RESUMO
Primary lung cancer may arise from the central (bronchial) or peripheral (bronchiolo-alveolar) compartments. However the origins of the different histological types of primary lung cancer are not well understood. Stem cells are believed to be crucial players in tumour development and there is much interest in identifying those compartments that harbour stem cells involved in lung cancer. Although the role of stem cells in carcinogenesis is not well characterised, emerging evidence is providing new insights into this process. Numerous studies have indicated that lung cancer is not a result of a sudden transforming event but a multistep process in which a sequence of molecular changes result in genetic and morphological aberrations. The exact sequence of molecular events involved in lung carcinogenesis is not yet well understood, therefore deeper knowledge of the aberrant stem cell fate signalling pathway could be crucial in the development of new drugs against the advanced setting.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/etiologia , Proteínas Hedgehog/fisiologia , Neoplasias Pulmonares/etiologia , Receptores Notch/fisiologia , Células-Tronco/fisiologia , Proteínas Wnt/fisiologia , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Neoplasias Pulmonares/genética , Receptores Notch/genética , Receptores Notch/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Proteínas Wnt/genética , Proteínas Wnt/metabolismoRESUMO
INTRODUCTION: CNS metastases mean a great challenge. It has been suggested that the brain metastases incidence could be high in metastasic breast cancer patients receiving trastuzumab based-therapies. MATERIAL AND METHODS: We performed a descriptive analysis of our experience in this setting. 86 patients met the criteria (From Oct/99 to Oct/03). RESULTS: CNS progression occurred in 17 patients (19.5%). Mean age of CNS progression disease patients was 45.4 years while mean age for all the patients was 50.5 years. Response rate for the entire group of patients was: OR 39.7%; CB (OR + SD) 69%. Response rate to trastuzumab based-therapy was OR 82.4% and CB 88.2 at the time of CNS progression. Median time from the start of trastuzumab therapy up to the CNS progression was 10 months. OS was 23.4 weeks. CONCLUSIONS: The incidence of CNS involvement is high in young metastasic breast cancer women responding to trastuzumab-based therapies. This may lead to prophylactic cranial irradiation strategies or to the early detection in asymptomatic patients to improve surgery or radiosurgery results in these patients.