RESUMO
Epidermal Growth Factor Receptor (EGFR) mutated Non Small Cell Lung Cancers (NSCLCs) are a molecularly subgroup of patients with peculiar clinic-pathological characteristics. Previous studies have suggested a possible interaction between oncogene status and metastatic behavior in non squamous NSCLCs with conflicting results. The aim of this study was to compare the different metastatic patterns, at baseline and during the course of the disease, in a cohort of 137 Caucasian patients with non-squamous NSCLC according to the EGFR mutational status and survival differences according to the different metastatic behavior. We observed unique metastatic distributions between EGFR-mutated and EGFR wild type non-squamous NSCLCs. These data support the hypothesis that tumor bio-molecular characteristics and genotype may influence the metastatic process in NSCLC and might help the development of enrichment strategies for tumor genotyping in these tumors, especially in the presence of limited tissue availability.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/etnologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Feminino , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , População Branca/genéticaRESUMO
Until recently, few therapeutic options were available for patients with castration-resistant prostate cancer (CRPC). Since 2010, four new molecules with a demonstrated benefit (sipuleucel-T, cabazitaxel, abiraterone, and denosumab) have been approved in this setting, and to-date several other agents are under investigation in clinical trials. The purpose of this review is to present an update of targeted therapies for CRPC. Presented data are obtained from literature and congress reports updated until December 2011. Targeted therapies in advanced phases of clinical development include novel androgen signaling inhibitors, inhibitors of alternative signaling pathways, anti-angiogenic agents, inhibitors that target the bone microenvironment, and immunotherapeutic agents. Radium-223 and MDV3100 demonstrated a survival advantage in phase III trials and the road for their introduction in clinical practice is rapidly ongoing. Results are also awaited for phase III studies currently underway or planned with new drugs given as monotherapy (TAK-700, cabozantinib, tasquinimod, PROSTVAC-VF, ipilimumab) or in combination with docetaxel (custirsen, aflibercept, dasatinib, zibotentan). The optimal timing, combination, and sequencing of emerging therapies remain unknown and require further investigation. Additionally, the identification of novel markers of response and resistance to these therapies may better individualize treatment for patients with CRPC.
RESUMO
Over the past few years, epidermal growth factor receptor has emerged as one of the most important targets in tumorgenesis and several drugs targeting signal transduction pathways have been developed. The first among these agents to be approved for the treatment of NSCLC was gefitinib, a potent, selective and reversible inhibitor of HER1/EGFR tyrosine kinase activity. The review summarizes its clinical development and the new therapeutic options, with particular focus on predictive markers of susceptibility to this drug.