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1.
Adv Exp Med Biol ; 1131: 649-679, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646529

RESUMO

Multifunctional calcium/calmodulin-stimulated protein kinases control a broad range of cellular functions in a multitude of cell types. This family of kinases contain several structural similarities and all are regulated by phosphorylation, which either activates, inhibits or modulates their kinase activity. As these protein kinases are widely or ubiquitously expressed, and yet regulate a broad range of different cellular functions, additional levels of regulation exist that control these cell-specific functions. Of particular importance for this specificity of function for multifunctional kinases is the expression of specific binding proteins that mediate molecular targeting. These molecular targeting mechanisms allow pools of kinase in different cells, or parts of a cell, to respond differently to activation and produce different functional outcomes.


Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina , Regulação Enzimológica da Expressão Gênica , Terapia de Alvo Molecular , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Ativação Enzimática , Fosforilação
2.
Anticancer Res ; 39(11): 6241-6247, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704853

RESUMO

BACKGROUND/AIM: We performed multimodality therapy comprising preoperative chemotherapy, extrapleural pneumonectomy (EPP), and radiation therapy for patients with malignant pleural mesothelioma (MPM). Although multimodality therapy resulted in good prognosis, further improvement is required. Therefore, herein, we analysed the prognostic factors using surgical specimens and searched for suitable molecular targets to improve the prognosis after multidisciplinary treatment. PATIENTS AND METHODS: Forty-six patients with MPM underwent multimodality therapy. Paraffin-embedded surgical samples were used for immunohistochemistry to evaluate the expression of phosphorylated (p-) AKT, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and S6 ribosomal protein (S6RP). RESULTS: On univariate and multivariate analyses, significant differences were observed according to the histological type, pathological stage, and p-mTOR expression rate. CONCLUSION: The prognosis of MPM is affected by p-mTOR expression, suggesting that molecular-targeted treatment might be used during multimodal therapy for MPM.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/enzimologia , Mesotelioma/enzimologia , Proteína Quinase 1 Ativada por Mitógeno/análise , Neoplasias Pleurais/enzimologia , Serina-Treonina Quinases TOR/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/mortalidade , Mesotelioma/terapia , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Terapia de Alvo Molecular , Pemetrexede/administração & dosagem , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Pneumonectomia , Prognóstico , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo
4.
Rev Med Suisse ; 15(665): 1740-1745, 2019 Oct 02.
Artigo em Francês | MEDLINE | ID: mdl-31580017

RESUMO

The majority of early hearing disorders are of genetic origin. In view of the genetic heterogeneity, high-throughput sequencing analysis of a panel of genes involved in hearing loss is the most effective and economical approach, providing a diagnostic yield of around 40 % today. The determination of a molecular diagnosis makes it possible to: i) adapt the audiological care; ii) to search for possible somatic problems associated with so-called syndromic hearing loss; (iii) to avoid unnecessary additional examinations in isolated hearing loss; (iv) to establish accurate genetic counseling for relatives, or even to provide early diagnosis; and (v) to lay the foundation for potential future molecular hearing loss therapies in selected cases.


Assuntos
Perda Auditiva/genética , Criança , Surdez/diagnóstico , Surdez/genética , Surdez/terapia , Diagnóstico Precoce , Aconselhamento Genético , Perda Auditiva/diagnóstico , Perda Auditiva/terapia , Humanos , Terapia de Alvo Molecular , Síndrome
5.
Rinsho Ketsueki ; 60(9): 1108-1119, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597834

RESUMO

Conventional chemotherapy with cytarabine and anthracycline (often referred to as "7+3") has been used for many years in the treatment of acute myeloid leukemia (AML). Despite meaningful advances in areas of supportive care and transplantation, little progress has been made in developing new chemotherapy options. In 2018, The Food and Drug Administration (FDA) of the US approved several novel agents for AML treatment as follows: ivosidenib, an inhibitor of isocitrate dehydrogenase-1; venetoclax, a potent inhibitor of bcl2; and glasdegib, an inhibitor of hedgehog signaling pathway. Moreover, clinical trials of alvocidib (flavopiridol), an inhibitor of the CDK9, pevonedistat, an inhibitor of NEDD8, and APR-246, a reactivator of mutant p53, are in progress. These agents will either be incorporated into the conventional 7+3 regimen or combined with hypomethylating agents to improve the outcome of AML therapy, and the results will guide the next stage of precision medicine in the treatment of AML.


Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Benzimidazóis/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Ciclopentanos/farmacologia , Aprovação de Drogas , Flavonoides/farmacologia , Glicina/análogos & derivados , Glicina/uso terapêutico , Humanos , Terapia de Alvo Molecular , Compostos de Fenilureia/uso terapêutico , Piperidinas/farmacologia , Piridinas/uso terapêutico , Pirimidinas/farmacologia , Sulfonamidas/uso terapêutico , Estados Unidos , United States Food and Drug Administration
6.
Rinsho Ketsueki ; 60(9): 1243-1256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31597850

RESUMO

Multiple myeloma is a malignant plasma cell neoplasm that is incurable despite significant progress in treatment over the past several decades. The incorporation of novel agents and combinations into the MM treatment paradigm has resulted in improved survival and tolerability, as well as deeper responses including achieving a minimal residual disease negative state. The addition of new treatment options and combinations has added complexity in treatment selection for myeloma patients. The current strategy for newly diagnosed myeloma involves induction, consolidation, and maintenance therapy. However, nearly all myeloma patients will develop refractory disease. This highlights the need for more effective therapies targeting the myeloma cells and their microenvironment. In this article, we summarize current management of transplant eligible and ineligible newly diagnosed patients in both the upfront and relapsed refractory setting, highlighting risk adapted strategies. We also summarize emerging therapies, such as immune and targeted approaches, as well as drugs with novel mechanisms of action. Emerging strategies offer individualized treatment options and may ultimately offer the possibility of a cure for myeloma patients.


Assuntos
Mieloma Múltiplo/terapia , Gerenciamento Clínico , Humanos , Imunoterapia , Terapia de Alvo Molecular , Microambiente Tumoral
7.
Cancer Treat Rev ; 80: 101906, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31644971

RESUMO

Salivary gland cancer (SGC) is a rare malignancy consisting of 22 subtypes with different genetic, histological and clinical characteristics. This rarity and heterogeneity makes systemic treatment of recurrent or metastatic (R/M) disease challenging. Use of chemotherapy is scarcely studied and chemotherapy at best has moderate effects. New therapeutic strategies are therefore warranted, but advances made in SGC are lagging behind on advances made in more common cancers. By unraveling tumor characteristics of SGC, such as genetic alterations and protein expression profiles, therapeutic strategies tailored to the patient's tumor can be rationalized. This genomic profiling and mapping of immunohistochemical expression profiles is essential in the search for a suitable treatment approach. Thereby, it alleviates the paucity in systemic treatment options and can significantly alter the prognosis of patients with R/M SGC. This review aims to give a comprehensive overview of known genetic alterations and expression profiles amenable for targeted therapy in every histological subtype of SGC. We discuss the remaining knowledge gaps and the implications of these targets for future studies and personalized treatments, thereby aiding clinicians faced with this rare and heterogeneous type of cancer.


