Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 N. 15(th) Street, Philadelphia, PA, USA.
Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 N. 15(th) Street, Philadelphia, PA, USA; Program in Prostate Cancer, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Pharmacol Ther. 2019 Jul;199:117-128. doi: 10.1016/j.pharmthera.2019.03.007. Epub 2019 Mar 12.
Here we propose that therapeutic targeting of circulating tumor cells (CTCs), which are widely understood to be the seeds of metastasis, would represent an effective strategy towards limiting numerical expansion of secondary lesions and containing overall tumor burden in cancer patients. However, the molecular mediators of tumor seeding have not been well characterized. This is in part due to the limited number of pre-clinical in vivo approaches that appropriately interrogate the mechanisms by which cancer cells home to arresting organs. It is critical that we continue to investigate the mediators of tumor seeding as it is evident that the ability of CTCs to colonize in distant sites is what drives disease progression even after the primary tumor has been ablated by local modalities. In addition to slowing disease progression, containing metastatic spread by impeding tumor cell seeding may also provide a clinical benefit by increasing the duration of the residence of CTCs in systemic circulation thereby increasing their exposure to pharmacological agents commonly used in the treatment of patients such as chemotherapy and immunotherapies. In this review we will examine the current state of knowledge about the mechanisms of tumor cells seeding as well as explore how targeting this stage of metastatic spreading may provide therapeutic benefit to patients with advanced disease.
在这里，我们提出治疗循环肿瘤细胞（CTCs），这些细胞被广泛认为是转移的种子，将代表一种限制继发性病变数量扩张和控制癌症患者总体肿瘤负担的有效策略。然而，肿瘤播种的分子介质尚未得到很好的描述。这部分是由于适当询问癌细胞归巢到阻滞器官的机制的临床前体内方法数量有限。继续研究肿瘤播种的介质非常重要，因为显然即使通过局部方式消融原发性肿瘤后，CTC 在远处定植的能力也会驱动疾病进展。除了减缓疾病进展外，通过阻碍肿瘤细胞播种来控制转移扩散也可能通过增加 CTC 在全身循环中的停留时间从而增加它们暴露于化学疗法和免疫疗法等常用于治疗患者的药物来提供临床益处。在这篇综述中，我们将检查目前关于肿瘤细胞播种机制的知识状况，并探讨靶向转移扩散的这个阶段如何为晚期疾病患者提供治疗益处。
