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1.
Lancet ; 395(10229): 1078-1088, 2020 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-32222192

RESUMO

The identification of molecular targets and the growing knowledge of their cellular functions have led to the development of small molecule inhibitors as a major therapeutic class for cancer treatment. Both multitargeted and highly selective kinase inhibitors are used for the treatment of advanced treatment-resistant cancers, and many have also achieved regulatory approval for early clinical settings as adjuvant therapies or as first-line options for recurrent or metastatic disease. Lessons learned from the development of these agents can accelerate the development of next-generation inhibitors to optimise the therapeutic index, overcome drug resistance, and establish combination therapies. The future of small molecule inhibitors is promising as there is the potential to investigate novel difficult-to-drug targets, to apply predictive non-clinical models to select promising drug candidates for human evaluation, and to use dynamic clinical trial interventions with liquid biopsies to deliver precision medicine.


Assuntos
Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular/tendências , Neoplasias/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Ensaios Clínicos como Assunto , Desenvolvimento de Medicamentos , Quimioterapia Combinada , Previsões , Humanos , Terapia de Alvo Molecular/métodos , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Inibidores de Proteínas Quinases/uso terapêutico
3.
World J Gastroenterol ; 25(38): 5773-5788, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31636471

RESUMO

Gastric cancer (GC) represents a leading cause of cancer related morbidity and mortality worldwide accounting for more than 1 million of newly diagnosed cases and thousands of deaths every year. In the last decade, the development of targeted therapies and the optimization of already available chemotherapeutic drugs has expanded the available treatment options for advanced GC and granted better survival expectations to the patients. At the same time, global efforts have been undertaken to investigate in detail the genomic and epigenomic heterogeneity of this disease, resulting in the identification of new specific and sensitive predictive and prognostic biomarkers and in innovative molecular classifications based on gene expression profiling. Nonetheless, several randomized studies aimed at exploring new innovative agents, such as immune checkpoint inhibitors, failed to demonstrate clinically meaningful survival advantages. Therefore, it is essential to further improve the molecular characterization of GC subgroups in order to provide researchers and medical oncologists with new tools for patients' selection and stratification in future clinical development programs and subsequent trials. The aim of the present manuscript is to provide a global overview of the recent molecular classifications from The Cancer Genome Atlas and the Asian Cancer Research Group and to present key promising developments in the field of immunotherapy and targeted therapies in metastatic GC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Medicina de Precisão/métodos , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Receptores Coestimuladores e Inibidores de Linfócitos T/antagonistas & inibidores , Humanos , Imunoterapia/tendências , Terapia de Alvo Molecular/tendências , Seleção de Pacientes , Medicina de Precisão/tendências , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do Tratamento
4.
World Neurosurg ; 131: 328-338, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31658576

RESUMO

Glioblastomas are the most common malignant brain tumor and despite extensive research have a dismal prognosis. This review focuses on the current treatment paradigms of glioblastoma and highlights current advances in surgical approaches, imaging techniques, molecular diagnostics, and translational efforts. Several promising clinical trials in immunotherapy and personalized medicine are discussed and the importance of quality of life in the patients and their caregivers both during active treatment and survivorship is also commented on.


Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/diagnóstico , Ensaios Clínicos como Assunto , Fracionamento da Dose de Radiação , Feminino , Previsões , Glioblastoma/diagnóstico , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Imagem por Ressonância Magnética/métodos , Imagem por Ressonância Magnética/tendências , Masculino , Terapia de Alvo Molecular/tendências , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/tendências , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/tendências , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Qualidade de Vida , Fatores de Risco
5.
Nat Rev Clin Oncol ; 16(12): 773-778, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31477881

RESUMO

For many years, oncology phase I trials have been referred to as 'toxicity trials' and have been believed to have low clinical utility other than that of establishing the adverse event profile of novel therapeutic agents. The traditional distinction of clinical trials into three phases has been challenged in the past few years by the introduction of targeted therapies and immunotherapies into the routine management of patients with cancer. This transformation has especially affected early phase trials, leading to the current situation in which response rates are increasingly reported from phase I trials. In this Perspectives, we highlight key elements of phase I trials and discuss how each one of them contributes to a new paradigm whereby preliminary measurements of the clinical benefit from a novel treatment can be obtained in current phase I trials, which can therefore be considered to have a therapeutic intent.


