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ATM Inhibitor Suppresses Gemcitabine-Resistant BTC Growth in a Polymerase θ Deficiency-Dependent Manner
Open AccessReview

Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials

1
National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan
2
Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
3
Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung 807, Taiwan
4
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
5
Department of Surgery, National Cheng Kung University Hospital, Tainan 704, Taiwan
6
Department of General Surgery and Liver Research Center, Chang Gung Memorial Hospital, Linkou Branch, Chang Gung University, Taoyuan 333, Taiwan
7
Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 112, Taiwan
8
School of Medicine, National Yang Ming University, Taipei 112, Taiwan
*
Authors to whom correspondence should be addressed.
Biomolecules 2021, 11(1), 97; https://doi.org/10.3390/biom11010097
Received: 27 October 2020 / Revised: 15 December 2020 / Accepted: 10 January 2021 / Published: 13 January 2021
Biliary tract cancer (BTC) compromises a heterogenous group of tumors with poor prognoses. Curative surgery remains the first choice for localized disease; however, most BTC patients have had unresectable or metastatic disease. The gold standard therapy for these patients is chemotherapy with gemcitabine and cisplatin. There are no consensus guidelines for standard treatment in a second-line setting, although the data of the ABC-06 trial showed a slight survival benefit from oxaliplatin and 5-fluorouracil combination chemotherapy. Recent progress in comprehensive genomic profiling for advanced BTC (ABTC) has helped to clarify tumorigenesis and facilitate the coming era of precision medicine. Generally, targeted agents fail to show significant clinical benefits in unselected populations. Only fibroblast growth factor receptor 2 (FGFR2) fusion and isocitrate dehydrogenase (IDH)- and BRAF mutation-enriched populations have survival benefits from the corresponding inhibitors. Several interesting targeted agents for monotherapies or combination therapies with other compounds are currently ongoing or recruiting. Here, we review the published data from clinical trials of second-line therapies after the failure of gemcitabine-based chemotherapy in ABTC. The results were stratified by different genetic alternations, as well as by chemotherapy, targeted therapy and immunotherapy. View Full-Text
Keywords: biliary tract cancer; next-line therapies; clinical trials biliary tract cancer; next-line therapies; clinical trials
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MDPI and ACS Style

Chiang, N.-J.; Chen, L.-T.; Shan, Y.-S.; Yeh, C.-N.; Chen, M.-H. Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials. Biomolecules 2021, 11, 97. https://doi.org/10.3390/biom11010097

AMA Style

Chiang N-J, Chen L-T, Shan Y-S, Yeh C-N, Chen M-H. Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials. Biomolecules. 2021; 11(1):97. https://doi.org/10.3390/biom11010097

Chicago/Turabian Style

Chiang, Nai-Jung; Chen, Li-Tzong; Shan, Yan-Shen; Yeh, Chun-Nan; Chen, Ming-Huang. 2021. "Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials" Biomolecules 11, no. 1: 97. https://doi.org/10.3390/biom11010097

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