Assuntos
Falência da Empresa , Neoplasias/economia , Neoplasias/terapia , Falência da Empresa/legislação & jurisprudência , Falência da Empresa/tendências , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Custos de Cuidados de Saúde/legislação & jurisprudência , Humanos , Oncologia/economia , Oncologia/legislação & jurisprudência , Oncologia/organização & administração , Neoplasias/patologia , Qualidade da Assistência à Saúde/economia , Qualidade da Assistência à Saúde/legislação & jurisprudência , Qualidade da Assistência à Saúde/organização & administração , Qualidade de Vida , Espanha , Organização Mundial da SaúdeRESUMO
Metformin is a biguanine, the most widely used antidiabetic drug for the treatment of type 2 diabetes. Some studies suggest that metformin decreases the incidence of cancer and cancer-related mortality in diabetic patients. Metformin activates the AMP-activated protein kinase (AMPK) pathway, a major sensor of the energy status of the cell and an inhibitor of mammalian target of rapamycin (mTOR) catalytic activity, inducing a decrease in blood glucose by decreasing hepatic gluconeogenesis and stimulating glucose uptake in the muscle. Some preclinical data supports the inhibition of tumour cancer cell growth associated with mTOR inhibition and a decrease in phosphorylation of S6K, rpS6 and 4E-BP1. Here we have summarised some of the preclinical data and data of many clinical trials that are exploring the true value of metformin for cancer patients, mainly breast and prostate cancer.
Assuntos
Antineoplásicos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Humanos , PrognósticoRESUMO
The cancer stem cell (CSC) theory is currently a very important field in cancer research. This theory states that tumours are organised in a hierarchical manner with a subpopulation of limited number called CSCs with the ability to self-renew and undergo asymmetrical divisions, giving rise to a differentiated progeny that represents most of the tumour populations. CSCs are metastatic and chemoresistant, two features that very likely contribute to the poor response of locally advanced lung cancer. CSCs have been identified in non-small-cell lung cancer cell lines as well as those from patient primary samples. A correlation has been found in terms of chemoresistance and bad prognosis in patient-derived samples enriched with CSCs, indicating that these cells are an important target for future therapy combinations. Therefore, understanding the biology and exploring cell markers and signalling pathways specific for CSCs of lung cancer may help in achieving progress in the treatment of the disease.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/citologia , Antígeno AC133 , Aldeído Desidrogenase/metabolismo , Antígenos CD/biossíntese , Antígenos CD34/biossíntese , Diferenciação Celular , Glicoproteínas/biossíntese , Humanos , Receptores de Hialuronatos/biossíntese , Oncologia/métodos , Metástase Neoplásica , Peptídeos , Transdução de Sinais , Fatores de Transcrição/metabolismo , Resultado do TratamentoRESUMO
Incorporation of antibodies as weapons for cancer therapy has meant a turning point in the survival, clinical and radiological response of many oncology patients. These drugs are effective, well designed missiles that either alone or in combination with chemotherapy are unavoidable weapons for breast, lung and colon cancer as well as for haematological tumours. In addition, incoming monoclonal antibodies (mAbs) and folder-like proteins will be incorporated into clinical practice in the near future. This review aims to discuss a few imminent indications of current mAbs that are used for solid tumours and to briefly introduce future mAbs to the reader.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Oncologia/tendências , Neoplasias/terapia , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/tendências , Terapia Combinada , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Oncologia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/imunologiaRESUMO
Gastric cancer is a leading cause of death worldwide. Nowadays, complete surgical resection and TNM at diagnosis are the main prognostic factors. In spite of this, many patients will have a recurrence after surgery and die within a few months or years. That means that we need more accurate prognostic factors to design specific approaches for individual patients. Chromosome instability is a feature of gastric cancer commonly associated to chromosomal aberrations that leads to major modifications of DNA content globally termed as aneuploidy. In this regard, many authors' opinions diverge regarding the clinical impact of aneuploidy. This review will summarise data on the clinical impact of aneuploidy on clinical practice, the biological mechanisms that underlie chromosomal instability that induces aneuploidy and the relevance of specific chromosomal aneuploidy to cancer biology.
Assuntos
Aneuploidia , Neoplasias Gástricas/genética , Animais , Centrossomo/metabolismo , Humanos , Fuso Acromático , Neoplasias Gástricas/patologiaRESUMO
Pancreatic cancer is a leading cause of cancer death. This devastating disease has the horrible honour of close to equal incidence and mortality rates. Late diagnosis and a constitutive resistance to every chemotherapy approach are responsible for this scenario. However, molecular biology tools in cooperation with translational efforts have dissected several secrets that underlie pancreatic cancer. Progressive acquisition of malignant, invasive phenotypes from pre-malignant lesions, recent revelations on core signalling pathways and new targeted designed trials offer a better future for pancreatic cancer patients. This review will summarise recent advances in the molecular biology of pancreatic cancer.
