Current Opinion in Molecular Therapeutics最新文献

Alphavirus-based vaccines. Alphavirus-based疫苗。

Current Opinion in Molecular Therapeutics Pub Date : 2020-12-01 DOI: 10.1007/978-3-030-51927-8_11

K. Lundstrom

引用次数: 0

Pharmacogenetics of small-molecule tyrosine kinase inhibitors: Optimizing the magic bullet. 小分子酪氨酸激酶抑制剂的药物遗传学:优化灵丹妙药。

Current Opinion in Molecular Therapeutics Pub Date : 2010-12-01

Jan Pander, Henk Jan Guchelaar, Hans Gelderblom

{"title":"Pharmacogenetics of small-molecule tyrosine kinase inhibitors: Optimizing the magic bullet.","authors":"Jan Pander, Henk Jan Guchelaar, Hans Gelderblom","doi":"","DOIUrl":"","url":null,"abstract":"Cancer treatment has undergone revolutionary changes during the past decade, as a result of the introduction of tyrosine kinase inhibitors (TKIs) that selectively inhibit growth factor pathways critical for tumor growth. Unexpected toxicity profiles and disappointing response rates to these 'magic bullets' have prompted research to identify markers that can predict toxicity or response to such agents. This review discusses the results of pharmacogenetic studies that have used germline DNA to assess the effects of various polymorphisms on currently available small-molecule TKIs. In these studies, polymorphisms in the EGFR gene (ie, EGFR CA-repeat and -216G>T) have consistently been associated with response to the EGFR-blocking TKIs gefitinib and, to a lesser extent, erlotinib. In addition, results from studies investigating polymorphisms in drug transporting enzymes (ie, ABCB1 1236T>C, 2677G>T/A and 3435C>T, and ABCG2 421C>A) suggest such polymorphisms are relevant for the pharmacokinetics of the TKIs; however, some conflicting findings on these polymorphisms have been published. The clinical impact of polymorphisms in EGFR and in drug transporting enzymes needs to be evaluated and validated in order for these pharmacogenetic markers to be applied successfully to individualize treatment in the clinic.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 6","pages":"654-61"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecularly targeted therapies for colorectal cancer: Strategies for implementing translational research in clinical trials. 结直肠癌分子靶向治疗:在临床试验中实施转化研究的策略。

Current Opinion in Molecular Therapeutics Pub Date : 2010-12-01

Heinz Zwierzina, Alberto Bardelli, Fortunato Ciardiello, Manuela Gariboldi, Leif Håkansson, Diether Lambrechts, Guro E Lind, Judith Loeffler-Ragg, Hans Schmoll, Salvatore Siena, Josep Tabernero, Eric Van Cutsem

引用次数: 0

The emerging role of microRNAs in drug responses. microrna在药物反应中的新作用。

Current Opinion in Molecular Therapeutics Pub Date : 2010-12-01

Wei Zhang, M Eileen Dolan

引用次数: 0

Inflammation, stem cells and atherosclerosis genetics. 炎症，干细胞和动脉粥样硬化遗传学。

Current Opinion in Molecular Therapeutics Pub Date : 2010-12-01

Pascal J Goldschmidt-Clermont, David M Seo, Liyong Wang, Gary W Beecham, Zhao Jun Liu, Roberto I Vazquez-Padron, Chunming Dong, Joshua M Hare, Michael S Kapiloff, Nanette H Bishopric, Margaret Pericak-Vance, Jeffery M Vance, Omaida C Velazquez

{"title":"Inflammation, stem cells and atherosclerosis genetics.","authors":"Pascal J Goldschmidt-Clermont, David M Seo, Liyong Wang, Gary W Beecham, Zhao Jun Liu, Roberto I Vazquez-Padron, Chunming Dong, Joshua M Hare, Michael S Kapiloff, Nanette H Bishopric, Margaret Pericak-Vance, Jeffery M Vance, Omaida C Velazquez","doi":"","DOIUrl":"","url":null,"abstract":"Atherosclerosis and its associated complications remain the primary cause of death in humans. Aging is the main contributor to atherosclerosis, compared with any other risk factor, yet the specific manner in which age increases risk (the 'aging-risk' mechanism) remains elusive. A novel concept for atherosclerosis risk implicates a lack of endothelial progenitor cell (EPC)-dependent arterial repair in the development of the disease that is secondary to exhaustion of repair-competent EPCs. Molecular evidence derived from genetic techniques indicates atherosclerotic lesions may begin to form as arterial repair fails, rather than merely following arterial injury. Thus, chronic arterial injury may overwhelm the ability of EPCs to maintain arterial homeostasis, particularly when EPCs capable of arterial repair become exhausted. Recent studies have reported genes identified using non-biased approaches (ie, genetic linkage studies and genome-wide association studies) that are associated with susceptibility for atherosclerosis and related thromboembolic disorders; these genes may be implicated in the control of arterial wall inflammation and EPC-mediated tissue repair. Most of the genes identified by using non-biased genomic techniques are associated with inflammation, immune response and stem cells. This review focuses on new genetic data in the field of atherosclerosis and arterial homeostasis.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 6","pages":"712-23"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers. IPH-2101是一种全人源抗nk细胞抑制受体单克隆抗体，具有治疗血液病的潜力。

