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Novel biomarkers and the future of targeted therapies in cholangiocarcinoma:a narrative review

Hepatobiliary Surgery and Nutrition 2022年第2期11卷 253-266页

作者： Nishant Munugala Shishir K.Maithel Rachna T.Shroff Department of Medicine University of ArizonaTucsonAZUSA Division of Surgical Oncology Emory UniversityWinship Cancer InstituteAtlantaGAUSA Division of Hematology and Oncology Department of GI Medical OncologyUniversity of Arizona Cancer CenterTucsonAZUSA

Background and Objectives:Cholangiocarcinoma is a highly aggressive and heterogenous group of biliary malignancies arising from any site in the biliary tree,comprising 15%of all primary liver *** nature of the disease and nonspecific presentation leads to late diagnosis and ultimately poor outcomes for *** gemcitabine and cisplatin has been the standard of care for cholangiocarcinoma(CCA)since 2010,with a median overall survival of 11.7 *** five-year survival for CCA remains 5-10%,revealing a clear need for improved treatment ***:This targeted review highlights the role of next generation sequencing in CCA and the clinically relevant tumor biomarkers that have become the focus of therapeutic *** Content and Findings:These tumor biomarkers or actionable mutations hold the potential to enable earlier diagnosis,provide prognostic information,and guide treatment decisions for patients with ***,the FGFR2 fusion and IDH1 mutation have shown considerable promise in development of targeted *** trials with inhibitors targeting FGFR2 fusion and IDH1 mutation have created expectations that these drugs will soon enter clinical *** biomarkers including KRAS and B-raf protooncogenes,Her2/neu genes,and BRCA1 and 2 tumor-suppressor genes have also been touted as potential targets for future therapies,with early data showing promise for new drug ***:The discovery of these actionable mutations and identification of targeted therapies have challenged the notion of a“one-size fits all”for treatment of CCA,and generated optimism that these novel treatments will soon be available for patients with CCA.

关键词： Cholangiocarcinoma(CCA) targeted therapies IDH FGFR2 fusion tumor biomarkers

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Advances in radiotherapy and targeted therapies for rectal cancer

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World Journal of Gastroenterology 2014年第1期20卷 1-5页

作者： Alexandra Sermeus Wim Leonard Benedikt Engels Mark De Ridder UZ Brussel Vrije Universiteit BrusselDepartment of GastroenterologyB-1090 BrusselsBelgium UZ Brussel Vrije Universiteit BrusselDepartment of RadiotherapyB-1090 BrusselsBelgium

The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in *** stepwise implementation of intensitymodulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery,reducing treatment related *** addition,the administration of a simultaneous integrated boost offers excellent local control *** novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving ***,distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor *** expected benefit of target?ed therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals,hence hardly justifying rather modest improvements in patient *** the other hand,the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune *** N2 neutrophils and myeloid-derived suppressor cells(MDSC)emerge as useful clinical biomarkers of poor prognosis,while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical ***,integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.

关键词： Rectal cancer Image-guided radiotherapy Intensity-modulated radiotherapy Biomarkers targeted therapies Myeloid-derived suppressor cells

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Current concepts in ameloblastoma-targeted therapies in B-raf proto-oncogene serine/threonine kinase V600E mutation: Systematic review

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World Journal of Clinical Oncology 2020年第1期11卷 31-42页

作者： Rogelio González-González Sandra López-Verdín Jesús Lavalle-Carrasco Nelly Molina-Frechero Mario Isiordia-Espinoza Ramón G Carreón-Burciaga Ronell Bologna-Molina Department of Research School of DentistryUniversidad Juárez del Estado de DurangoDurango 34000Mexico Research Institute of Dentistry Health Science CenterUniversidad de GuadalajaraGuadalajara 4430Mexico Department of Health Care Xochimilco UnitUniversidad Autónoma Metropolitana XochimilcoMéxico 04960Mexico Department of Clinics Biomedical Sciences DivisionCentro Universitario de los AltosUniversidad de GuadalajaraTepetitlán de Morelos 47620Mexico Molecular Pathology Area School of DentistryUniversidad de la RepúblicaMontevideo 11600Uruguay

BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment *** signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell *** gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its *** therapies have been used as an alternative in the case of resistance or contraindications to conventional *** To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these *** An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO *** criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF *** were evaluated by two independent reviewers and retrieved for full-text *** EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible *** statistical analysis was *** Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this *** analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatom

关键词： Ameloblastoma B-raf proto-oncogene serine/threonine kinase B-raf protooncogene serine/threonine kinase V600E Additional mutations targeted therapies

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Senescence in chronic wounds and potential targeted therapies

