Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), Heidelberg, Germany.
Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
J Exp Med. 2021 Jan 4;218(1). doi: 10.1084/jem.20190218.
Historically, therapy of metastatic disease has essentially been limited to using strategies that were identified and established to shrink primary tumors. The limited efficacy of such treatments on overall patient survival stems from diverging intrinsic and extrinsic characteristics of a primary tumor and metastases originating therefrom. To develop better therapeutic strategies to treat metastatic disease, there is an urgent need to shift the paradigm in preclinical metastasis research by conceptualizing metastatic dissemination, colonization, and growth as spatiotemporally dynamic processes and identifying rate-limiting vulnerabilities of the metastatic cascade. Clinically, while metastatic colonization remains the most attractive therapeutic avenue, comprehensive understanding of earlier steps may unravel novel metastasis-restricting therapies for presurgical neoadjuvant application. Moving beyond a primary tumor-centric view, this review adopts a holistic approach to understanding the spatial and temporal progression of metastasis. After reviewing recent developments in metastasis research, we highlight some of the grand challenges and propose a framework to expedite mechanism-based discovery research feeding the translational pipeline.
从历史上看，转移性疾病的治疗基本上仅限于使用那些被确定和确立的策略来缩小原发性肿瘤。这些治疗方法对患者总体生存的疗效有限，是因为原发性肿瘤和由此产生的转移灶的内在和外在特征不同。为了开发更好的治疗转移性疾病的治疗策略，迫切需要通过将转移传播、定植和生长概念化为时空动态过程，并确定转移级联的限速弱点，来改变临床前转移研究的范例。临床上，虽然转移性定植仍然是最有吸引力的治疗途径，但对早期步骤的全面了解可能会为术前新辅助应用揭开新的限制转移的治疗方法。本综述超越了以原发性肿瘤为中心的观点，采用整体方法来理解转移的时空进展。在回顾了转移研究的最新进展之后，我们强调了一些重大挑战，并提出了一个框架，以加速转化管道的基于机制的发现研究。
