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
Lung cancer is a worldwide epidemic and despite platinum-based chemotherapy being the cornerstone of non-small cell lung cancer treatment, patient response rates to these regimens remain very low. Although resistance to cisplatin is multifactorial, DNA repair plays a critical role in cisplatin resistance. One of the most important goals in translational research is to investigate the clinical use of DNA repair pathways that may influence cisplatin chemosensitivity. Trying to understand the role of genes involved in DNA repair and response to treatment has become one of the main objectives of individualised chemotherapy. It is well known that chemosensitivity is individually predetermined, and the upregulation of mRNA transcripts has been linked to differential response to cytotoxic drugs. In this article, the authors try to highlight the more relevant aspects regarding these issues, primarily focused on the potential role of ERCC1, RRM1, XPD and BRCA1 expression profiling as predictors of anticancer drug efficacy.