Assuntos
Neoplasias das Glândulas Salivares/classificação , Neoplasias das Glândulas Salivares/terapia , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Terapia de Alvo Molecular , Medicina de Precisão , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo
8.
Expert Opin Ther Pat ; 29(11): 909-919, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31566022

RESUMO

Introduction: Myeloid cell leukemia-1 (MCL-1) is an anti-apoptotic member of the B-cell lymphoma-2 (BCL-2) family of proteins that regulates apoptosis. Elevated levels of MCL-1 contribute to tumorigenesis and resistance, not only to conventional chemotherapies but also to targeted therapies, including the BCL-2 selective inhibitor venetoclax. Accordingly, researchers in both the pharmaceutical industry and academia have been actively seeking MCL-1 inhibitors in the quest for new anti-cancer drugs. Areas covered: This review covers the patent literature on the discovery and development of small-molecule inhibitors of MCL-1 since 2017. Expert opinion: Pharmacologic inhibition of MCL-1's oncogenic activity has certainly come of age with the discovery of numerous inhibitors spanning a variety of chemotypes that selectively inhibit MCL-1 in the picomolar range and with on-target cell activity. Furthermore, seminal research by Servier has demonstrated for the first time that MCL-1 inhibition is tolerable in animal models of cancer, paving the way for the six Phase 1 clinical trials that are currently underway for hematological malignancies, among other cancers. After more than a decade of research, the hurdles and obstacles are mostly behind us, and uncovering the therapeutic impact of disrupting the protein-protein interactions of MCL-1 in humans is imminent.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidores , Animais , Descoberta de Drogas/métodos , Humanos , Terapia de Alvo Molecular , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Patentes como Assunto
9.
Expert Opin Investig Drugs ; 28(11): 941-949, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31590579

RESUMO

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the burden of disease is increasing globally. Until recently, systemic therapies for HCC were limited and prognosis for advanced disease generally poor.Area covered: This article describes some recent phase I and II clinical trials for the treatment of HCC. We performed a search on Pubmed with keywords hepatocellular carcinoma, phase I clinical trial, phase II clinical trial, and immunotherapy. We also searched https://clinicaltrials.gov and identified relevant trials listed as active. Studies in progress or recently reported were conducted using novel therapies based on targets identified through molecular profiling of tumors or based on insights into immune system dysregulation in HCC. We also identified studies using drugs targeting recently discovered biomarkers such as endoglin or aldo-keto reductase 1c3. The major outcomes were safety and efficacy as measured by response rate, progression-free survival or overall survival.Expert opinion: HCC is a heterogeneous disease resulting from aberrations in intracellular signaling and immune system dysregulation. Thus, a multisystem approach will be required to deliver personalized therapy. Combination therapies are likely to be future options; it is also possible that modulation of the microbiome might form part of future treatment paradigms.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Drogas em Investigação/administração & dosagem , Drogas em Investigação/efeitos adversos , Drogas em Investigação/farmacologia , Humanos , Imunoterapia , Neoplasias Hepáticas/patologia , Terapia de Alvo Molecular , Sobrevida
10.
Expert Opin Investig Drugs ; 28(11): 977-988, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31594388

RESUMO

Introduction: Targeted therapies in cancer aim to inhibit specific molecular targets responsible for enhanced tumor growth. AKT/PKB (protein kinase B) is a serine threonine kinase involved in several critical cellular pathways, including survival, proliferation, invasion, apoptosis, and angiogenesis. Although phosphatidylinositol-3 kinase (PI3K) is the key regulator of AKT activation, numerous stimuli and kinases initiate pro-proliferative AKT signaling which results in the activation of AKT pathway to drive cellular growth and survival. Activating mutations and amplification of components of the AKT pathway are implicated in the pathogenesis of many cancers including breast and ovarian. Given its importance, AKT, it has been validated as a promising therapeutic target.Areas covered: This article summarizes AKT's biological function and different classes of AKT inhibitors as anticancer agents. We also explore the efficacy of AKT inhibitors as monotherapies and in combination with cytotoxic and other targeted therapies.Expert opinion: The complex mechanism following AKT inhibition requires the addition of other therapies to prevent resistance and improve clinical response. Further studies are necessary to determine additional rational combinations that can enhance efficacy of AKT inhibitors, potentially by targeting compensatory mechanisms, and/or enhancing apoptosis. The identification of biomarkers of response is essential for the development of successful therapeutics.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Desenvolvimento de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Terapia de Alvo Molecular , Neoplasias/patologia , Fosfatidilinositol 3-Quinase/metabolismo
11.
Expert Opin Investig Drugs ; 28(11): 989-1001, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612739