Assuntos
Ensaios Clínicos Fase I como Assunto , Neoplasias/terapia , Comportamento de Escolha , Ensaios Clínicos Fase I como Assunto/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Drogas em Investigação/efeitos adversos , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Imunoterapia/tendências , Oncologia/métodos , Oncologia/tendências , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Terapias em Estudo/métodos , Terapias em Estudo/tendências
6.
Med Sci (Paris) ; 35(8-9): 667-673, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31532379

RESUMO

Viruses are obligatory intracellular parasites that rely on a wide range of cellular factors to successfully accomplish their infectious cycle. Among those, micro (mi)RNAs have recently emerged as important modulators of viral infections. These small regulatory molecules act as repressors of gene expression. During infection, miRNAs can function by targeting either cellular or viral RNAs. In this review, we will recapitulate what has been reported to date on this interplay between cellular miRNAs and viruses and the effect on the infection. Furthermore, we will briefly discuss the possibilities of interfering with the infection through the modulation of this pathway to develop novel antiviral therapies.


Assuntos
Interações Hospedeiro-Patógeno/genética , MicroRNAs/fisiologia , Viroses/genética , Viroses/imunologia , Animais , Antivirais/uso terapêutico , Interações Hospedeiro-Patógeno/imunologia , Humanos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Viroses/terapia , Replicação Viral/genética , Vírus/genética , Vírus/imunologia
7.
Int J Mol Sci ; 20(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470642

RESUMO

The concept of leukemic stem cells (LSC) has been developed with the idea to explain the clonal hierarchies and architectures in leukemia, and the more or less curative anti-neoplastic effects of various targeted drugs. It is now widely accepted that curative therapies must have the potential to eliminate or completely suppress LSC, as only these cells can restore and propagate the malignancy for unlimited time periods. Since LSC represent a minor cell fraction in the leukemic clone, little is known about their properties and target expression profiles. Over the past few years, several cell-specific immunotherapy concepts have been developed, including new generations of cell-targeting antibodies, antibody-toxin conjugates, bispecific antibodies, and CAR-T cell-based strategies. Whereas such concepts have been translated and may improve outcomes of therapy in certain lymphoid neoplasms and a few other malignancies, only little is known about immunological targets that are clinically relevant and can be employed to establish such therapies in myeloid neoplasms. In the current article, we provide an overview of the immunologically relevant molecular targets expressed on LSC in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). In addition, we discuss the current status of antibody-based therapies in these malignancies, their mode of action, and successful examples from the field.


Assuntos
Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide/terapia , Células-Tronco Neoplásicas/efeitos dos fármacos , Doença Aguda , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Antígeno CTLA-4/metabolismo , Humanos , Imunoterapia/tendências , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mieloide/imunologia , Leucemia Mieloide/metabolismo , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/metabolismo
8.
Presse Med ; 48(7-8 Pt 1): 859-870, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447331

RESUMO

Non-follicular small cell lymphomas include several entities whose clinical and pathological descriptions have been refined in the last 20 years. MALT lymphoma, developed at the expense of lymphoid tissue associated with the mucosa, is usually localized to a given organ, but can also disseminate. Some patients with MALT lymphoma can be treated by eradicating the associated infectious agent, whereas local treatment should be preferred for other cases ; disseminated forms and relapsed patients are eligible for anti-CD20 antibodies associated with cytotoxic agents. Patients with mantle cell lymphoma have benefited from many advances, including the use of cytarabine and bendamustine, anti-CD20 antibodies, intensive treatments (autograft) and recently targeted therapy (ibrutinib, inhibitor or the Bruton tyrosine kinase). Patients with splenic nodal marginal zone lymphomas should be evaluated for different options, of which immunochemotherapy remains important. For all these entities, the implementation of treatments may be delayed by several years for certain groups of patients. Although considered as incurable, the prognosis of these pathologies has improved significantly and the majority of patients will be able to live for many years with often treatment-free intervals.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Fatores Etários , Idade de Início , Anticorpos Monoclonais/uso terapêutico , Diagnóstico Diferencial , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Linfoma de Zona Marginal Tipo Células B/classificação , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Linfoma de Zona Marginal Tipo Células B/terapia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Prognóstico , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/epidemiologia , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
9.
Presse Med ; 48(7-8 Pt 1): 807-815, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447332

RESUMO

Chronic lymphocytic leukemia is the most frequent adult leukemia. Eighty per cent of the patients are asymptomatic at diagnosis and 30% of the patients will be never treated. The diagnosis is based on the blood smear examination and immunophenotyping by flow cytometry of blood lymphocytes. The first line option is immunochemotherapy in 90% of the patients without genetic abnormalities associated with chemo resistance. The use of new compounds targeting different pathways is more frequent especially in relapsing patients and could be an alternative to the chemotherapy in the future. Asymptomatic patients with a stable disease assessed by the specialist can be followed by the general practitioner with a blood count and clinical examination every six months or once a year.


