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首页> 外文期刊>Current Cancer Drug Targets >New Indications for Established Drugs: Combined Tumor-Stroma-Targeted Cancer Therapy with PPARγ Agonists, COX-2 Inhibitors, mTOR Antagonists and Metronomic Chemotherapy
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New Indications for Established Drugs: Combined Tumor-Stroma-Targeted Cancer Therapy with PPARγ Agonists, COX-2 Inhibitors, mTOR Antagonists and Metronomic Chemotherapy

机译：既定药物的新适应症：靶向肿瘤间质的癌症治疗与PPARγ激动剂，COX-2抑制剂，mTOR拮抗剂和节律性化学疗法的结合

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In search of new strategies for the treatment of cancer, the interaction between tumor and stroma attracts more and more attention. Disruption of stroma functions, e.g. angiogenesis, has evolved into a promising target for cancer therapies. Since stromal cells are genetically stable, stroma-targeted therapies seem to be less susceptible to the development of drug resistance. Several well-established drugs, which had initially been developed for other indications, also exhibit antitumor activity. Among those, PPARγ agonists, COX-2 inhibitors, and mTOR antagonists are the most remarkable examples. Current research data and clinical experience suggest that these drugs target stroma functions in cancer, in particular angiogenesis, but immunological mechanisms and direct antitumor effects seem to participate as well. In addition to these drugs, frequent administration of low-dose chemotherapeutics, referred to as metronomic chemotherapy, reveals profound anti-angiogenic effects. In the meantime, a multitude of preclinical and clinical studies have been undertaken, which demonstrate the efficacy of these drugs in cancer therapy. Combinatorial use of these agents has been suggested to be superior in terms of antitumor efficacy and prevention of drug resistance. The toxicity of these therapies is surprisingly low compared with conventional high-dose chemotherapy regimens. Patients with advanced disease, often heavily pretreated and presenting multiple drug resistance, could particularly profit from such tumor-stroma-targeted therapies. However, larger randomized clinical trials are required for further evaluation and optimization of this concept.
机译：在寻找治疗癌症的新策略时，肿瘤与基质之间的相互作用越来越受到关注。基质功能的破坏，例如血管生成已经发展成为癌症治疗的有希望的靶标。由于基质细胞在遗传上是稳定的，因此以基质为靶标的疗法似乎不易产生耐药性。最初已开发用于其他适应症的几种成熟药物也具有抗肿瘤活性。其中，最显着的例子是PPARγ激动剂，COX-2抑制剂和mTOR拮抗剂。当前的研究数据和临床经验表明，这些药物靶向癌症中的基质功能，尤其是血管生成，但是免疫学机制和直接的抗肿瘤作用似乎也参与其中。除这些药物外，频繁给药的低剂量化学疗法（称为节律化学疗法）显示出深远的抗血管生成作用。同时，已经进行了大量的临床前和临床研究，证明了这些药物在癌症治疗中的功效。在抗肿瘤功效和预防耐药性方面，已建议将这些药物组合使用是优越的。与常规的大剂量化疗方案相比，这些疗法的毒性令人惊讶地低。患有晚期疾病的患者，通常经过大量的预处理，并表现出多种耐药性，可以从靶向肿瘤基质的治疗中特别受益。但是，需要更大的随机临床试验来进一步评估和优化该概念。

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