Major research programs in the Thoracic and Cardiovascular Surgery department include identification of oncogenes and tumor suppressor genes important in lung cancer development and progression, development of techniques to alter oncogene and tumor suppressor gene expression, investigation of genetic events in premalignant lesions, development of efficient viral and nonviral vectors for gene delivery to cancer cells, and application of these systems in human gene therapy.
Jack A. Roth, professor and director of the W.M. Keck Center for Innovative Cancer Therapies at MD Anderson, was among the first to identify and characterize a number of tumor suppressor genes for lung cancer and discover a way to deliver them to cancer cells using nanoparticles.
Gene-based prevention and treatment strategies:
- Identification of Oncogenes and Tumor Suppressor Genes
- Techniques to Alter Oncogene and Tumor Suppressor Gene Expression
- Investigation of Genetic Events in Premalignant Lesions
- Development of Efficient Viral and Nonviral Vectors for Gene Delivery to Cancer Cells
The goal of our research is to develop drugs that can be more effective at killing cancer cells and less toxic for patients.
Jack A. Roth, M.D.
Thoracic surgeon and researcher
Clinically Relevant Tumor Models
Patient-derived xenograft (PDX) models have emerged as robust preclinical models for drug development, molecular characterization of cancers, and strategic development of precision therapy. With the support of MD Anderson Lung Cancer Moon Shot Program and Lung Cancer SPORE Program, we have generated 150 lung PDXs for translational research of lung cancer. Most of these PDXs were generated from surgical NSCLC specimens, and a small number from biopsy or pleural fluid specimens. Moreover, we have completed targeted sequencing of 200 cancer-related genes for 20 PDXs and whole-exome sequencing for 62 PDXs. The availability of hundreds of PDXs of diverse histologic types and molecular profiles provides a unique opportunity for preclinical evaluation of novel therapeutic agents and identification of predictive biomarkers. Moreover, we are developing humanized PDX models that are reconstituted with human immune system, which will be used for preclinical evaluation of immunotherapy for lung cancer.
Novel Precision Medicine for Lung Cancer
The breakthrough discoveries in targeted therapy and immunotherapy have not only led to a new paradigm of biomarker-directed precision therapy but also greatly accelerated the development of novel anticancer drugs. We are now focusing on developing innovative combination therapies and predictive biomarkers for precision therapy of lung cancer, by evaluating their efficacies in molecularly annotated PDX models. These studies will be pursued through collaborations with the investigators in MD Anderson Lung Cancer Moon Shot Program, and/or in NCI PDXNet and ETCTN Programs.
Clinical trials have focused on the development of combined-modality treatment approaches involving novel chemotherapy agents, radiotherapy techniques and surgical approaches. These protocols represent a major collaborative effort with the departments of Thoracic/Head and Neck Medical Oncology, Gastrointestinal Oncology and Digestive Diseases and Radiation Oncology. Current protocols for lung cancer include both preoperative and postoperative adjuvant chemotherapy with novel agents.
Protocols combining chemotherapy, radiotherapy and surgery are being evaluated for esophageal cancer. A novel strategy of pulmonary perfusion with doxorubicin for sarcomatous lung metastases is being evaluated. A major collaboration with the Department of Thoracic/Head and Neck Medical Oncology is directed toward chemoprevention of second primary cancers in patients with early-stage lung cancer.
The Thoracic and Cardiovascular Surgery department has completed clinical trials to evaluate replacement of the p53 tumor suppressor gene by delivering a functional p53 tumor suppressor via retroviral and adenoviral vectors in patients with non-small cell lung cancer. New trials combining p53 gene replacement are planned in combination with radiotherapy and chemotherapy in collaboration with the Department of Thoracic/Head and Neck Medical Oncology.
Lung Cancer SPORE
The department is a recipient of a National Cancer Institute Specialized Program of Research Excellence (SPORE) in Lung Cancer grant jointly with The University of Texas Southwestern Medical Center in Dallas. This program has major projects focused on molecular early detection, susceptibility genes and chemoprevention of lung cancer.