Drug rechallenge and treatment beyond progression--implications for drug resistance.
Drug rechallenge and treatment beyond progression--implications for drug resistance.
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药物补偿和治疗超出进展 - 耐药性的刺激性。
DOI：
10.1038/nrclinonc.2013.158
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Kerbel RS
中科院分区：
文献类型：
--
作者：
Kuczynski EA;Sargent DJ;Grothey A;Kerbel RS
肿瘤治疗复发性或难治性疾病的既定教条表明，在疾病进展时改变治疗方法，因为假定癌症已具有耐药性。耐药性，无论是预先存在的还是后天获得的，在很大程度上被认为是一个稳定和可遗传的过程；因此，重复使用失败的治疗药物通常是禁忌的。在过去的几十年里，临床证据表明，与化疗和靶向药物有关的获得性耐药的不稳定，非遗传机制的作用。在许多情况下，患者在治疗期间疾病复发或进展后的药物休息期后对重新引入相同的治疗（药物再挑战）有反应。另外，尽管有限，证据表明，在某些情况下，在疾病进展之后继续治疗也可以具有抗肿瘤活性。在这篇综述中，我们描述了这些治疗策略中使用的抗癌药物，并讨论了重新引入或继续治疗后肿瘤明显再致敏的潜在机制。大量的恶性肿瘤和药物挑战了在每条治疗线上永久切换到不同药物的习俗，需要对疾病进展和耐药性的定义以及由此产生的对患者护理的影响进行更深入的检查。
The established dogma in oncology for managing recurrent or refractory disease dictates that therapy is changed at disease progression, because the cancer is assumed to have become drug-resistant. Drug resistance, whether pre-existing or acquired, is largely thought to be a stable and heritable process; thus, reuse of therapeutic agents that have failed is generally contraindicated. Over the past few decades, clinical evidence has suggested a role for unstable, non-heritable mechanisms of acquired drug resistance pertaining to chemotherapy and targeted agents. There are many examples of circumstances where patients respond to reintroduction of the same therapy (drug rechallenge) after a drug holiday following disease relapse or progression during therapy. Additional, albeit limited, evidence suggests that, in certain circumstances, continuing a therapy beyond disease progression can also have antitumour activity. In this Review, we describe the anticancer agents used in these treatment strategies and discuss the potential mechanisms explaining the apparent tumour re-sensitization with reintroduced or continued therapy. The extensive number of malignancies and drugs that challenge the custom of permanently switching to different drugs at each line of therapy warrants a more in-depth examination of the definitions of disease progression and drug resistance and the resulting implications for patient care.