Translational Breast Cancer Program, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.
School of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australia.
Nat Rev Clin Oncol. 2019 Mar;16(3):185-204. doi: 10.1038/s41571-018-0134-8.
Most cancer-related deaths are a result of metastasis, and thus the importance of this process as a target of therapy cannot be understated. By asking 'how can we effectively treat cancer?', we do not capture the complexity of a disease encompassing >200 different cancer types - many consisting of multiple subtypes - with considerable intratumoural heterogeneity, which can result in variable responses to a specific therapy. Moreover, we have much less information on the pathophysiological characteristics of metastases than is available for the primary tumour. Most disseminated tumour cells that arrive in distant tissues, surrounded by unfamiliar cells and a foreign microenvironment, are likely to die; however, those that survive can generate metastatic tumours with a markedly different biology from that of the primary tumour. To treat metastasis effectively, we must inhibit fundamental metastatic processes and develop specific preclinical and clinical strategies that do not rely on primary tumour responses. To address this crucial issue, Cancer Research UK and Cancer Therapeutics CRC Australia formed a Metastasis Working Group with representatives from not-for-profit, academic, government, industry and regulatory bodies in order to develop recommendations on how to tackle the challenges associated with treating (micro)metastatic disease. Herein, we describe the challenges identified as well as the proposed approaches for discovering and developing anticancer agents designed specifically to prevent or delay the metastatic outgrowth of cancer.
大多数与癌症相关的死亡都是转移的结果，因此，不能低估这一过程作为治疗靶点的重要性。通过问“我们如何有效地治疗癌症？”，我们无法捕捉到涵盖>200 种不同癌症类型的疾病的复杂性——其中许多类型由多个亚型组成，具有相当大的肿瘤内异质性，这可能导致对特定治疗的反应不同。此外，我们对转移的病理生理特征的了解远不如对原发性肿瘤的了解。大多数到达远处组织的播散性肿瘤细胞，被陌生的细胞和外来的微环境包围，很可能死亡；然而，那些存活下来的细胞可以产生具有明显不同于原发性肿瘤生物学特性的转移性肿瘤。为了有效地治疗转移，我们必须抑制基本的转移过程，并开发不依赖于原发性肿瘤反应的特定临床前和临床策略。为了解决这个关键问题，英国癌症研究中心和澳大利亚癌症治疗研究中心成立了一个转移工作组，成员来自非营利组织、学术机构、政府、工业界和监管机构，以制定如何应对治疗（微）转移性疾病相关挑战的建议。在此，我们描述了确定的挑战以及发现和开发专门用于预防或延迟癌症转移生长的抗癌药物的建议方法。