RESUMO

Introduction: Despite advancements over the last 2 years, outcomes for acute myeloid leukemia (AML) are poor; however, a greater comprehension of disease mechanisms has driven the investigation of new targeted treatments. Cyclin-dependent kinases (CDKs) regulate cell cycle progression, transcription and DNA repair, and are aberrantly expressed in AML. Targeting the CDK pathway is an emerging promising therapeutic strategy in AML.Areas covered: We describe the rationale for targeting CDK9 and CDK4/6, the ongoing preclinical and clinical trials and the potential of these inhibitors in AML. Our analysis included an extensive literature search via the Pubmed database and clinicaltrials.gov (March to August, 2019).Expert opinion: While CDK4/6 inhibitors are early in development for AML, CDK9 inhibition with alvocidib has encouraging clinical activity in newly diagnosed and relapsed/refractory AML. Preclinical data suggests that leukemic MCL-1 dependence may predict response to alvocidib. Moreover, MCL-1 plays a key role in resistance to BCL-2 inhibition with venetoclax. Investigational strategies of concomitant BCL-2 and CDK9 inhibition represent a promising therapeutic platform for AML. Furthermore, preclinical data suggests that CDK4/6 inhibition has selective activity in patients with KMT2A-rearrangements and FLT3 mutations. Incorporation of CDK9 and 4/6 inhibitors into the existing therapeutic armamentarium may improve outcomes in AML.


Assuntos
Antineoplásicos/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Terapia de Alvo Molecular , Animais , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Desenvolvimento de Medicamentos , Humanos , Leucemia Mieloide Aguda/patologia
12.
Expert Opin Investig Drugs ; 28(11): 951-965, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31614096

RESUMO

Introduction: Dementia with Lewy bodies (DLB) is an under-researched area despite being the second most common type of degenerative dementia after Alzheimer's disease. It is an area of unmet need with no approved symptomatic or disease-modifying therapies. The pharmacological management of DLB is complex and challenging because early trials of drugs for DLB have resulted in no demonstrable efficacy. Randomized controlled trials (RCTs) in the DLB population have only recently been initiated. Understanding results from previous and current clinical trials in DLB can provide insights for future research and development.Areas covered: We provide an overview of the DLB drug development landscape and the current treatment strategies. We reviewed ClinicalTrials.gov to identify all clinical trials for the treatment of DLB.Expert opinion: DLB drug development has significantly improved in recent years with eight agents now in clinical trials. However, more rigorous RCTs are urgently needed. Diagnostic criteria must be optimized to accurately diagnose patients for clinical trials and care. New biomarker strategies are necessary to improve diagnostic capabilities and trial designs, and novel drug targets should be identified to develop DLB specific disease-modifying therapies. Evaluating the current drug development landscape can provide insight into how best to optimize development practices.


Assuntos
Desenvolvimento de Medicamentos , Doença por Corpos de Lewy/tratamento farmacológico , Terapia de Alvo Molecular , Animais , Biomarcadores/metabolismo , Humanos , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Gan To Kagaku Ryoho ; 46(10): 1608-1610, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31631150

RESUMO

Recently, the interest in cancer genomic medicine has increased, owing to the powerful and cost-effective technology of next-generation sequencing(NGS), which allows rapid identification of a large number of gene mutations. TP53 mutations are frequently found in solid cancers, especially in esophageal squamous cell carcinoma(ESCC), wherein the frequency of TP53 mutation is considered to be 90% or more. However, there is no clinical targeted therapy as yet utilizing TP53. Here, we aimed to characterize TP53 mutations associated with ESCC, in order to assess its feasibility as a therapeutic target. We extracted DNA and RNA from specimens of ESCC patients and analyzed them using NGS, which revealed different TP53 mutations. Based on previous reports, it is considered that different TP53 mutations lead to different functions of the protein, and subsequently account for varied prognosis in squamous cell carcinoma of the head and neck. We also performed cell viability assay using ESCC cell lines with different TP53 mutations and 2 kinds of p53-targeted drug and found differences in the growth inhibition of the cell lines. Although individual treatment can be determined depending on the type of TP53 mutation, it would be necessary to further examine the interaction of TP53 with other genes to determine its therapeutic efficacy as a target.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Terapia de Alvo Molecular , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Genômica , Humanos , Mutação , Proteína Supressora de Tumor p53
14.
Ther Umsch ; 76(4): 167-172, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31498036

