Lian Bi-Jun, Zhang Ke, Fang Xu-Dong, Li Feng, Dai Zhao, Chen Wei-Ying, Qi Xiao-Ping
Department of Oncologic and Urologic Surgery, The 903rd People's Liberation Army (PLA) Hospital, Wenzhou Medical University, Hangzhou, China.
Center for Radiation Oncology, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Oncol. 2022 Jul 6;12:927250. doi: 10.3389/fonc.2022.927250. eCollection 2022.
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. The top four mutant genes affecting the occurrence and progression of ccRCC are , and , respectively. Tyrosine kinase/mammalian target of rapamycin inhibitors (TKI/mTORis) with or without immunotherapy are the standard and effective therapy to metastatic ccRCC. Once TKI/mTORis fail to ccRCC, there is still a lack of other effective therapies. In this study, we reported a case in which a metastatic ccRCC patient (T2aN1M1) presented resistance after a 28-month treatment by sorafenib-axitinib-everolimus (TKI-TKI-mTORi). Subsequently, a frame shift pathogenic mutation, c.799_800del (p.Q267fs) in the exon10 of in ccRCC, was revealed by targeted sequencing. Oral administration of nilapanib (PARP inhibitor) was further given, which may provide a new therapy for TKI/mTORi-resistance metastatic ccRCC. Fortunately, a partial response has been achieved and lasted for 5 months. Since the frequency of mutations in ccRCC patients was approximately 10%-20%, as reported previously, we also tried to explore the potential mechanisms benefitting from the nilapanib. Moreover, the literature concerning mutation and associated cancers including ccRCC is reviewed.
透明细胞肾细胞癌（ccRCC）是肾癌最常见的亚型。影响ccRCC发生和进展的前四个突变基因分别是 、 和 。酪氨酸激酶/雷帕霉素哺乳动物靶点抑制剂（TKI/mTORi）联合或不联合免疫疗法是转移性ccRCC的标准有效治疗方法。一旦TKI/mTORi对ccRCC治疗失败，仍然缺乏其他有效疗法。在本研究中，我们报告了1例转移性ccRCC患者（T2aN1M1）在接受索拉非尼 - 阿昔替尼 - 依维莫司（TKI - TKI - mTORi）治疗28个月后出现耐药的病例。随后，通过靶向测序在ccRCC的 外显子10中发现了一个移码致病性突变，即c.799_800del（p.Q267fs）。进一步给予尼拉帕尼（PARP抑制剂）口服，这可能为TKI/mTORi耐药的转移性ccRCC提供一种新的治疗方法。幸运的是，已取得部分缓解并持续了5个月。如先前报道，由于ccRCC患者中 突变的频率约为10% - 20%，我们还试图探索从尼拉帕尼中获益的潜在机制。此外，还对有关 突变及包括ccRCC在内的相关癌症的文献进行了综述。
