Current treatments for clear cell renal cell cancer (ccRCC) are insufficient because two-thirds of patients with metastases progress within two years. Here we report the identification and characterization of a cancer stem cell (CSC) population in ccRCC. CSCs are quantitatively correlated with tumor aggressiveness and metastasis. Transcriptional profiling and single cell sequencing reveal that these CSCs exhibit an activation of WNT and NOTCH signaling. A significant obstacle to the development of rational treatments has been the discrepancy between model systems and the in vivo situation of patients. To address this, we use CSCs to establish non-adherent sphere cultures, 3D tumor organoids, and xenografts. Treatment with WNT and NOTCH inhibitors blocks the proliferation and self-renewal of CSCs in sphere cultures and organoids, and impairs tumor growth in patient-derived xenografts in mice. These findings suggest that our approach is a promising route towards the development of personalized treatments for individual patients.

中文翻译：

---

在肾癌干细胞中抑制WNT和NOTCH及其对人类患者的影响。

由于三分之二的转移性患者在两年内进展，因此目前对透明细胞肾细胞癌（ccRCC）的治疗还不够。在这里，我们报告ccRCC中的癌症干细胞（CSC）人口的鉴定和表征。CSC与肿瘤的侵袭性和转移在数量上相关。转录谱和单细胞测序表明，这些CSC表现出WNT和NOTCH信号的激活。发展合理疗法的一个重大障碍是模型系统与患者体内状况之间的差异。为了解决这个问题，我们使用CSC建立非粘附球培养，3D肿瘤类器官和异种移植。使用WNT和NOTCH抑制剂处理会阻止CSC在球形培养物和类器官中的增殖和自我更新，并损害小鼠患者异种移植物中的肿瘤生长。这些发现表明，我们的方法是针对个别患者开发个性化治疗的有希望的途径。