RESUMO

Nuclear medicine diagnostics, therapy and theranostics in the context of modern oncology Abstract. Nuclear medicine deals with imaging, therapy and theranostics using radioactive elements bound to targeted carrier molecules, so-called radiotracers. Modern oncology in particular benefits from the increasing diagnostic possibilities, for example in the context of increasingly precise tumour spread diagnostics or the early measurement of tumour response under targeted therapies. Modern nuclear medicine also offers new and innovative methods for the treatment of special types of tumours. For example, new therapies are available to treat metastatic prostate cancer, while other methods, such as breast and lung cancer or pancreatic cancer, are currently being tested in clinical trials. Nuclear medicine is complemented by theranostics, which combines therapeutic and diagnostic methods. Particularly in modern, personalized oncology with all its targeted therapies, these methods benefit from predicting therapy and high response rates.


Assuntos
Neoplasias/diagnóstico , Neoplasias/terapia , Medicina Nuclear , Nanomedicina Teranóstica , Humanos , Oncologia , Terapia de Alvo Molecular
15.
Ther Umsch ; 76(4): 179-185, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31498038

RESUMO

Molecularly-targeted anticancer treatments - a short appraisal Abstract. Molecularly-targeted or personalized systemic treatment has substantially transformed modern oncology, and has improved the prognosis of many tumor entities, in particular advanced solid and hematological malignancies. The bulk of molecularly-targeted anticancer drugs comprise small orally administered molecules, most prominently the tyrosine kinase inhibitors (TKI). The respective tumor entities treated by those drugs typically harbour specific genetic aberrations that we often call 'driver mutations', referring to their transforming and tumorigenic properties. Molecularly-targeted anticancer drugs fit to these genetic aberrations as they are able to specifically inhibit growth-stimulating signals. The success story of modern TKI's started 1999 with the use of the anti-BCR / ABL TKI imatinib in chronic myelogenous leucemia (CML) that enables those patients to achieve a virtually normal life expectancy. Since then, many molecularly-targeted anticancer drugs and TKI's have been approved for a wide range of malignancies. The next level of personalized oncological treatment will have to deal with much less frequent genetic aberrations that are inherently more difficult to spot in the tumor and to study. Newer techniques including next-generation sequencing (NGS) will help cancer specialists to screen their patients for genetic aberrations and get the most benefit from personalized oncology.


Assuntos
Antineoplásicos , Terapia de Alvo Molecular , Neoplasias/diagnóstico , Neoplasias/terapia , Medicina Nuclear , Resistencia a Medicamentos Antineoplásicos , Humanos , Oncologia
17.
Cancer Treat Rev ; 79: 101887, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31491661

RESUMO

Small cell lung cancer (SCLC) was defined as a "recalcitrant cancer" because of its dismal prognosis and lack of outcome improvements in the last 30 years. Immunotherapy with checkpoint inhibitors revolutionized treatment in many cancer types and results from the IMpower133 study, a double-blind placebo-controlled phase III trial, showed overall survival benefit for atezolizumab when added to standard platinum-etoposide chemotherapy in first-line SCLC setting for the first time since years. Trials with other checkpoint inhibitors, e.g. pembrolizumab, durvalumab, nivolumab and ipilimumab, are ongoing in various settings, but, to date, there are no defined factors to identify patients who are more likely to benefit from such treatments. This review summarizes results of immunotherapy trials in SCLC for first-line, maintenance and further-line therapies for single-agents and combinations with checkpoint inhibitors. Predictive factors from these trials are reviewed in order to identify their clinical value, with particular emphasis on PD-L1 expression on both tumor cells and in stroma, especially in pembrolizumab-treated patients, and tumor mutational burden, for patients treated with the ipilimumab and nivolumab combination.


