A framework for understanding and targeting residual disease in oncogene-driven solid cancers.
A framework for understanding and targeting residual disease in oncogene-driven solid cancers.
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DOI：
10.1038/nm.4091
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发表时间：
2016-05-05
期刊：
影响因子：
82.9
通讯作者：
Doebele RC
中科院分区：
文献类型：
--
作者：
Bivona TG;Doebele RC
分子靶向治疗有可能大大提高癌症患者的生存率。然而，在晚期实体癌患者中，靶向治疗的完全和持久反应是罕见的。即使是最有效的靶向治疗通常也不能诱导完全的肿瘤反应，导致残留疾病和肿瘤进展，限制了患者的生存。我们讨论了新出现的需要，以更充分地了解残留疾病的分子基础，作为设计原则性治疗策略的前奏，以最大限度地减少或消除它，以便我们可以从暂时转向慢性控制或治愈晚期实体癌患者。最终，我们提出了一个转变，从目前的反应范式的分析和治疗获得性耐药的先发制人的范式定义残留疾病的机制，以目标和限制这种疾病水库。
Molecular targeted therapy has the potential to dramatically improve cancer patient survival. However, complete and durable responses to targeted therapy are rare in advanced-stage solid cancer patients. Even the most effective targeted therapies generally do not induce a complete tumor response, resulting in residual disease and tumor progression that limits patient survival. We discuss the emerging need to more fully understand the molecular basis of residual disease as a prelude to designing principled therapeutic strategies to minimize or eliminate it so that we can move from temporary to chronic control or cure in advanced-stage solid cancer patients. Ultimately, we propose a shift from the current reactive paradigm of analyzing and treating acquired drug resistance to a pre-emptive paradigm of defining the mechanisms of residual disease in order to target and limit this disease reservoir.