While at the NCI, Dr. Roth completed the first randomized clinical trials of neoadjuvant chemotherapy for squamous carcinoma of the esophagus and open lung biopsy in immunocompromised patients with diffuse pulmonary infiltrates. At UTMDACC, Dr. Roth has initiated and acted as the principal investigator of the first gene therapy trials for lung cancer. Dr. Roth has spearheaded the development of institutional multidisciplinary protocols in thoracic oncology and was the principal investigator of the first randomized trial showing survival benefit with neoadjuvant chemotherapy in stage IIIA resectable lung cancer.
Among his landmark achievements, Dr. Roth was principal investigator for the first tumor suppressor gene therapy clinical trials approved by the National Institutes of Health Recombinant DNA Advisory Committee and the U.S. Food and Drug Administration. Approval for those historic protocols was based on his demonstrating feasibility and efficacy through laboratory and preclinical studies. His team showed that restoration of function for a single normal tumor suppressor gene could mediate regression of human cancers in vivo, helped identify and characterize a number of novel tumor suppressor genes on chromosome 3, and found that systemic delivery of tumor suppressor genes using a nanoparticle vector could effectively treat disseminated human lung cancer in animal models. These observations led Dr. Roth and colleagues to initiate the first clinical trial using nanoparticles to deliver genes systemically. Cancer gene therapy developed in his laboratory became the first gene therapy to be approved for human use. In addition to being an international leader in developing gene therapy for lung and other cancers, he has trained a new generation of outstanding surgical oncologists and laboratory researchers who are applying his philosophy of excellence throughout the world.