Kamińska Katarzyna, Czarnecka Anna M, Escudier Bernard, Lian Fei, Szczylik Cezary
Department of Oncology, Military Institute of Medicine, Warsaw, Poland.
Department of Oncology, Military Institute of Medicine, Warsaw, Poland.
Urol Oncol. 2015 Nov;33(11):476-85. doi: 10.1016/j.urolonc.2015.07.010. Epub 2015 Aug 18.
Our knowledge on the molecular basis of kidney cancer metastasisis still relatively low. About 25-30% of patients suffering from clear cell renal cell carcinoma (ccRCC)present metastatic disease at the time of primary diagnosis. Only 10% of patients diagnosed with stage IV disease survive 5 years and 20-50% of patients diagnosed with localized tumor develop metastases within 3 years. High mortality of patients with this cancer is associated with a large potential for metastasis and resistance to oncologic treatments such as chemo- and radiotherapy. Literature data based on studies conducted on other types of cancers suggest that in metastatic ccRCC, the complex of interleukin-6 (IL-6) and its soluble receptor (sIL-6R; complex IL-6/sIL-6R) and the signal transduction pathway (gp130/STAT3) might play a key role in this process.
Therefore, in this review we focus on the role of IL-6 and its signaling pathways as a factor for development and spread of RCC. Analyzing the molecular basis of cancer spreading will enable the development of prognostic tests, evaluate individual predisposition for metastasis, and produce drugs that target metastases. As the development of effective systemic treatments evolve from advancements in molecular biology, continued studies directed at understanding the genetic and molecular complexities of this disease are critical to improve RCC treatment options.
我们对肾癌转移分子基础的了解仍然相对较少。约25%-30%的透明细胞肾细胞癌(ccRCC)患者在初次诊断时就已出现转移性疾病。只有10%的IV期疾病患者能存活5年,而20%-50%诊断为局限性肿瘤的患者会在3年内发生转移。这种癌症患者的高死亡率与转移潜力大以及对化疗和放疗等肿瘤治疗的耐药性有关。基于对其他类型癌症研究的文献数据表明,在转移性ccRCC中,白细胞介素-6(IL-6)及其可溶性受体(sIL-6R;IL-6/sIL-6R复合物)以及信号转导通路(gp130/STAT3)可能在这一过程中起关键作用。
因此,在本综述中,我们重点关注IL-6及其信号通路作为RCC发生和扩散因素的作用。分析癌症扩散的分子基础将有助于开发预后检测方法,评估个体转移易感性,并生产针对转移的药物。由于有效的全身治疗的发展源于分子生物学的进步,持续开展旨在了解该疾病遗传和分子复杂性的研究对于改善RCC治疗方案至关重要。