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

机译:王子和贫民窟。抗癌靶向药物的故事

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摘要

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.
机译:癌症的发生率将以惊人的速度增长,从2000年的全球1000万新病例增加到2020年的1500万。关于癌症的药物治疗,我们目前处于两个治疗时代的过渡时期。所谓的基因组前治疗,指的是传统的癌症药物,主要是细胞毒性药物类型,而基因组后的时代型药物是指基于合理设计的药物。尽管有这种新型药物发现方法的成功实例,但是大多数靶标特异性药物只能在症状控制和/或生存方面提供很小的收益,而其他药物在临床测试中一直失败。但是,这些代理具有一个共同的特征:-它们的高成本-。这是可以预期的,因为药物的发现和开发通常是在商业领域而不是学术领域内进行的。鉴于与治疗药物发现相关的成本和风险异常高,任何一个公共部门研究小组都不太可能将新型化学“探针”变成“药物”。另一种药物开发策略是开发已被批准用于治疗非癌性疾病且已发现其癌症靶标的既定药物。此策略也称为药物重新定位,药物重新定位或指示转换。尽管Big Pharma传统上由于其商业价值有限而不太可能进行这些药物的开发,但目前试图提高生产率的生物制药公司正在寻求药物重新定位。越来越多的公司正在扫描现有药典以重新定位候选对象,并且重新定位成功案例的数量也在增加。在这里,我们提供了一些值得注意的已知药物实例,这些药物已经强调了其潜在的抗癌活性,以鼓励人们对这些已知药物进行进一步的研究,以此作为利用有限的公共部门资源促进其转化为临床试验的一种手段。如果这些药物最终导致有效,那么对于癌症患者来说,它们可能会更便宜。因此,它们在降低全球癌症死亡率方面的贡献将更大。

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