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Burns & Trauma 2022年第1期10卷 742-756页

作者： Xuerong Wei Minxiong Li Zijun Zheng Jun Ma Yanbin Gao Lianglong Chen Yujie Peng Shengxiang Yu Lei Yang Department of Burns Nanfang HospitalSouthern Medical UniversityJingxi StreetBaiyun DistrictGuangzhou510515China Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai JiaoTong University School of Medicine639 Zhizaoju Road200011ShanghaiChina

Chronic wounds(*** wounds,pressure wounds,vascular ulcers,etc.)do not usually heal in a timely and orderly manner but rather last for years and may lead to irreversible adverse events,resulting in a substantial financial burden for patients and ***,a large amount of evidence has proven that cellular senescence has a crucial influence on chronic nonhealing *** a defensive mechanism,cell senescence is a manner of cell-cycle arrest with increased secretory phenotype to resist death,preventing cells from stress-induced damage in cancer and noncancer diseases.A growing amount of research has advanced the perception of cell senescence in various chronic wounds and focuses on pathological and physiological processes and therapies targeting senescent ***,previous reviews have failed to sum up novel understandings of senescence in chronic wounds and emerging strategies targeting ***,we discuss the characteristics and mechanisms of cellular senescence and the link between senescence and chronic wounds as well as some novel antisenescence strategies targeting other diseases that may be applied for chronic wounds.

关键词： Chronic wounds Senescence Senolytics targeted therapies Diabetic wound Pressure wound Vascular ulcer

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Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments

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World Journal of Stem Cells 2024年第5期16卷 604-614页

作者： Edoardo Agosti Marco Zeppieri Mattia Ghidoni Tamara Ius Alessandro Tel Marco Maria Fontanella Pier Paolo Panciani Division of Neurosurgery Department of Medical and Surgical SpecialtiesRadiological Sciences and Public HealthUniversity of BresciaBrescia 25123Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Neurosurgery Unit Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy Clinic of Maxillofacial Surgery Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and *** stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and *** studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular *** mechanisms can involve different cellular pathways,most of which have been recently reported in the *** progress,targeted therapeutic approaches lack consensus due to GSCs’high *** To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying *** A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,*** search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text *** them,201 were deemed eligible after excluding 168 for various *** temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma *** analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance *** molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette

关键词： Glioma stem cells Chemoresistance Radioresistance Molecular pathways targeted therapies Systematic review

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Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling

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Oncology Research 2024年第6期32卷 1119-1128页

作者： YUE ZHANG WENYU YANG XIAOWANG HAN YUE QIAO HAITAO WANG TING CHEN TIANYING LI WEN-BIN OU Department of Biopharmaceutics College of Life Sciences and MedicineZhejiang Provincial Key Laboratory of Silkworm Bioreactor and BiomedicineZhejiang Sci-Tech UniversityHangzhou310018China Department of Thoracic Surgery Zhejiang Provincial People’s HospitalHangzhou310014China

It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is still *** current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma(LUAD).Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies,and through analysis of The Cancer Genome Atlas(TCGA)*** HE4 overexpression was demonstrated in LUAD,but not in lung squamous cell carcinoma(LUSC),indicating that HE4 can serve as a biomarker to distinguish between LUAD and ***4 knockdown significantly inhibited cell growth,colony formation,wound healing,and invasion,and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK *** first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells,while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative ***,we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in *** findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.

关键词： Lung adenocarcinoma Human epididymis protein 4 Epidermal growth factor receptor Biomarker targeted therapies

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The Role of E3 Ligases in Macrophage-mediated Inflammation

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生物化学与生物物理进展 2024年第9期51卷 2037-2060页

作者： JIN Jia-Bei GE Yi-Dong JIN Xiao-Feng Zhejiang Key Laboratory of Pathophysiology Department of Biochemistry and Molecular BiologyHealth Science CenterNingbo UniversityNingbo 315211China

