RESUMO
Researchers in the adoptive T-cell therapy field are continuing to refine the ways in which the specificity of these immune cells can be redirected toward tumors. They've found that selecting the most persistent, proliferative T cells-and genetically manipulating only these defined subsets-ensures a potent therapeutic product that's effective even at minuscule doses.
Assuntos
Imunoterapia Adotiva , Neoplasias/imunologia , Neoplasias/terapia , Linfócitos T/imunologia , Terapia Baseada em Transplante de Células e Tecidos , Terapia Genética , Humanos , Imunoterapia Adotiva/métodos , Linfócitos T/metabolismoRESUMO
Although dendritic cells are abundant in ovarian tumors, scientists have been puzzled that these cells aren't immunostimulatory. New research reveals a role for the protein SATB1, which is transiently required during ovarian-associated dendritic cell maturation-its unremitting expression in these cells drives them to acquire an inflammatory, immunosuppressive phenotype.
Assuntos
Neoplasias Ovarianas/imunologia , Evasão Tumoral/imunologia , Células Dendríticas/metabolismo , Feminino , Humanos , MicroRNAs/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismoRESUMO
A comprehensive analysis of 1,122 diffuse glioma samples from The Cancer Genome Atlas has revealed two new subtypes of this common brain cancer, with molecular and clinical features that diverge from the norm. The study findings also support the use of DNA methylation profiles to improve glioma classification and treatment.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioma/diagnóstico , Glioma/genética , Isocitrato Desidrogenase/genética , Mutação , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Glioma/tratamento farmacológico , Glioma/mortalidade , HumanosAssuntos
Alphapapillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Vacinação , Feminino , Humanos , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/prevenção & controleRESUMO
Chemists at The Scripps Research Institute in La Jolla, CA, and Pfizer's La Jolla Laboratories have devised a new way to rapidly synthesize strained-ring structures, which are increasingly favored to optimize potential drugs. With this method, strain-release amination, Pfizer researchers were able to produce sufficient quantities of a particular structure they needed to evaluate a promising cancer drug candidate.
Assuntos
Descoberta de Drogas , Descoberta de Drogas/métodos , Descoberta de Drogas/normas , HumanosAssuntos
Tumores Neuroendócrinos/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Humanos , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Resultado do TratamentoAssuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Receptores Proteína Tirosina Quinases/metabolismo , Quinase do Linfoma Anaplásico , Antineoplásicos/farmacologia , Substituição de Medicamentos , Humanos , Inibidores de Proteínas Quinases/farmacologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/genética , Resultado do TratamentoRESUMO
The FDA has approved talimogene laherparepvec, or T-VEC, to treat surgically unresectable skin and lymph node lesions in patients with advanced melanoma. T-VEC is the first oncolytic viral therapy to gain regulatory endorsement, based on data from the OPTiM study.
Assuntos
Melanoma/terapia , Vírus Oncolíticos/fisiologia , Neoplasias Cutâneas/terapia , Anticorpos Monoclonais/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Quimioterapia Combinada , Humanos , Ipilimumab , Melanoma/imunologia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/imunologia , Neoplasias Cutâneas/imunologia , Resultado do TratamentoRESUMO
Novartis scientists have generated the PDX Encyclopedia, which contains over 1,000 patient-derived tumor xenograft models spanning a range of common solid cancers. They'll use this collection for in vivo drug screens designed to mimic human clinical trials, which they hope improves candidate therapy profiling.
Assuntos
Neoplasias/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Neoplasias/genética , Modelagem Computacional Específica para o Paciente , Medicina de PrecisãoRESUMO
In the last few weeks, the FDA approved three new therapies for multiple myeloma: ixazomib, the first oral proteasome inhibitor; and daratumumab and elotuzumab, two monoclonal antibodies that target CD38 and SLAMF7, respectively.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Compostos de Boro/administração & dosagem , Glicina/análogos & derivados , Mieloma Múltiplo/tratamento farmacológico , ADP-Ribosil Ciclase 1/metabolismo , Administração Oral , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Compostos de Boro/farmacologia , Ensaios Clínicos Fase III como Assunto , Glicina/administração & dosagem , Glicina/farmacologia , Humanos , Glicoproteínas de Membrana/metabolismo , Mieloma Múltiplo/metabolismo , Resultado do TratamentoRESUMO
A new NCI initiative aims to accrue and molecularly profile as many as 300 cases of exceptional responses to cancer therapies, both targeted and standard. Researchers hope this exercise will yield new hypotheses to be tested in genomically driven clinical trials.
Assuntos
Neoplasias/tratamento farmacológico , Medicina de Precisão , Humanos , Resultado do TratamentoRESUMO
DNA damage induces cell cycle arrest to provide time for repair and enhance cell survival. The Chk1 inhibitor 7-hydroxystaurosporine (UCN-01) can overcome both S and G(2) arrest and drive cells through a lethal mitosis. S-phase arrest induced by the topoisomerase I inhibitor SN38 results from activation of Chk1 and degradation of Cdc25A phosphatase that occurs independent of p53 status. However, p53-mediated induction of p21(waf1) and repression of cyclin B prevent abrogation of S and G(2) arrest, respectively. Surprisingly, incubation of MCF10A immortalized breast cells with UCN-01 fails to elevate Cdc25A protein due to p53-mediated inhibition of Cdc25A transcription. Suppression of p21(waf1) in MCF10A cells overcame this transcriptional inhibition, and the S-phase-arrested cells became sensitive to UCN-01, although they now arrested in G(2) as cyclin B expression remained suppressed. We also compared the response of p53 wild-type tumors to the combination of SN38 and UCN-01. In CAKI-1, U87MG, and SUM102, SN38 induced p21(waf1) and the cells were resistant to UCN-01. In contrast, HCT116 and MCF7 cells had markedly attenuated induction of p21(waf1) and failed to repress cyclin B. Accordingly, these cells were susceptible to UCN-01-mediated abrogation of both S and G(2) arrest. SN38 induced expression of another p53-inducible gene, 14-3-3sigma, suggesting selective dysregulation of p53 response genes. In summary, several cell lines commonly considered wild-type for p53 appear to have defects in expression of selected p53 response genes following DNA damage, and this makes them sensitive to the combination of DNA damage plus Chk1 inhibitor.