Current Opinion in Molecular Therapeutics Pub Date : 2010-12-01

Evren Alici

{"title":"IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers.","authors":"Evren Alici","doi":"","DOIUrl":"","url":null,"abstract":"NK-cell activity against tumor cells is regulated by a complex balance of inhibitory and activating signals, which are mediated by the binding of NK-cell receptors to activating and inhibitory ligands expressed on tumor cells. Thus, the disruption of the inhibitory cascade would shift the balance to activation. IPH-2101 (1-7F9), being developed by Innate Pharma, is a fully human IgG4 anti-killer immunoglobulin-like receptor (KIR) mAb for the treatment of hematological malignancies, such as acute myeloid leukemia (AML) and multiple myeloma (MM). In preclinical studies, IPH-2101 selectively bound to KIR2DL1, 2 and 3, and KIR2DS1 and 2, and exposure of KIR-transfected target cell lines to IPH-2101 led to an augmented NK-cell-mediated lysis. In phase I clinical trials in patients with AML and MM treated with IPH-2101, activation of NK cells was observed and IPH-2101 exhibited a good safety profile. At the time of publication, patients with MM had been recruited to phase II clinical trials to assess single-agent IPH-2101 or IPH-2101 in combination with lenalidomide. These and larger, randomized trials are warranted to clarify whether enhancing a patient's NK-cell activity by IPH-2101 will be a viable approach in the treatment of hematological malignancies.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 6","pages":"724-33"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rozrolimupab, symphobodies against rhesus D, for the potential prevention of hemolytic disease of the newborn and the treatment of idiopathic thrombocytopenic purpura. Rozrolimupab，抗D恒河猴的共生体，用于预防新生儿溶血性疾病和治疗特发性血小板减少性紫癜。

Current Opinion in Molecular Therapeutics Pub Date : 2010-12-01

Roberto Stasi

{"title":"Rozrolimupab, symphobodies against rhesus D, for the potential prevention of hemolytic disease of the newborn and the treatment of idiopathic thrombocytopenic purpura.","authors":"Roberto Stasi","doi":"","DOIUrl":"","url":null,"abstract":"Currently under codevelopment by Symphogen and Swedish Orphan Biovitrum, rozrolimupab is the first in a new class of recombinant polyclonal antibodies, known as symphobodies, produced using a proprietary technology from Symphogen. Rozrolimupab is being investigated for the prevention of hemolytic disease of the fetus and newborn (HDFN) and for the treatment of idiopathic thrombocytopenic purpura (ITP). Rozrolimupab comprises 25 genetically unique IgG1 antibodies, all of which are specific for the rhesus D (RhD) erythrocyte protein. In preclinical studies, rozrolimupab demonstrated binding to erythrocytes that was comparable with that of two plasma-derived anti-D Ig preparations. In a phase I clinical trial in healthy male volunteers, treatment with rozrolimupab was not associated with serious adverse events. In a phase II clinical trial of rozrolimupab in healthy, male, RhD-negative volunteers, rozrolimupab dose-dependently cleared RhD-positive erythrocytes from the circulation. Phase II clinical trials in ITP and HDFN are currently ongoing. Phase III clinical trials are necessary to establish the efficacy and safety profile of rozrolimupab compared with standard plasma-derived anti-D Ig preparations.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 6","pages":"734-40"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Small non-coding RNAs in disease development and host-pathogen interactions. 疾病发展和宿主-病原体相互作用中的小非编码rna。

Current Opinion in Molecular Therapeutics Pub Date : 2010-12-01

Mathieu Rederstorff, Alexander Hüttenhofer

引用次数: 0

Gene therapy: Have the risks associated with viral vectors been solved? 基因治疗:与病毒载体相关的风险已经解决了吗?

Current Opinion in Molecular Therapeutics Pub Date : 2010-12-01

J Todd Auman

引用次数: 0

Rindopepimut, a 14-mer injectable peptide vaccine against EGFRvIII for the potential treatment of glioblastoma multiforme. Rindopepimut，一种针对EGFRvIII的14分子注射肽疫苗，可用于多形性胶质母细胞瘤的潜在治疗。

Current Opinion in Molecular Therapeutics Pub Date : 2010-12-01

Catherine A Del Vecchio, Albert J Wong

{"title":"Rindopepimut, a 14-mer injectable peptide vaccine against EGFRvIII for the potential treatment of glioblastoma multiforme.","authors":"Catherine A Del Vecchio, Albert J Wong","doi":"","DOIUrl":"","url":null,"abstract":"Celldex Therapeutics is developing rindopepimut (CDX-110), a 14-mer injectable peptide vaccine for the potential treatment of glioblastoma multiforme (GBM). Rindopepimut specifically targets a novel junctional epitope of the EGFR deletion mutant EGFRvIII, which is a constitutively active receptor that is expressed in approximately 60 to 70% of patients with GBM. EGFRvIII expression is correlated with worse prognosis and reduced overall survival. Importantly, EGFRvIII is not expressed in normal brain tissue, making it an excellent therapeutic target. Preclinical studies demonstrated lasting tumor regression and increased survival times, as well as efficient generation of EGFRvIII-specific humoral and cellular immune responses, in animals expressing EGFRvIII and vaccinated with rindopepimut. Phase I and II clinical trials in patients with GBM demonstrated significantly increased median time to progression and overall survival time in those vaccinated with rindopepimut compared with matched historical controls. Only limited side effects have been observed in patients. Given these results, rindopepimut is an extremely promising therapy for patients with GBM. Phase I and II clinical trials in patients with GBM were ongoing at the time of publication. In the future, it may be beneficial to combine rindopepimut with other treatment modalities to further prolong survival.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 6","pages":"741-54"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0