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Paradigm shift of chemotherapy and systemic treatment for biliary tract cancer

World Journal of Gastrointestinal Oncology 2023年第6期15卷 959-972页

作者： Wattana Leowattana Tawithep Leowattana Pathomthep Leowattana Department of Clinical Tropical Medicine Faculty of Tropical MedicineMahidol UniversityRachatawee 10400BangkokThailand Department of Medicine Faculty of MedicineSrinakharinwirot UniversityWattana 10110BangkokThailand

Biliary tract cancers(BTC)are frequently identified at late stages and have a poor prognosis due to limited systemic treatment *** more than a decade,the combination of gemcitabine and cis-platin has served as the first-line standard *** are few choices for second-line *** treatment with fibroblast growth factor receptor 2 inhibitors,neurotrophic tyrosine receptor kinase inhibitors,and isocitrate dehydrogenase 1 inhibitors has had important *** checkpoint inhibitors(ICI)such as pembrolizumab are only used in first-line treatment for microsatellite instability high *** TOPAZ-1 trial's outcome is encouraging,and there are several trials underway that might soon put targeted treatment and ICI combos into first-line *** targets and agents for existing goals are being studied,which may represent a paradigm shift in BTC *** to a scarcity of targetable mutations and the higher toxicity profile of the current medications,the new category of drugs may occupy a significant role in BTC therapies.

关键词： Biliary tract cancers Gemcitabine and cisplatin combination Fibroblast growth factor receptor 2 inhibitors Isocitrate dehydrogenase 1 inhibitors Neurotrophic tyrosine receptor kinase gene fusion inhibitors Immune checkpoint inhibitors microsatellite instability high Infrigatinib Pemigatinib

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Immunotherapy in biliary tract cancers:Current evidence and future perspectives

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World Journal of Gastrointestinal Oncology 2022年第8期14卷 1446-1455页

作者： Pedro Luiz Serrano Uson Junior Raphael LC Araujo Center for Personalized Medicine Hospital Israelita Albert EinsteinSão Paulo 05652-900Brazil Department of Surgery Universidade Federal de São PauloSão Paulo 04039-002Brazil Department of Oncology Hospital Israelita Albert EinsteinSão Paulo 05652-900Brazil

Bile duct tumors are comprised of tumors that originate from both intrahepatic and extrahepatic bile ducts and gallbladder *** are aggressive tumors and chemotherapy is still the main treatment for advanced-stage disease and most of these cases have a poor overall *** are aimed at treatments with better outcomes and less toxicity which makes immunotherapy an area of significant *** Food and Drug Administration approvals of immune checkpoint inhibitors(ICI)for agnostic tumors based on biomarkers such as microsatellite instability-high and tumor mutation burden-high are important steps in the treatment of patients with advanced bile duct *** limited responses with isolated checkpoint inhibitors in later lines of systemic treatment in advanced disease,drug combination strategies have been demonstrating encouraging results to enhance ICI efficacy.

关键词： Biliary tract cancer Cholangiocarcinoma Anti-programmed cell death protein-1 Anti-programmed death ligand-1 microsatellite instability high Tumor mutational burden high

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Tumor recurrence after pathological complete response in locally advanced gastric cancer after neoadjuvant therapy:Two case reports

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世界临床病例杂志 2023年第27期11卷 6483-6490页

作者： Yu Xing Zi-Li Zhang Zhi-Ying Ding Wei-Liang Song Tong Li Department of Surgery The Third Central Clinical College of Tianjin Medical UniversityTianjin 300170China Department of Surgery The Third Central Hospital of TianjinTianjin 300170China Department of Surgery Tianjin Institute of Hepatobiliary DiseaseTianjin 300170China

BACKGROUND The pathological complete response(ypCR)rate following neoadjuvant chemotherapy for advanced gastric cancer remains low and lacks a universally accepted treatment *** has achieved breakthrough *** SUMMARY We report two female patients with gastric cancer defined as clinical stage *** of mismatch repair protein showed mismatch repair function defect,and perioperative treatment with programmed death protein 1 inhibitor combined with S-1+oxaliplatin achieved ***,the patients underwent clinical observation after surgery but developed different degrees of metastasis at~6 mo after *** PD-1 inhibitor combined with chemotherapy provides a more strategic choice for comprehensive perioperative treatment of gastric cancer.

关键词： Programmed death protein 1 SOX Pathological complete response microsatellite instability high Mismatch repair function defect Case report

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The tumor microenvironment of pancreatic adenocarcinoma and immune checkpoint inhibitor resistance: a perplex relationship

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Cancer Drug Resistance 2020年第4期3卷 699-709页

作者： Irem Sahin Sevda Turen Pranav Santapuram Ibrahim Halil Sahin Baskent University School of Medicine Department of Medicine AnkaraAnkara 06810Turkey TC Istanbul Kültür University Faculty of Health SciencesDepartment of NursingIstanbul 34158Turkey Emory University School of Medicine Department of MedicineAtlantaGA 30322USA Moffitt Cancer Center Department of Gastrointestinal OncologyTampaFL 33612USA

Pancreatic cancer is one of the most aggressive cancers with a high mortality rate even among patients with early-stage *** recent studies with novel therapeutic approaches have led to modest improvement in survival outcomes,limited progress is achieved for the use of immunotherapeutics in this challenging *** checkpoint inhibitors,thus far,single-agent or in combination,have not yielded significant improvement in survival outcomes except in mismatch repair-deficient pancreatic *** tumor microenvironment of pancreatic cancer has been considered as an attractive target for over a decade based on preclinical studies that suggested it may adversely affect drug delivery and antitumor *** this review article,we elaborate on the biology of pancreatic cancer microenvironment,its highly complicated interaction with cancer cells,and the immune *** also discuss plausible explanations that led to the failure of immune checkpoint inhibitors as therapeutic agents and the potential impacts of pancreatic cancer stroma on these negative studies.

关键词： Pancreatic adenocarcinoma durvalumab nivolumab ipilimumab pembrolizumab immune checkpoint inhibitors immunotherapy resistance mismatch repair deficient microsatellite instability high microsatellite stable tumor-associated macrophages myeloid-derived suppressor cells T regs T cells

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