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使用针对 NSCLC 患者的无治疗选择的通用靶向治疗多药物方案进行肿瘤学试验的设计原理(综述)。

Rationale for the design of an oncology trial using a generic targeted therapy multi‑drug regimen for NSCLC patients without treatment options (Review).

机构信息

Life Science Consulting, Schloss Pesch, D‑40668 Meerbusch, Germany.

出版信息

Oncol Rep. 2013 Oct;30(4):1535-41. doi: 10.3892/or.2013.2631. Epub 2013 Jul 22.

Abstract

Despite more than 70 years of research concerning medication for cancer treatment, the disease still remains one of the leading causes of mortality worldwide. Many cancer types lead to death within a period of months to years. The original class of chemotherapeutics is not selective for tumor cells and often has limited efficacy, while treated patients suffer from adverse side‑effects. To date, the concept of tumor‑specific targeted therapy drugs has not fulfilled its expectation to provide a key for a cure. Today, many oncology trials are designed using a combination of chemotherapeutics with targeted therapy drugs. However, these approaches have limited outcomes in most cancer indications. This perspective review provides a rationale to combine targeted therapy drugs for cancer treatment based on observations of evolutionary principles of tumor development and HIV infections. In both diseases, the mechanisms of immune evasion and drug resistance can be compared to some extent. However, only for HIV is a breakthrough treatment available, which is the highly active antiretroviral therapy (HAART). The principles of HAART and recent findings from cancer research were employed to construct a hypothetical model for cancer treatment with a multi‑drug regimen of targeted therapy drugs. As an example of this hypothesis, it is proposed to combine already marketed targeted therapy drugs against VEGFRs, EGFR, CXCR4 and COX2 in an oncology trial for non‑small cell lung cancer patients without further treatment options.

摘要

尽管针对癌症治疗的药物研究已经进行了 70 多年,但这种疾病仍然是全球主要的死亡原因之一。许多癌症类型在数月至数年内导致死亡。最初的一类化疗药物对肿瘤细胞没有选择性,通常疗效有限,而接受治疗的患者则会遭受不良反应。迄今为止,肿瘤特异性靶向治疗药物的概念并没有达到治愈的预期。如今,许多肿瘤学临床试验采用化疗药物与靶向治疗药物联合治疗。然而,在大多数癌症适应症中,这些方法的效果有限。本文综述基于肿瘤发展和 HIV 感染的进化原则观察,为癌症治疗中联合靶向治疗药物提供了一个合理的依据。在这两种疾病中,免疫逃逸和耐药性的机制在某种程度上可以进行比较。然而,只有 HIV 有可用的突破性治疗方法,即高效抗逆转录病毒疗法(HAART)。我们借鉴了 HAART 的原则和癌症研究的最新发现,构建了一个假设的癌症治疗模型,使用靶向治疗药物的多药物方案。作为该假设的一个例子,提议在非小细胞肺癌患者的肿瘤学临床试验中联合已经上市的针对 VEGFR、EGFR、CXCR4 和 COX2 的靶向治疗药物,这些患者没有其他治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ec/3810357/0fca3ffd20b7/OR-30-04-1535-g00.jpg

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