Roth's research integrates clinical thoracic oncology with molecular and gene therapy approaches. His work spans randomized clinical trials, first-in-human gene-therapy protocols, systemic nanoparticle delivery of
tumor suppressor genes, and translational studies combining gene therapy with targeted agents and
immunotherapies.
Neoadjuvant and multimodality trials Roth was
principal investigator on seminal clinical trials that established a role for perioperative chemotherapy in resectable stage IIIA non-small cell
lung cancer. A randomized trial comparing perioperative chemotherapy plus surgery versus surgery alone showed a survival advantage for the combined approach.
Tumor suppressor gene therapy (p53) Beginning in the 1990s, Roth and collaborators developed retroviral and
adenoviral vectors expressing wild-type p53 and conducted early clinical trials delivering p53 to human tumors. He was principal investigator for the first tumor-suppressor gene therapy clinical trials approved by the NIH Recombinant DNA Advisory Committee and the
U.S. Food and Drug Administration. These trials evaluated intratumoral Ad-p53 (INGN 201 / Advexin) in lung and head-and-neck cancers and provided mechanistic and early efficacy evidence, including induction of p53-regulated apoptotic pathways and tumor regression when combined with radiotherapy. While adenoviral p53 constructs evaluated by Roth and collaborators formed part of the scientific basis for later commercialization efforts, the first regulatory approval for an adenoviral p53 product (
Gendicine) occurred in China in 2003; Roth's clinical development work in the
United States was influential in establishing feasibility and proof-of-principle for p53 replacement strategies.
Systemic nanoparticle gene delivery (TUSC2/FUS1) Roth led preclinical and clinical development of systemic nanoparticle-mediated delivery of tumor suppressor genes, notably
TUSC2 (FUS1). A Phase I trial of intravenously delivered TUSC2 nanoparticles in patients with advanced non-small cell lung cancer demonstrated uptake by tumors, expression in
tumor tissue, and downstream pathway effects with acceptable safety—providing the first clinical evidence for systemic nanoparticle gene delivery in lung cancer. Subsequent work from Roth's team has shown that TUSC2 delivery can modulate the tumor immune microenvironment and synergize with immune checkpoint blockade and targeted agents.
Translational programs and SPORE leadership Roth has been a leader in institutional and national translational initiatives. He has been co-principal investigator on major
National Cancer Institute programs, including an NCI Lung Cancer Specialized Programs of Research Excellence (SPORE), and has headed multidisciplinary teams integrating genomics, biomarker discovery, and early clinical trials. ==Education initiatives==