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Thoracic Surgery

Research Summary

Dr. Bueno’s research efforts are directed towards two related objectives. The first is to characterize the biologic behavior of malignant pleural mesothelioma and lung cancer at the molecular level and to utilize this information in order to design novel diagnostic and therapeutic modalities. The second is to develop translational tools from genomics to identify candidate prognostic and diagnostic markers for cancer, specifically mesothelioma and lung cancer. Dr. Bueno organized a collaborative team of clinicians (pathology, surgery and radiology) and basic scientists (molecular pathology, bioinformatics and statistics) to develop diagnostic and prognostic/predictive tests for patients with mesothelioma and lung cancer. They developed a new bioinformatic algorithm, the gene ratio test, which allows for the generation of specific clinical tests based on ratios of few specific genes. One example is the mesothelioma predictive test, which has been shown in prospective clinical trials to accurately identify those mesothelioma patients who will benefit from surgery. This test is currently being incorporated into the clinical management scheme of Mesothelioma patients at Brigham and Women’s Hospital. This algorithm received a broad patent in August 2008.

A second project has been the elucidation of the abnormal regulation of the apoptosis pathways in mesothelioma. Recent published studies have highlighted the over expression of several anti-apoptotic proteins as contributing to chemotherapy resistance in this malignancy. The laboratory is also actively participating in the International Mesothelioma Program’s tumor sequencing initiative. This work has demonstrated the heterogeneous nature of mesothelioma tumors and established a pipeline for the transcriptome sequencing of tumors as well as analysis of novel mutations and cancer genes.

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