Assuntos
Leucemia Linfocítica Crônica de Células B , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Imunoterapia , Leucemia Linfocítica Crônica de Células B/classificação , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/terapia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Terapias em Estudo/métodos , Terapias em Estudo/tendências
10.
Presse Med ; 48(7-8 Pt 1): 832-841, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31444019

RESUMO

Lymphoplasmocytic lymphona with monoclonal lgM, rare. Median age at diagnosis 70 years old, frail population. Heterogenous clinic presentation. Molecular diagnosis with MYD88. Treatment required for symptomatic WM patients only. 1st line therapy: DRC. Input of targeted therapies (ibrutinib) for frail patients, maintenance effect.


Assuntos
Macroglobulinemia de Waldenstrom , Idade de Início , Idoso , Análise Mutacional de DNA/métodos , Idoso Fragilizado , Humanos , Técnicas de Diagnóstico Molecular/métodos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Fator 88 de Diferenciação Mieloide/genética , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/epidemiologia , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/terapia
11.
Crit Rev Oncol Hematol ; 141: 139-145, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31295667

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of diffuse large B-cell lymphoma. The frontline treatment with high-dose methotrexate based immunochemotherapy is not curative for the majority of patients. Gene expression profiling and next-generation sequencing have recently provided plethora of data shedding light on pathogenic mechanisms sustain PCNSL and identifying potential vulnerable mechanisms to be explored therapeutically. Here, we review established molecular drivers of PCNSL and targeted drugs that may change the current therapeutic paradigm.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Terapia de Alvo Molecular , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Terapias em Estudo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Metotrexato/administração & dosagem , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Terapias em Estudo/métodos , Terapias em Estudo/tendências
12.
J Cancer Res Clin Oncol ; 145(8): 1977-1986, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31309300

RESUMO

CONTEXT: Parathyroid carcinoma (PC) is a rare endocrine malignancy with no approved systemic therapies for unresectable locally invasive or distant metastatic disease. Understanding the molecular changes in advanced PC can provide better understanding of this disease and potentially help directing targeted therapy. OBJECTIVE: To evaluate tumor-specific genetic changes using next-generation sequencing (NGS) panels. DESIGN: All patients with advanced PC were tested for hot-spot panels using NGS panels including a 50-gene panel, a 409-gene panel if the standard 50-gene panel (Ion Torrent, Life Technology) was negative or a FoundationOne panel. SETTING: The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. PATIENTS OR OTHER PARTICIPANTS: 11 patients with advanced PC were selected to undergo molecular testing. MAIN OUTCOME MEASURE(S): Genetic profiles of advanced PC. RESULTS: Among the 11 patients, 4 patients had the 50-gene panel only, 6 had 409-gene panel after a negative 50-gene panel and 1 had FoundationOne. One patient who had 50-gene panel only also had his metastatic site (esophagus) of his tumor tested with FoundationOne. The most common mutations identified were in the PI3 K (PIK3CA, TSC1 and ATM) (4/11 patients) and TP53 (3/11) pathways. Genes not previously reported to be mutated in PC included: SDHA, TERT promoter and DICER1. Actionable mutations were found in 54% (6/11) of the patients. CONCLUSIONS: Mutational profiling using NGS panels in advanced PC has yielded important potentially targetable genetic alterations. Larger studies are needed to identify commonly mutated genes in advanced PC patients. Development of novel therapies targeting these cellular pathways should be considered.


Assuntos
Carcinoma/genética , Perfilação da Expressão Gênica , Técnicas de Diagnóstico Molecular/métodos , Monitorização Fisiológica/métodos , Neoplasias das Paratireoides/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma/terapia , Análise Mutacional de DNA/métodos , Progressão da Doença , Feminino , Seguimentos , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/tendências , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/terapia
13.
Autoimmun Rev ; 18(9): 102348, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31323365

RESUMO

Psychotic disorders are debilitating mental illnesses associated with abnormalities in various neurotransmitter systems. The development of disease-modifing therapies has been hampered by the mostly unknown etiologies and pathophysiologies. Autoantibodies against several neuronal antigens are responsible for autoimmune encephalitis. These autoantibodies disrupt neurotransmission within the brain, resulting in a wide range of psychiatric and neurologic manifestations, including psychosis. The overlap of symptoms of autoimmune encephalitis with psychotic disorders raised the question as to whether autoantibodies against a number of receptors, ion channel and associated proteins could ultimately be responsible for some forms of psychosis. Here we review our current knowledge, on antibody mediated autoimmunity in psychotic disorders, the different diagnostic methods and their limitations, as well as on varying therapeutic approaches targeting the immune system.


