Schiavoni Valentina, Emanuelli Monica, Milanese Giulio, Galosi Andrea Benedetto, Pompei Veronica, Salvolini Eleonora, Campagna Roberto
Department of Clinical Sciences, Polytechnic University of Marche, 60020 Ancona, Italy.
New York-Marche Structural Biology Center (NY-MaSBiC), Polytechnic University of Marche, 60131 Ancona, Italy.
Int J Mol Sci. 2024 Dec 10;25(24):13239. doi: 10.3390/ijms252413239.
Renal cell carcinoma (RCC) is the most common type of kidney cancer arising from renal tubular epithelial cells and is characterized by a high aggressive behavior and invasiveness that lead to poor prognosis and high mortality rate. Diagnosis of RCC is generally incidental and occurs when the stage is advanced and the disease is already metastatic. The management of RCC is further complicated by an intrinsic resistance of this malignancy to chemotherapy and radiotherapy, which aggravates the prognosis. For these reasons, there is intense research focused on identifying novel biomarkers which may be useful for a better prognostic assessment, as well as molecular markers which could be utilized for targeted therapy. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that has been identified as a key modulator of oxidative stress response, and its overexpression is considered a negative prognostic feature in several types of cancers including RCC, since it is involved in various key cancer-promoting functions such as proliferation, anabolic metabolism and resistance to chemotherapy. Given the key role of Nrf2 in promoting tumor progression, this enzyme could be a promising biomarker for a more accurate prediction of RCC course and it can also represent a valuable therapeutic target. In this review, we provide a comprehensive literature analysis of studies that have explored the role of Nrf2 in RCC, underlining the possible implications for targeted therapy.
肾细胞癌（RCC）是起源于肾小管上皮细胞的最常见的肾癌类型，其特点是具有高度侵袭性和浸润性，导致预后不良和死亡率高。RCC的诊断通常是偶然的，发生在疾病进展到晚期且已经发生转移时。这种恶性肿瘤对化疗和放疗具有内在抗性，这使得RCC的治疗更加复杂，从而加重了预后情况。基于这些原因，人们正在进行深入研究，重点是寻找可能有助于更好地进行预后评估的新型生物标志物，以及可用于靶向治疗的分子标志物。核因子红细胞2相关因子2（Nrf2）是一种转录因子，已被确定为氧化应激反应的关键调节因子，其过表达在包括RCC在内的几种癌症中被认为是不良预后特征，因为它参与了多种关键的癌症促进功能，如增殖、合成代谢和化疗抗性。鉴于Nrf2在促进肿瘤进展中的关键作用，这种酶可能是更准确预测RCC病程的有前景的生物标志物，并且它也可以代表一个有价值的治疗靶点。在这篇综述中，我们对探索Nrf2在RCC中的作用的研究进行了全面的文献分析，强调了其对靶向治疗的可能影响。
