The proliferation rate paradox in antimitotic chemotherapy.
The proliferation rate paradox in antimitotic chemotherapy.
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DOI：
10.1091/mbc.e10-04-0335
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发表时间：
2012-01
影响因子：
3.3
通讯作者：
Mitchison TJ
中科院分区：
文献类型：
--
作者：
Mitchison TJ
细胞毒性癌症化疗药物被认为通过靶向快速增殖的细胞来获得选择性。然而，在许多化学敏感的人类癌症中，增殖率很低，目前还不清楚仅杀死分裂细胞的药物如何促进肿瘤消退。四个潜在的解决方案，这种“增殖率悖论”的微管稳定药物紫杉醇进行了讨论：药物保留在肿瘤中，杀死静止细胞，靶向肿瘤中的非癌细胞，和旁观者效应。测试这些潜在的药物作用机制将有助于合理地改善抗有丝分裂化疗，也许更普遍的细胞毒性化疗。
Cytotoxic cancer chemotherapy drugs are believed to gain selectivity by targeting cells that proliferate rapidly. However, the proliferation rate is low in many chemosensitive human cancers, and it is not clear how a drug that only kills dividing cells could promote tumor regression. Four potential solutions to this “proliferation rate paradox” are discussed for the microtubule-stabilizing drug paclitaxel: drug retention in tumors, killing of quiescent cells, targeting of noncancer cells in the tumor, and bystander effects. Testing these potential mechanisms of drug action will facilitate rational improvement of antimitotic chemotherapy and perhaps cytotoxic chemotherapy more generally.