Potential Successes and Challenges of Targeted Cancer Therapies
Potential Successes and Challenges of Targeted Cancer Therapies
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DOI：
10.1093/jncimonographs/lgz008
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发表时间：
2019-08-01
期刊：
影响因子：
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通讯作者：
Bateman, Emma H.
中科院分区：
文献类型：
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作者：
Keefe, Dorothy M. K.;Bateman, Emma H.
靶向抗癌治疗（TAT）的概念和实现已经存在了至少二十年，并且仍在迅速扩展。很明显，没有治愈癌症的“灵丹妙药”，即使是 TAT 作为单一药物也不太可能成功，需要与化疗、放疗甚至其他靶向药物联合使用。 TAT 尚未实现的另一个承诺是降低毒性。人们认为，通过靶向细胞上或细胞内的受体，而不是细胞周期的特定阶段，TAT 不会产生毒性。然而，事实证明，这些靶标也存在于正常细胞上或正常细胞内，并且非靶标组织上的受体之间甚至存在交叉反应。所有这些都会导致毒性，其机制与药物的作用机制相同，使得减少或预防毒性变得非常困难。这会导致新的靶向治疗产生新的毒性。尽管如此，上述所有因素都不应影响靶向药物所取得的明显成功，这些药物已将几种急性致命的癌症转变为慢性疾病，并使一些迄今为止无法治疗的癌症转变为可治疗的疾病。
The concept and realization of targeted anticancer therapy (TAT) have existed for at least two decades and continue to expand rapidly. It has become clear that there is no "magic bullet" to cure cancer and that even TATs are unlikely to be successful as single agents, necessitating combination with chemotherapy, radiotherapy, or even other targeting agents. The other promise that has not been fulfilled by TAT is that of reduced toxicity. It was thought that by targeting receptors on or within cells, rather than particular phases of the cell cycle, TATs would not be toxic. However, it turns out that the targets also exist on or within normal cells and that there is even cross-reactivity between receptors on nontarget tissues. All of this results in toxicity, the mechanism of which are the same as the mechanism of action of the drugs, making toxicity reduction or prevention very difficult. This leads to new toxicities with new targeted treatments. Nevertheless, all of the above should not detract from the obvious successes of targeted agents, which have turned several acutely fatal cancers into chronic diseases and rendered some hitherto untreatable cancers into treatable diseases.