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Cancer therapy: Attempt cure or manage drug resistance?

机译:癌症治疗:尝试治愈或管理耐药性?

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摘要

Cancer treatment is often aimed at achieving rapid, large, and sustained reductions in tumor burden. Even when these strong responses are achieved, treatment frequently fails due to the emergence of drug‐resistant cell lineages. Over the last decade, a variety of authors have suggested that treatment should instead be aimed at containing resistance rather than curing the patient. That new philosophy poses a dilemma: how to choose between treatment regimens that can sometimes cure the patient and regimens that can delay progression but not cure the patient? Here, we investigate that choice. We define aspects of the evolution and ecology of tumor dynamics that determine whether it is better to attempt cure or to manage resistance. Even when it is possible to manage resistance and delay progression, this may not be the best treatment option. We show that the best option depends on how “cure” and “delaying progression” are prioritized, and how those priorities will vary among patients. We also discuss the difficulties of comparing in clinical trials traditional strategies that can sometimes successfully cure to alternative approaches where cure is not possible. More generally, where resistance management is possible, there are new challenges in communicating options to patients, setting treatment guidelines, and evaluating data from clinical trials.
机译:癌症治疗通常旨在实现肿瘤负担的快速,大,持续减少。即使实现了这些强烈的反应,治疗常常由于耐药细胞谱系的出现而常常失败。在过去十年中,各种作者提出了治疗,而是旨在含有抗性而不是固化患者。新哲学造成困境:如何在治疗方案之间进行选择,有时可以治愈患者和可以延迟进展但不治愈患者的治疗方案?在这里,我们调查该选择。我们定义了肿瘤动态的演变和生态学的方面,以确定是否更好地尝试治愈或抵抗。即使有可能管理阻力和延迟进展,也可能不是最好的治疗选项。我们表明最好的选择取决于“治愈”和“延迟进展”的优先事项,以及这些优先级如何在患者中变化。我们还讨论了在临床试验中比较的困难,这些策略有时可以成功地治愈治愈的替代方法。更一般地,在可能的情况下,在可能的情况下,对患者的选择,设定治疗准则和评估来自临床试验的数据存在新的挑战。

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