Assuntos
Autoimunidade/fisiologia , Testes Imunológicos/tendências , Imunoterapia/tendências , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/imunologia , Transtornos Psicóticos/terapia , Autoanticorpos/análise , Autoanticorpos/sangue , Autoanticorpos/imunologia , Encéfalo/fisiologia , Encefalite/diagnóstico , Encefalite/imunologia , Encefalite/terapia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Doença de Hashimoto/terapia , Humanos , Sistema Imunitário/fisiologia , Testes Imunológicos/métodos , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Neurônios/imunologia , Neurônios/patologia
15.
Immunol Med ; 42(1): 10-15, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31204894

RESUMO

Atopic dermatitis (AD) is caused by complex interactions between a variety of genetic and environmental factors that contribute to the maintenance of the chronic inflammatory skin condition. Most conventional treatments have been designed for the so-called 'average patient'. In recent years however, many previously unknown details pertaining to the mechanisms of the pathogenesis of AD have been elucidated, and novel treatments based on these pathological mechanisms or on subgroup classifications have been developed. Herein, how future treatment strategies for AD can be developed is described.


Assuntos
Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/etiologia , Terapia de Alvo Molecular/tendências , Animais , Anticorpos , Anticorpos Monoclonais/uso terapêutico , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Humanos , Imunoglobulina E/imunologia , Subunidade alfa de Receptor de Interleucina-4/imunologia , Proteínas de Filamentos Intermediários/genética , Camundongos , Mutação , Ácidos Nucleicos/uso terapêutico , Oligodesoxirribonucleotídeos/uso terapêutico , Fator de Transcrição STAT6 , beta-Defensinas
16.
Crit Rev Oncol Hematol ; 138: 38-43, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31092383

RESUMO

Neuroblastoma is the most common solid extracranial tumor in pediatrics and can regress spontaneously or grow and metastasize with resistance to multiple therapeutic approaches. The prognosis and approach to treatment depends on the tumor presentation and whether it expresses certain drivers such as MYCN, ALK, and TrkB. Expression or mutation of these genes and kinases correlates with high-risk and poor prognosis. Multiple therapeutic approaches are being used to target MYCN, ALK, and TrkB, as well as GD2, a surface antigen present on the surface of neuroblastoma tumor cells. This review discusses the nature of these targets and several current therapies for neuroblastoma. A focus is placed on recent therapeutic developments including targeted delivery of chemotherapy, novel radiation therapy, and immunotherapy.


Assuntos
Terapia de Alvo Molecular/métodos , Neuroblastoma/terapia , Criança , Humanos , Imunoterapia/métodos , Terapia de Alvo Molecular/tendências , Radioterapia/métodos
18.
Surg Clin North Am ; 99(3): 511-527, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31047039

RESUMO

Next-generation sequencing has enabled genome-wide molecular profiling of gastric and esophageal malignancies at single-nucleotide resolution. The resultant genomic profiles provide information about the specific oncogenic pathways that are the likely driving forces behind tumorigenesis and progression. The abundance of available genomic data has immense potential to redefine management paradigms for these difficult disease processes. The ability to capitalize on the information provided through high-throughput sequencing technologies will define cancer care in the coming decades and could shift the paradigm from current stage-based, organ-specific treatments toward tailored regimens that target the specific culprit pathways driving individual tumors.


Assuntos
Adenocarcinoma/genética , Neoplasias Esofágicas/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Gástricas/genética , Adenocarcinoma/classificação , Adenocarcinoma/terapia , Neoplasias Esofágicas/classificação , Neoplasias Esofágicas/terapia , Genômica , Sequenciamento de Nucleotídeos em Larga Escala/tendências , Humanos , Instabilidade de Microssatélites , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Neoplasias Gástricas/classificação , Neoplasias Gástricas/terapia , Terminologia como Assunto
20.
Rev Mal Respir ; 36(4): 433-437, 2019 Apr.
Artigo em Francês | MEDLINE | ID: mdl-31010759

RESUMO

Pulmonary arterial hypertension (PAH) is a severe and incurable cardiopulmonary disorder. Research from the past 10 years illustrates the complex and multifactorial aspects of PAH pathophysiology. Furthermore, latest advances in the field have led to a better understanding of the key components underlying this inadequate accumulation of pulmonary vascular cells within the pulmonary arterial walls, leading to pulmonary vascular remodelling. Among the underlying molecular and cellular mechanisms, pulmonary endothelial dysfunction, alterations of the inter-cell communications within the pulmonary arterial walls as well as defects of the inflammatory component and the loss of BMPRII activity play critical roles in the pathogenesis of the disease.


Assuntos
/etiologia , Imunidade Adaptativa/fisiologia , Autoimunidade/fisiologia , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Células Endoteliais/fisiologia , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/imunologia , Hipertensão Pulmonar/fisiopatologia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Miócitos de Músculo Liso/fisiologia , /imunologia , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiologia , Transdução de Sinais/genética , Remodelação Vascular/fisiologia
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