Tsumura Takehiko, Doi Keitaro, Marusawa Hiroyuki
Department of Medical Oncology, Osaka Red Cross Hospital, Osaka 543-8555, Japan.
Department of Gastroenterology, Osaka Red Cross Hospital, Osaka 543-8555, Japan.
Cancers (Basel). 2022 Jul 28;14(15):3674. doi: 10.3390/cancers14153674.
Tumor-agnostic precision medicine employing comprehensive genome profiling (CGP) and using next-generation sequencing (NGS) has been progressing recently. This review focuses on precision medicine for advanced unresectable hepatobiliary and pancreatic cancers. In this paper, for biliary tract cancer (BTC), therapies that target several regulators of cancer cell growth, including isocitrate dehydrogenase 1 (IDH1), fibroblast growth factor receptor 2 (FGFR2) fusion, proto-oncogene B-Raf (BRAF), and human epidermal growth factor receptor 2 (HER2) alterations, are reviewed. For pancreatic ductal adenocarcinoma (PDAC), therapies for Kirsten rat sarcoma virus (KRAS) gene mutation G12C, neuregulin (NRG)1, and breast cancer type 1 and 2 susceptibility (BRCA1/2), gene alterations are summarized. On the other hand, precision medicine targets were not established for hepatocellular carcinoma (HCC), although telomerase reverse transcriptase (TERT), tumor protein P53 (TP53), and Wnt/β catenin signaling alterations have been recognized as HCC driver oncogenes. Tumor-agnostic therapies for microsatellite instability-high (MSI-H) and neurotropic tyrosine receptor kinase (NTRK) fusion cancers effectively treat biliary and pancreatic cancers. Precision medicine methods developed using NGS of circulating tumor DNA (ctDNA) and utilizing a liquid biopsy technique are discussed.
近年来，采用综合基因组分析（CGP）和下一代测序（NGS）的肿瘤非特异性精准医学取得了进展。本综述聚焦于晚期不可切除肝胆胰癌的精准医学。在本文中，针对胆管癌（BTC），综述了靶向几种癌细胞生长调节因子的疗法，包括异柠檬酸脱氢酶1（IDH1）、成纤维细胞生长因子受体2（FGFR2）融合、原癌基因B-Raf（BRAF）和人表皮生长因子受体2（HER2）改变。对于胰腺导管腺癌（PDAC），总结了针对 Kirsten 大鼠肉瘤病毒（KRAS）基因突变G12C、神经调节蛋白（NRG）1以及乳腺癌1型和2型易感基因（BRCA1/2）改变的疗法。另一方面，尽管端粒酶逆转录酶（TERT）、肿瘤蛋白P53（TP53）和Wnt/β连环蛋白信号改变已被确认为肝细胞癌（HCC）的驱动癌基因，但尚未确立HCC的精准医学靶点。针对微卫星高度不稳定（MSI-H）和嗜神经酪氨酸受体激酶（NTRK）融合癌的肿瘤非特异性疗法可有效治疗胆管癌和胰腺癌。还讨论了利用循环肿瘤DNA（ctDNA）的NGS和液体活检技术开发的精准医学方法。
