Letai Anthony, de The Hugues
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Nat Rev Cancer. 2025 Mar;25(3):209-218. doi: 10.1038/s41568-024-00778-4. Epub 2024 Dec 16.
In recent decades, millions of patients with cancer have been cured by chemotherapy alone. By 'cure', we mean that patients with cancers that would be fatal if left untreated receive a time-limited course of chemotherapy and their cancer disappears, never to return. In an era when hundreds of thousands of cancer genomes have been sequenced, a remarkable fact persists: in most patients who have been cured, we still do not fully understand the mechanisms underlying the therapeutic index by which the tumour cells are killed, but normal cells are somehow spared. In contrast, in more recent years, patients with cancer have benefited from targeted therapies that usually do not cure but whose mechanisms of therapeutic index are, at least superficially, understood. In this Perspective, we will explore the various and sometimes contradictory models that have attempted to explain why chemotherapy can cure some patients with cancer, and what gaps in our understanding of the therapeutic index of chemotherapy remain to be filled. We will summarize principles which have benefited curative conventional chemotherapy regimens in the past, principles which might be deployed in constructing combinations that include modern targeted therapies.
近几十年来，数百万癌症患者仅通过化疗就被治愈了。这里所说的“治愈”，是指那些如果不治疗就会致命的癌症患者接受了一个疗程有限的化疗后，癌症消失且不再复发。在一个已经对数十万癌症基因组进行测序的时代，一个显著的事实依然存在：在大多数被治愈的患者中，我们仍然没有完全理解肿瘤细胞被杀死而正常细胞却能幸免的治疗指数背后的机制。相比之下，近年来，癌症患者受益于靶向治疗，靶向治疗通常无法治愈癌症，但至少从表面上看，我们理解其治疗指数的机制。在这篇观点文章中，我们将探讨各种有时相互矛盾的模型，这些模型试图解释化疗为何能治愈一些癌症患者，以及我们对化疗治疗指数的理解中仍有待填补的空白。我们将总结过去有益于根治性传统化疗方案的原则，以及可能用于构建包含现代靶向治疗的联合治疗方案的原则。
