RESUMO
Biomarkers to identify subjects at high-risk for developing lung cancer will revolutionize the disease outlook. Most biomarker studies have focused on patients already diagnosed with lung cancer and in most cases the disease is often advanced and incurable. The objective of this study was to use proteomics to identify a plasma biomarker for early detection of lung lesions that may subsequently be the harbinger for cancer. Plasma samples were obtained from subjects without lung cancer grouped as never, current, or ex-smokers. An iTRAQ-based proteomic analysis was performed on these pooled plasma samples. We identified 31 proteins differentially abundant in current smokers or ex-smokers relative to never smokers. Western blot and ELISA analyses confirmed the iTRAQ results that demonstrated an increase of apolipoprotein E (APOE) in current smokers as compared to both never and ex-smokers. There was a strong and significant correlation of the plasma APOE levels with development of premalignant squamous metaplasia. Additionally, we also showed that higher tissue levels of APOE are seen with squamous metaplasia, supporting a direct relationship. Our analysis reveals that elevated plasma APOE is associated with smoking, and APOE is a novel predictive protein biomarker for early morphological changes of squamous metaplasia in the lung.
Assuntos
Apolipoproteínas E/análise , Biomarcadores Tumorais/sangue , Proteínas Sanguíneas/análise , Pulmão/patologia , Metaplasia/sangue , Fumar/sangue , Adulto , Idoso , Feminino , Humanos , Marcação por Isótopo , Masculino , Metaplasia/epidemiologia , Pessoa de Meia-Idade , Proteômica/métodos , Curva ROC , Fumar/epidemiologia , Adulto JovemRESUMO
Non-small cell lung cancer represents a group of heterogeneous diseases. The last decade witnessed significant progress in improving our understanding of the biology of non-small cell lung cancer, which led to the identification of several genetic targets. Those genetic targets were utilized to explain clinical phenomena, such as the occurrence of non-small cell lung cancer in never-smokers, to predict response to conventional chemotherapy and biological agents, and to explain and predict resistance to therapy. The progress in the treatment of non-small cell lung cancer in the last few years was based on a new generation of population-enriched clinical trials that utilized genetic targets such as somatic EGFR mutations and ALK-EML4 mutations. In this review we will discuss the available information about the key genetic markers of non-small cell lung cancer and the pivotal clinical trials that validate the use of those genetic markers in non-small cell lung cancer patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Marcadores Genéticos , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacosRESUMO
Acute myelogenous leukemia (AML) is characterized by uncontrolled proliferation of the cells of myeloid origin. It can present at all ages, but is more common in adults. It is one of the most common leukemias in adults and continues to pose significant challenge in diagnosis and long-term management.AML is a disease at the forefront of genetic and genomic approaches to medicine. It is a disease that has witnessed rapid advances in terms of diagnosis, classification, prognosis and ultimately individualized therapy. Newly diagnosed AML patients are now routinely stratified according to cytogenetics and molecular markers which guides long-term prognosis and treatment. On the other hand, with few exceptions, the initial treatment (also known as induction treatment) of AML has been 'one-size-fits-all'. It remains a great challenge for patients and physicians to consolidate and translate these advances into eventual success in clinic [1, 2].
Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Aberrações Cromossômicas , Humanos , Leucemia Mieloide Aguda/etiologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Prognóstico , Inibidores de Proteassoma/uso terapêuticoRESUMO
Epidermal growth factor receptor (EGFR) is a critical target in the treatment of nonsmall cell lung cancer (NSCLC). The mutations involving EGFR are more prevalent in patients of Asian ancestry, women, never smokers, and those with adenocarcinoma histology. Primary mechanism of resistance to EGFR-TKIs includes in frame insertion mutation in exon 20, de novo T790M mutation also on exon 20, activating mutations in KRAS, loss of PTEN, and amplification of c-MET whereas acquired resistance results from development of secondary alteration in ATP domain of T790M. There are many novel targeting agents in development to overcome resistance to EGFR TKIs.
