomes by identification of a specific genotypic anomaly and target-specific therapy. The most significant development in recent years was the discovery of activated EGF receptor (EGFR) mutations at exons 19 and 21. Patients with EGFR mutations respond dramatically to EGFR tyrosine kinase inhibitors such as gefitinib or erlotinib, resulting in longer progression-free survival. Multiple randomized studies, including the Iressa Pan-Asia Study and WJTOG3405, have confirmed the role of EGFR tyrosine kinase inhibitors as standard first-line therapy for patients with the EGFR mutation. In this article, we summarize the current nonpersonalized therapies and examine the available and investigational personalized therapies for patients with resectable early-stage, unresectable locally advanced, or metastatic disease.     

Personalized immunotherapy in cancer precision medicine

With the significant advances in cancer genomics using next-generation sequencing technologies, genomic and molecular profiling-based precision medicine is used as a part of routine clinical test for guiding and selecting the most appropriate treatments for individual cancer patients. Although many molecular-targeted therapies for a number of actionable genomic alterations have been developed, the clinical application of such information is still limited to a small proportion of cancer patients. In this review, we summarize the current status of personalized drug selection based on genomic and molecular profiling and highlight the challenges how we can further utilize the individual genomic information. Cancer immunotherapies, including immune checkpoint inhibitors, would be one of the potential approaches to apply the results of genomic sequencing most effectively. Highly cancer-specific antigens derived from somatic mutations, the so-called neoantigens, occurring in individual cancers have been in focus recently. Cancer immunotherapies, which target neoantigens, could lead to a precise treatment for cancer patients, despite the challenge in accurately predicting neoantigens that can induce cytotoxic T cells in individual patients. Precise prediction of neoantigens should accelerate the development of personalized immunotherapy including cancer vaccines and T-cell receptor-engineered T-cell therapy for a broader range of cancer patients.     

Personalized medicine in lung cancer: what we need to know

Lung cancer is a complex and often fatal disease. The recent discovery of activating mutations in EGFR and fusion genes involving ALK has set the stage for personalized medicine for lung cancer. Patients selected using biomarkers have benefited from the development of EGFR tyrosine kinase inhibitors and ALK inhibitors with considerable improvement in tumor control and survival. Four key areas of knowledge that are essential to the development of targeted therapy are discussed in this Review: knowing the target, knowing the biomarker, knowing the end point and knowing the mechanisms of resistance.     

Personalized medicine: the road ahead

With breast cancer now being recognized as a heterogeneous disease, the concept of personalized medicine demands that the tumor of every individual be treated uniquely. This has lead to ever-expanding use of existing prognostic and predictive markers, and the search for better ones is ongoing. The classic prognostic tools such as tumor size, lymph node status, grade, hormone receptors, and HER2 status are now supplemented by gene expression-based tools such as PAM50 and MammaPrint. However, the overdependence of these tools on proliferation-related genes is a significant handicap. Although pathway-based signatures hold great promise in future breast cancer prognostication, the fact that every tumor has multiple functional pathways significantly limits the utility of this approach. Developed by the integration of estrogen receptor (ER), HER2, proliferation-related, and other genes, the Oncotype DX assay has been able to provide valuable prognostic information for ER-positive tumors. Newer molecular markers based on cancer stem cells, single-nucleotide polymorphisms (SNPs), and miRNAs are becoming available, but their importance needs to be validated. It is clear that breast cancer is a multifaceted process and that none of the tools can reliably predict a binary outcome (recurrence or no recurrence). The breast cancer community is still awaiting an ideal prognostic tool that can integrate knowledge from classic variables such as tumor size and grade with new throughput technology and principles of pharmacogenomics. Such a tool will not only define prognostic subgroups but also be able to predict therapeutic efficacy and/or resistance based on molecular profiling.     

Personalized medicine: challenge and promise

The new health care buzz words include "personalized or individualized medicine." Populations such as American Indians and Alaska Natives potentially have much to gain from this new science to overcome the known health disparities in these populations. This will require participation and acceptance of diverse populations. This article reviews the promise and challenges of individualizing cancer care using principles of community-based participatory research.