Department of Urology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Int J Oncol. 2021 Jul;59(1). doi: 10.3892/ijo.2021.5228. Epub 2021 May 26.
Sunitinib is widely used as a first‑line treatment for advanced renal cell carcinoma (RCC). However, a number of patients with RCC who receive sunitinib develop drug resistance; and the biological mechanisms involved in resistance to sunitinib remain unclear. It has previously been suggested that the protein glutaminyl‑peptide cyclotransferase (QPCT) is closely related to sunitinib resistance in RCC. Thus, in the present study, in order to further examine the molecular mechanisms responsible for sunitinib resistance in RCC, sunitinib‑non‑responsive and ‑responsive RCC tissue and plasma samples were collected and additional experiments were performed in order to elucidate the molecular mechanisms responsible for sunitinib resistance in RCC. The upstream and downstream regulatory mechanisms of QPCT were also evaluated. On the whole, the data from the present study suggest that QPCT, CCCTC‑binding factor (CTCF) and phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (PIK3CA) may be used as targets for predicting, reversing and treating sunitinib‑resistant RCC.
舒尼替尼被广泛用作晚期肾细胞癌 (RCC) 的一线治疗药物。然而,许多接受舒尼替尼治疗的 RCC 患者会产生耐药性;而涉及舒尼替尼耐药的生物学机制尚不清楚。先前有研究表明,谷氨酰胺肽环转移酶 (QPCT) 与 RCC 中的舒尼替尼耐药密切相关。因此,在本研究中,为了进一步探讨导致 RCC 舒尼替尼耐药的分子机制,收集了舒尼替尼耐药和敏感的 RCC 组织和血浆样本,并进行了额外的实验,以阐明导致 RCC 舒尼替尼耐药的分子机制。还评估了 QPCT 的上游和下游调节机制。总的来说,本研究的数据表明,QPCT、CCCTC 结合因子 (CTCF) 和磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚单位 α (PIK3CA) 可用作预测、逆转和治疗舒尼替尼耐药 RCC 的靶点。