Macrophages,existed in almost all organs of the body,are responsible for detecting tissue injury,pathogens,playing a key role in host defense against a variety of invading pathogens triggering inflammatory *** evidence suggests that macrophage-mediated immune responses are efficiently regulated by the ubiquitination modification,which is responsible for normal immune ***,numerous studies indicates that the aberrant activation or inhibition of macrophage-mediated immune responses occurs in inflammation,mainly caused by dysregulated ubiquitination modification due to E3 ubiquitin ligases mutations or abnormal ***,E3 ubiquitin ligases,responsible for recognizing the substrates,are key enzymes in the ubiquitin proteasome system(UPS)composed of ubiquitin(Ub),ubiquitin-activating E1 enzymes,ubiquitin-conjugating E2 enzymes,E3 ubiquitin ligases,26S proteasome,and deubiquitinating ***,several E3 ubiquitin ligases are involved in the regulation of some common signal pathways in macrophage-mediated inflammation,including Toll-like receptors(TLRs),nucleotide-binding oligomerization domain(NOD)-like receptors(NLRs),RIG-I-like receptors(RLRs),C-type lectin receptors(CLRs)and the receptor for advanced glycation end products(RAGE).Herein,we summarized the physiological and pathological roles of E3 ligases in macrophage-mediated inflammation,as well as the inhibitors and agonists targeting E3 ligases in macrophage mediated inflammation,providing the new ideas for targeted therapies in macrophage-mediated inflammation caused aberrant function of E3 ligases.

关键词： E3 ligases macrophage NLRs/RLRs/TLRs targeted therapies

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Advancing the understanding and management of blastic plasmacytoid dendritic cell neoplasm:Insights from recent case studies

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World Journal of Clinical Cases 2024年第31期12卷 6441-6446页

作者： Yan Luo Li-Juan Wang Cheng-Long Wang Department of Stomatology The People's Hospital of Dadukou DistrictChongqing 400084China Department of Pathology The Chongqing Hospital of Traditional Chinese MedicineChongqing 400021China

We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic *** article enriches our understanding of BPDCN through detailed case reports showing the clinical,immunophenotypic,and histopathological features that are critical for diagnosing this *** cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment ***,we explore the implications of these findings for management strategies,emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving *** editorial underscores the importance of interdisciplinary approaches in managing BPDCN,pointing towards a future where precision medicine could significantly improve patient outcomes.

关键词： Blastic plasmacytoid dendritic cell neoplasm Immunophenotyping targeted therapies Haematologic malignancy Pathogenesis

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Cell-cell interactions and communication dynamics in lung fibrosis

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第2期2卷 63-71页

作者： Ting Xie Jiurong Liang Barry Stripp Paul W.Noble Division of Pulmonary and Critical Care Medicine Department of MedicineWomen’s Guild Lung InstituteCedars-Sinai Medical CenterLos AngelesCA 90048USA

Cell-cell interactions are essential components of coordinated cell function in lung *** diseases involve altered cell-cell interactions and communication between different cell types,as well as between subsets of cells of the same *** identification and understanding of intercellular signaling in lung fibrosis offer insights into the molecular mechanisms underlying these interactions and their implications in the development and progression of lung fibrosis.A comprehensive cell atlas of the human lung,established with the facilita-tion of single-cell RNA transcriptomic analysis,has enabled the inference of intercellular communications using ligand-receptor *** this review,we provide a comprehensive overview of the modified cell-cell commu-nications in lung *** highlight the intricate interactions among the major cell types within the lung and their contributions to *** insights presented in this review will contribute to a better understand-ing of the molecular mechanisms underlying lung fibrosis and may guide future research efforts in developing targeted therapies for this debilitating disease.

关键词： Cell–cell interaction Lung fibrosis Lung homeostasis targeted therapies

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Emerging therapies in gastrointestinal cancers

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World Journal of Gastroenterology 2006年第46期12卷 7440-7450页

作者： Jyoti Nautiyal Arun K Rishi Adhip PN Majumdar Karmanos Cancer Institute Detroit MI 48201United States Karmanos Cancer Institute Veterans Affairs Medical Center Departments of Internal Medicineand Wayne State University Detroit MI 48201 United States

Members of the receptor tyrosine kinase family, that include EGFR, ErbB-2/HER-2, ErbB-3/HER-3 and ErbB-4/ HER-4, are frequently implicated in experimental models of epithelial cell neoplasia as well as in human cancers. Therefore, interference with the activation of these growth factor receptors represents a promising strategy for de- velopment of novel and selective anticancer therapies. Indeed, a number of inhibitors that target either EGFR or HER-2, with the exception of a few that target both; have been developed for treatment of epithelial cancers. Since most solid tumors express different ErbB receptors and/or their ligands, identification of inhibitor(s), targeting multiple EGFR family members may provide a therapeutic benefit to a broader patient population. Here we describe the significance of an ErbB family of receptors in epithelial cancers, and summarize different available therapeutics targeting these receptors. It also emphasizes the need to develop pan-ErbB inhibitors and discusses EGF-Receptor Related Protein, a recently isolated negative regulator of EGFR as a potential pan-ErbB therapeutic for a wide vari- ety of epithelial cancers.

关键词： Gastrointestinal cancers Carcinogenesis targeted therapies Pan-ErbB family EGF-Receptor Related Protein

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