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《王子与贫儿》。一个关于抗癌靶向药物的故事。

The prince and the pauper. A tale of anticancer targeted agents.

作者信息

Dueñas-González Alfonso, García-López Patricia, Herrera Luis Alonso, Medina-Franco Jose Luis, González-Fierro Aurora, Candelaria Myrna

机构信息

Unidad de Investigacion Biomédica en Cáncer, Instituto de Investigaciones Biomedicas, UNAM/Instituto Nacional de Cancerologia, Mexico City, Mexico.

出版信息

Mol Cancer. 2008 Oct 23;7:82. doi: 10.1186/1476-4598-7-82.

Abstract

Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consistently failed in the clinical testing. There is however, a characteristic shared by these agents: -their high cost-. This is expected as drug discovery and development is generally carried out within the commercial rather than the academic realm. Given the extraordinarily high therapeutic drug discovery-associated costs and risks, it is highly unlikely that any single public-sector research group will see a novel chemical "probe" become a "drug". An alternative drug development strategy is the exploitation of established drugs that have already been approved for treatment of non-cancerous diseases and whose cancer target has already been discovered. This strategy is also denominated drug repositioning, drug repurposing, or indication switch. Although traditionally development of these drugs was unlikely to be pursued by Big Pharma due to their limited commercial value, biopharmaceutical companies attempting to increase productivity at present are pursuing drug repositioning. More and more companies are scanning the existing pharmacopoeia for repositioning candidates, and the number of repositioning success stories is increasing. Here we provide noteworthy examples of known drugs whose potential anticancer activities have been highlighted, to encourage further research on these known drugs as a means to foster their translation into clinical trials utilizing the more limited public-sector resources. If these drug types eventually result in being effective, it follows that they could be much more affordable for patients with cancer; therefore, their contribution in terms of reducing cancer mortality at the global level would be greater.

摘要

癌症发病率正以惊人的速度上升,从2000年全球1000万新发病例增至2020年的1500万。关于癌症的药物治疗,我们目前正处于两个治疗时代的过渡阶段。所谓的前基因组治疗是指传统的癌症药物,主要是细胞毒性药物类型,而后基因组时代的药物则是指基于理性设计的药物。尽管这种新的药物发现方法有成功的例子,但大多数靶向特异性药物在症状控制和/或生存方面只带来微小的改善,而其他一些药物在临床试验中则一直失败。然而,这些药物有一个共同的特点:它们成本高昂。这是可以预料的,因为药物发现和开发通常是在商业领域而不是学术领域进行的。鉴于与治疗性药物发现相关的成本和风险极高,任何一个公共部门的研究小组都极不可能看到一种新型化学“探针”变成一种“药物”。一种替代的药物开发策略是利用已被批准用于治疗非癌症疾病且其癌症靶点已被发现的现有药物。这种策略也被称为药物重新定位、药物再利用或适应症转换。尽管传统上由于这些药物商业价值有限,大型制药公司不太可能追求开发它们,但目前试图提高生产率的生物制药公司正在进行药物重新定位。越来越多的公司在现有的药典中寻找重新定位的候选药物,成功的重新定位案例数量也在增加。在这里,我们提供了一些已知药物的显著例子,这些药物的潜在抗癌活性已得到突出,以鼓励对这些已知药物进行进一步研究,作为利用更有限的公共部门资源将其转化为临床试验的一种手段。如果这些药物最终被证明是有效的,那么癌症患者使用它们的成本可能会低得多;因此,它们在全球范围内降低癌症死亡率方面的贡献将更大。

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