Assuntos
Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/terapia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Imunomodulação/efeitos dos fármacos , Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
18.
Magy Onkol ; 63(3): 239-245, 2019 09 18.
Artigo em Húngaro | MEDLINE | ID: mdl-31538441

RESUMO

Skin cancers represent the most common type of malignancy. The incidence rate of melanoma and non-melanoma skin cancer depicts a continuous rise worldwide, which is attributed mainly (but not exclusively) to the growing incidence of non-melanoma skin cancer in the elderly population. Most skin cancer types are sensitive to immunotherapy. Melanoma, Merkel cell carcinoma, cutaneous squamous cell carcinoma showed response rates of at least 40% for PD-1 inhibitor therapy as reported in recent articles. In this article we review the current and future immunotherapy agents and procedures for skin cancers.


Assuntos
Imunoterapia/mortalidade , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Carcinoma de Célula de Merkel/imunologia , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/terapia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Intervalo Livre de Doença , Feminino , Humanos , Hungria , Masculino , Melanoma/imunologia , Melanoma/patologia , Melanoma/terapia , Terapia de Alvo Molecular/métodos , Prognóstico , Medição de Risco , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Análise de Sobrevida , Resultado do Tratamento
19.
Cancer Radiother ; 23(6-7): 662-665, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473087

RESUMO

Chemoradiotherapy is now considered the standard of care for many locally advanced diseases. Cytotoxic drugs have been largely evaluated in this setting, with cisplatin and 5FU the most often used drugs. A large amount of pre-clinical studies has demonstrated the synergy between both modalities. Concomitant administration seems the more beneficial in many diseases. Emergence of new approaches, combining targeted therapies and radiotherapy (RT) is now a reality. The main example is the association of cetuximab and RT in head and neck carcinomas, even if, 14 years after the initial publication, the best way to use it is still unknown. New compounds as inhibitors of DNA-repair or immune checkpoints are under investigation and showed early promising results.


Assuntos
Antineoplásicos/administração & dosagem , Quimiorradioterapia/tendências , Neoplasias/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/administração & dosagem , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Reparo do DNA/efeitos dos fármacos , Docetaxel/administração & dosagem , Esquema de Medicação , Fluoruracila/administração & dosagem , Humanos , Terapia de Alvo Molecular/métodos , Órgãos em Risco/efeitos da radiação , Lesões por Radiação/prevenção & controle , Fatores de Tempo
20.
Cancer Radiother ; 23(6-7): 708-715, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31477442

RESUMO

Stereotactic radiation therapy of brain metastases is a treatment recognized as effective, well tolerated, applicable for therapeutic indications codified and validated by national and international guidelines. However, the effectiveness of this irradiation, the evolution of patient care and the technical improvements enabling its implementation make it possible to consider it in more complex situations: proximity of brain metastases to organs at risk; large, cystic, haemorrhagic or multiple brain metastases, combination with targeted therapies and immunotherapy, stereotactic radiotherapy in patients with a pacemaker. This article aims to put forward the arguments available to date in the literature and those resulting from clinical practice to provide decision support for the radiation oncologists.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana/métodos , Órgãos em Risco , Radiocirurgia/métodos , Neoplasias Encefálicas/patologia , Tronco Encefálico , Hemorragia Cerebral/complicações , Terapia Combinada/métodos , Contraindicações de Procedimentos , Humanos , Imunoterapia , Imagem por Ressonância Magnética/efeitos adversos , Terapia de Alvo Molecular , Nervo Óptico , Marca-Passo Artificial , Carga Tumoral
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