Assuntos
Neoplasias Pancreáticas/genética , Predisposição Genética para Doença , Humanos , Biologia Molecular , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapiaRESUMO
DNA repair pathways enable tumour cells to survive DNA damage induced by external agents such as therapeutic treatments. Signalling cascades involved in these pathways comprise the DNA-dependent protein kinase (DNA-PK), Ataxia-telangiectasia mutated (ATM), ATM and Rad3 related (ATR) and checkpoint kinases I and 2 (Chk1/Chk2), among others. ATM and ATR phosphorylate, respectively, Chk2 and Chk1, leading to activation of checkpoints. Chk2 acts as a signal distributor, dispersing checkpoint signal to downstream targets such as p53, Cdc25A, Cdc25C, BRCA1 and E2F1. A role of Chk2 as a candidate tumour suppressor has been suggested based on both mouse genetics and somatic tumour studies. We will discuss here the possible role of this kinase in human carcinogenesis and the possibility to use it as a target to increment DNA damage in cancer cells in response to DNA-damaging therapies.
Assuntos
Neoplasias/enzimologia , Proteínas Serina-Treonina Quinases/fisiologia , Animais , Quinase do Ponto de Checagem 2 , Dano ao DNA/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Humanos , Proteínas Serina-Treonina Quinases/antagonistas & inibidoresRESUMO
Castleman's disease (CD) is a rare disorder of uncertain aetiology characterised by massive proliferation of lymphoid tissue usually localised as mediastinal masses, although abdominal involvement has been reported. Localised forms are usually associated with a good prognosis, but several more aggressive multifocal variants have been observed. Two different histologic subtypes have been described: the hyaline vascular type, more common in unicentric CD and usually asymptomatic, and the plasma cell form. Unicentric CD may be associated with an increased risk of lymphoma, but there was no reported increased risk of other malignancies. A patient with plasma cell subtype unicentric CD localised in retroperitoneum associated with an adenocarcinoma of ileocaecal valve and liver metastasis is reported.
Assuntos
Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/patologia , Neoplasias do Colo/complicações , Espaço Retroperitoneal/patologia , Hiperplasia do Linfonodo Gigante/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicaçõesRESUMO
High-grade gliomas are the most common primary malignant brain tumours. Surgery, radiotherapy and chemotherapy are the cornerstone of actual treatment. In spite of large therapeutic efforts, overall survival is still poor. New molecular data allow a new molecular classification for high-grade gliomas and open a therapeutic window for targeted therapy. Molecular diagnostic tools may provide a basis for receptor-based therapies and enough information to personalise future treatments. In this regard, epidermal growth factor receptor (EGFR) is a target that will play a critical role in the management of glioma patients. This review summarises basic and preclinical data that support future use of therapies against EGFR.
Assuntos
Neoplasias Encefálicas/metabolismo , Receptores ErbB/metabolismo , Glioblastoma/metabolismo , Animais , HumanosRESUMO
Gliomas are the most common primary brain tumours. In keeping with the degree of aggressiveness, gliomas are divided into four grades, with different biological behaviour. Furthermore, as different gliomas share a predominant histological appearance, the final classification includes both, histological features and degree of malignancy. For example, gliomas of astrocytic origin (astrocytomas) are classified into pilocytic astrocytoma (grade I), astrocytoma (grade II), anaplastic astrocytoma (grade III) and glioblastoma multiforme (GMB) (grade IV). Tumors derived from oligodendrocytes include grade II (oliogodendrogliomas) and grade III neoplasms (oligoastrocytoma). Each subtype has a specific prognosis that dictates the clinical management. In this regard, a patient diagnosed with an oligodendroglioma totally removed has 10-15 years of potential survival. On the opposite site, patients carrying a glioblastoma multiforme usually die within the first year after the diagnosis is made. Therefore, different approaches are needed in each case. Obviously, prognosis and biological behaviour of malignant gliomas are closely related and supported by the different molecular background that possesses each type of glioma. Furthermore, the ability that allows several low-grade gliomas to progress into more aggressive tumors has allowed cancer researchers to elucidate several pathways implicated in molecular biology of these devastating tumors. In this review, we describe classical pathways involved in human malignant gliomas with special focus with recent advances, such as glioma stem-like cells and expression patterns from microarray studies.