Precision Medicine in Cholangiocarcinoma: Past, Present, and Future
Cholangiocarcinoma (CCA), or biliary tract cancer, has a poor prognosis. The median survival time among patients with CCA is under 2 years from diagnosis, and the global 5-year survival rate is only 10%. First-line therapy with chemotherapeutic agents, gemcitabine plus cisplatin, has traditionally b...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/12/6/829 |
| _version_ | 1797485245802479616 |
|---|---|
| author | Chi-Yuan Cheng Chiao-Ping Chen Chiao-En Wu |
| author_facet | Chi-Yuan Cheng Chiao-Ping Chen Chiao-En Wu |
| author_sort | Chi-Yuan Cheng |
| collection | DOAJ |
| description | Cholangiocarcinoma (CCA), or biliary tract cancer, has a poor prognosis. The median survival time among patients with CCA is under 2 years from diagnosis, and the global 5-year survival rate is only 10%. First-line therapy with chemotherapeutic agents, gemcitabine plus cisplatin, has traditionally been used to treat unresectable advanced CCA. In recent years, precision medicine has become a mainstream cancer treatment due to innovative next-generation sequencing technology. Several genetic alterations, including mutations, gene fusions, and copy number variations, have been found in CCA. In this review, we summarized the current understanding of genetic profiling in CCA and targeted therapy in CCA. Owing to the high heterogeneity of CCA, tumor microenvironmental factors, and the complexity of tumor biology, only pemigatinib, infigratinib, ivosidenib, larotrbctinib, and entrectinib are currently approved for the treatment of CCA patients with fibroblast growth factor receptor 2 gene (FGFR2) fusion, isocitrate dehydrogenase gene (IDH1) mutation, and neurotrophin receptor tyrosine kinase gene (NRTK) fusion, respectively. Additional targeted therapies, including other FGFR2 inhibitors, PI3K/AKT/mTOR inhibitors, and BRAF-directed targeted therapy, have been discussed for the management of CCA, and immune checkpoint inhibitors, particularly pembrolizumab, can be administered to patients with high microsatellite instability tumors. There is a further need for improvement in precision medicine therapies in the treatment of CCA and discuss the approved and potential targeted therapies for CCA. |
| first_indexed | 2024-03-09T23:16:02Z |
| format | Article |
| id | doaj.art-d3fdb1e15d1c46fea9c9866e6125b143 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T23:16:02Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-d3fdb1e15d1c46fea9c9866e6125b1432023-11-23T17:36:08ZengMDPI AGLife2075-17292022-06-0112682910.3390/life12060829Precision Medicine in Cholangiocarcinoma: Past, Present, and FutureChi-Yuan Cheng0Chiao-Ping Chen1Chiao-En Wu2Department of Pharmacy, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, TaiwanDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, TaiwanDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, TaiwanCholangiocarcinoma (CCA), or biliary tract cancer, has a poor prognosis. The median survival time among patients with CCA is under 2 years from diagnosis, and the global 5-year survival rate is only 10%. First-line therapy with chemotherapeutic agents, gemcitabine plus cisplatin, has traditionally been used to treat unresectable advanced CCA. In recent years, precision medicine has become a mainstream cancer treatment due to innovative next-generation sequencing technology. Several genetic alterations, including mutations, gene fusions, and copy number variations, have been found in CCA. In this review, we summarized the current understanding of genetic profiling in CCA and targeted therapy in CCA. Owing to the high heterogeneity of CCA, tumor microenvironmental factors, and the complexity of tumor biology, only pemigatinib, infigratinib, ivosidenib, larotrbctinib, and entrectinib are currently approved for the treatment of CCA patients with fibroblast growth factor receptor 2 gene (FGFR2) fusion, isocitrate dehydrogenase gene (IDH1) mutation, and neurotrophin receptor tyrosine kinase gene (NRTK) fusion, respectively. Additional targeted therapies, including other FGFR2 inhibitors, PI3K/AKT/mTOR inhibitors, and BRAF-directed targeted therapy, have been discussed for the management of CCA, and immune checkpoint inhibitors, particularly pembrolizumab, can be administered to patients with high microsatellite instability tumors. There is a further need for improvement in precision medicine therapies in the treatment of CCA and discuss the approved and potential targeted therapies for CCA.https://www.mdpi.com/2075-1729/12/6/829cholangiocarcinoma (CCA)targeted therapyNTRKIDH1FGFR2BRAF |
| spellingShingle | Chi-Yuan Cheng Chiao-Ping Chen Chiao-En Wu Precision Medicine in Cholangiocarcinoma: Past, Present, and Future Life cholangiocarcinoma (CCA) targeted therapy NTRK IDH1 FGFR2 BRAF |
| title | Precision Medicine in Cholangiocarcinoma: Past, Present, and Future |
| title_full | Precision Medicine in Cholangiocarcinoma: Past, Present, and Future |
| title_fullStr | Precision Medicine in Cholangiocarcinoma: Past, Present, and Future |
| title_full_unstemmed | Precision Medicine in Cholangiocarcinoma: Past, Present, and Future |
| title_short | Precision Medicine in Cholangiocarcinoma: Past, Present, and Future |
| title_sort | precision medicine in cholangiocarcinoma past present and future |
| topic | cholangiocarcinoma (CCA) targeted therapy NTRK IDH1 FGFR2 BRAF |
| url | https://www.mdpi.com/2075-1729/12/6/829 |
| work_keys_str_mv | AT chiyuancheng precisionmedicineincholangiocarcinomapastpresentandfuture AT chiaopingchen precisionmedicineincholangiocarcinomapastpresentandfuture AT chiaoenwu precisionmedicineincholangiocarcinomapastpresentandfuture |