下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Combination Therapies for Advanced Biliary Tract Cancer.
胆道癌(BTCs)是一组近期发病率上升且预后较差的恶性肿瘤。
胆道癌(BTCs)是一组近期发病率上升且预后较差的恶性肿瘤。手术是唯一的治愈性疗法。然而,由于诊断时多处于晚期且疾病进展迅速,大多数患者仅适合接受姑息治疗。目前晚期BTC的一线治疗是吉西他滨联合顺铂化疗。尽管如此,许多患者对该方案产生耐药。多年来,鲜有化疗方案能够改善患者的总生存期。因此,靶向治疗等新型疗法已被引入用于治疗该患者群体。对BTC肿瘤发生和基因谱的广泛研究揭示了其异质性及潜在靶向通路,如EGFR、VEGF、MEK/ERK、PI3K和mTOR。此外,突变分析已记录了IDH1、FGFR2、HER2、PRKACA、PRKACB、BRAF和KRAS基因异常的存在。近年来免疫治疗的出现拓展了这类恶性肿瘤的治疗格局。癌症疫苗、过继性细胞转移和免疫检查点抑制剂已在BTC试验中进行了广泛研究。因此,患者分层及多种疗法的联合已成为改善患者预后的合理且重要的临床策略。本综述详细阐述了近年来关于晚期BTC联合治疗策略的文献及正在进行的临床试验,以期为晚期BTC的治疗提供新的启示。
Biliary tract cancers (BTCs) are a group of malignant neoplasms that have recently increased in incidence and have a poor prognosis. Surgery is the only curative therapy. However, most patients are only indicated for palliative therapy because of advanced-stage disease at diagnosis and rapid progression. The current first-line treatment for advanced BTC is gemcitabine and cisplatin chemotherapy. Nonetheless, many patients develop resistance to this regimen. Over the years, few chemotherapy regimens have managed to improve the overall survival of patients. Accordingly, novel therapies such as targeted therapy have been introduced to treat this patient population. Extensive research on tumorigenesis and the genetic profiling of BTC have revealed the heterogenicity and potential target pathways, such as EGFR, VEGF, MEK/ERK, PI3K and mTOR. Moreover, mutational analysis has documented the presence of IDH1 , FGFR2 , HER2 , PRKACA , PRKACB , BRAF , and KRAS gene aberrations. The emergence of immunotherapy in recent years has expanded the treatment landscape for this group of malignancies. Cancer vaccines, adoptive cell transfer, and immune checkpoint inhibitors have been extensively investigated in trials of BTC. Therefore, patient stratification and a combination of various therapies have become a reasonable and important clinical strategy to improve patient outcomes. This review elaborates the literature on combined treatment strategies for advanced BTC from the past few years and ongoing clinical trials to provide new inspiration for the treatment of advanced BTC.
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