Cholangiocarcinoma 2020: the next horizon in mechanisms and management

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2020, Volume and Issue: 17(9), P. 557 - 588

Published: June 30, 2020

Abstract Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point the tree. Their incidence is increasing globally, currently accounting for ~15% all primary liver cancers and ~3% gastrointestinal malignancies. The silent presentation these combined with their aggressive nature refractoriness to chemotherapy contribute alarming mortality, representing ~2% cancer-related deaths worldwide yearly. current diagnosis CCA by non-invasive approaches not accurate enough, histological confirmation necessary. Furthermore, high heterogeneity CCAs genomic, epigenetic molecular levels severely compromises efficacy available therapies. In past decade, efforts have been made understand complexity develop new diagnostic tools therapies might help improve patient outcomes. this expert Consensus Statement, which endorsed European Network Study Cholangiocarcinoma, we aim summarize critically discuss latest advances in CCA, mostly focusing on classification, cells origin, genetic abnormalities, alterations, biomarker discovery treatments. horizon next decade from 2020 onwards highlighted.

Language: Английский

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‘Off-the-shelf’ allogeneic CAR T cells: development and challenges

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(3), P. 185 - 199

Published: Jan. 3, 2020

Language: Английский

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Defining the Hallmarks of Metastasis

Cancer Research, Journal Year: 2019, Volume and Issue: 79(12), P. 3011 - 3027

Published: May 3, 2019

Abstract Metastasis is the primary cause of cancer morbidity and mortality. The process involves a complex interplay between intrinsic tumor cell properties as well interactions cells multiple microenvironments. outcome development nearby or distant discontiguous secondary mass. To successfully disseminate, metastatic acquire in addition to those necessary become neoplastic. Heterogeneity mechanisms involved, routes dissemination, redundancy molecular pathways that can be utilized, ability piggyback on actions surrounding stromal makes defining hallmarks metastasis extraordinarily challenging. Nonetheless, this review identifies four distinguishing features are required: motility invasion, modulate site local microenvironments, plasticity, colonize tissues. By these first principles metastasis, we provide means for focusing efforts aspects will improve patient outcomes.

Language: Английский

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The role of ubiquitination in tumorigenesis and targeted drug discovery

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Feb. 29, 2020

Ubiquitination, an important type of protein posttranslational modification (PTM), plays a crucial role in controlling substrate degradation and subsequently mediates the "quantity" "quality" various proteins, serving to ensure cell homeostasis guarantee life activities. The regulation ubiquitination is multifaceted works not only at transcriptional levels (phosphorylation, acetylation, methylation, etc.) but also level (activators or repressors). When regulatory mechanisms are aberrant, altered biological processes may induce serious human diseases, especially types cancer. In tumorigenesis, involve tumor metabolism, immunological microenvironment (TME), cancer stem (CSC) stemness so on. With regard some key proteins such as RagA, mTOR, PTEN, AKT, c-Myc P53 significantly regulates activity mTORC1, AMPK PTEN-AKT signaling pathways. addition, TLR, RLR STING-dependent pathways modulates TME. Moreover, core regulator triplets (Nanog, Oct4 Sox2) members Wnt Hippo-YAP participates maintenance CSC stemness. Based on components, including proteasome, E3 ligases, E1, E2 deubiquitinases (DUBs), many molecular targeted drugs have been developed combat Among them, small molecule inhibitors targeting bortezomib, carfilzomib, oprozomib ixazomib, achieved tangible success. MLN7243 MLN4924 (targeting E1 enzyme), Leucettamol A CC0651 nutlin MI-219 compounds G5 F6 DUB activity) shown potential preclinical treatment. this review, we summarize latest progress understanding substrates for their special functions metabolism regulation, TME modulation maintenance. therapeutic targets reviewed, effects drugs.

Language: Английский

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Cancer stem cells (CSCs) in cancer progression and therapy

Journal of Cellular Physiology, Journal Year: 2018, Volume and Issue: 234(6), P. 8381 - 8395

Published: Nov. 11, 2018

Abstract Cancer stem cells (CSCs) are self‐renewable cell types that identified in most of liquid and solid cancers contributed to tumor onset, expansion, resistance, recurrence, metastasis after therapy. CSCs from the expression surface markers, which is tumor‐type dependent. The transition between with cancer other non‐CSCs occurs cancers, possibly under control signals microenvironment (TME), including CSC niche. Cancer‐associated fibroblasts among influential for promoting both differentiation dedifferentiation toward attaining a CSC‐like phenotype. WNT/β‐catenin, transforming growth factor‐β, Hedgehog, Notch important maintaining self‐renewal CSCs. An effective therapeutic strategy relies on targeting remove possible chance relapse. There multiple ways target CSCs, immunotherapy, hormone therapy, (mi)siRNA delivery, gene knockout. Such approaches can be designed suppressing stemness, tumorigenic cues TME, extrinsic and/or intrinsic signaling, hypoxia or cells. Because sharing range characteristics normal stem/progenitor cells, must targeted based their unique markers preferential antigens.

Language: Английский

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Linking EMT programmes to normal and neoplastic epithelial stem cells

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(5), P. 325 - 338

Published: Feb. 5, 2021

Language: Английский

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Clinical and Therapeutic Implications of Cancer Stem Cells

New England Journal of Medicine, Journal Year: 2019, Volume and Issue: 380(23), P. 2237 - 2245

Published: June 5, 2019

Interview with Dr. Michael F. Clarke on clinical and therapeutic implications of cancer stem cells. (09:15)Download Cancers arise in tissues that can replicate self-renew. Like normal tissues, cancers replenish themselves, grow, metastasize because cells are similar to but seem respond less well environmental stop signals their niche. Therapy targets may be the next avenue treatment.

Language: Английский

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Protein arginine methylation: from enigmatic functions to therapeutic targeting

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(7), P. 509 - 530

Published: March 19, 2021

Language: Английский

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Cancer stem cells: A review from origin to therapeutic implications

Journal of Cellular Physiology, Journal Year: 2019, Volume and Issue: 235(2), P. 790 - 803

Published: July 8, 2019

Abstract Cancer stem cells (CSCs), also known as tumor‐initiating (TICs), are elucidated that can perpetuate themselves via autorestoration. These highly resistant to current therapeutic approaches and the main reason for cancer recurrence. Radiotherapy has made a lot of contributions treatment. However, despite continuous achievements, therapy resistance tumor recurrence still prevalent in most patients. This might be partly related existence CSCs. In present study, recent advances investigation different biological properties CSCs, such their origin, markers, characteristics, targeting have been reviewed. We focused our discussion on radioresistance adaptive responses CSCs extrinsic intrinsic influential factors. summary, we suggest prime target

Language: Английский

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Human germ cell tumours from a developmental perspective

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 19(9), P. 522 - 537

Published: Aug. 14, 2019

Language: Английский

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