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Targeted therapy for capillary-venous malformations

Signal Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： Lola Zerbib Sophia Ladraa Antoine Fraissenon Charles Bayard Marina Firpion Quitterie Venot Sanela Protic Clément Hoguin Amandine thomas Sylvie Fraitag Jean-Paul Duong Sophie Kaltenbach Estelle Balducci Coline Lefevre Patrick Villarese Vahid Asnafi Christine Broissand Nicolas Goudin Ivan Nemazanyy Gwennhael Autret Bertrand Tavitian Christophe Legendre Nadia Arzouk Veronique Minard-Colin Caroline Chopinet Michael Dussiot Denise MAdams Tristan Mirault Laurent Guibaud Paul Isenring Guillaume Canaud UniversitéParis Cité ParisFrance INSERM U1151 Institut Necker-Enfants MaladesParisFrance Service d’Imagerie Pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS UMR 5220 Villeurbanne 69100France Service de Radiologie Mère-Enfant Hôpital NordSaint EtienneFrance Service d’Anatomie pathologique Hôpital Necker-Enfants MaladesAP-HPParisFrance Laboratoire d’Oncohématologie Hôpital Necker-Enfants MaladesAP-HPParisFrance Pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance Necker Bio-Image Analysis INSERM US24/CNRS UMS 3633ParisFrance Platform for Metabolic Analyses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance Plateforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance Service de Néphrologie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance Service de Transplantation Hôpital La PitiéSalpétrièreAP-HPParisFrance Department of Pediatric and Adolescent Oncology INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance Service de Physiologie&Explorations Fonctionnelles Cardiovasculaires CHU de LilleLille 59000France INSERM U1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance Division of Oncology Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA Service de Médecine Vasculaire hôpital Européen Georges-PompidouParisFrance Nephrology Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada Unitéde médecine translationnelle et thérapies ciblées Hôpital Necker-Enfants MaladesAP-HPParisFrance CNRS UMR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or tek,an endothelial transmembrane receptor signaling through *** malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening *** authorized medical treatment exists for patients with venous ***,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient *** showed that these malformations only partially signal through AKT *** compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse *** demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging *** these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or tek(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous *** assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each *** demonstrated improvement in all 25 *** malformations previously considered intractable were reduced and clinical symptoms were *** showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and tek malformations respectively,over 6 months on *** conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or tek-related capillary venous malformations.

关键词： PIK3CA malformations venous

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Nanocarrier drug resistant tumor interactions: novel approaches to fight drug resistance in cancer

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Cancer Drug Resistance 2021年第2期4卷 264-297页

作者： Aleksandra Benko David Medina-Cruz Ada Vernet-Crua Catherine P.O'Connell MałgorzataŚwiętek Hamed Barabadi Muthupandian Saravanan thomas J.Webster AGH University of Science and Technology Faculty of Materials Science and CeramicsKrakow 30059Poland Department of Chemical Engineering Northeastern UniversityBostonMA 02115USA Institute of Macromolecular Chemistry Czech Academy of SciencesPrague 16206Czech Republic Department of Pharmaceutical Biotechnology School of PharmacyShahid Beheshti University of Medical SciencesTehran 19919-53381Iran Department of Medical Microbiology and Immunology Division of Biomedical SciencesSchool of MedicineCollege of Health SciencesMekelle UniversityMekelle 231Ethiopia.

Cancer is one of the biggest healthcare concerns in our century,a disease whose treatment has become even more difficult following reports of drug-resistant *** this happens,chemotherapy treatments fail or decrease in efficiency,leading to catastrophic consequences to the *** discovery,along with the fact that drug resistance limits the efficacy of current treatments,has led to a new wave of discovery for new methods of *** use of nanomedicine has been widely studied in current years as a way to effectively fight drug resistance in *** in the area of cancer nanotechnology over the past decades has led to tremendous advancement in the synthesis of tailored nanoparticles with targeting ligands that can successfully attach to chemotherapy-resistant cancer by preferentially accumulating within the tumor region through means of active and passive ***,these approaches can reduce the off-target accumulation of their payload and lead to reduced cytotoxicity and better *** review explores some categories of nanocarriers that have been used in the treatment of drug-resistant cancers,including polymeric,viral,lipid-based,metal-based,carbon-based,and magnetic nanocarriers,opening the door for an exciting field of discovery that holds tremendous promise in the treatment of these tumors.

关键词： Drug-resistance cancer nanotechnology nanocarriers drug delivery

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