University of California San Francisco

Thoracic Oncology Lab Research

The Thoracic Oncology Lab has been making great strides in both clinical and basic research over the past several years. We advanced cutting-edge therapeutics from in silico design and benchtop development with a first-in-class novel pan RAS inhibitor as well as a novel dual acting anti-PARP/anti-microtubule inhibitor, both in clinical trials. An international clinical trial for early-stage lung cancer is being conducted to test an innovative molecular risk stratifying diagnostic assay which has benefited thousands of patients. We have continued our basic research focused on developmental pathways exploited by thoracic malignancies and cancer in general, such as WNT and Hippo signaling. Ongoing studies for immuno-therapeutic approaches to strategically target extra and intracellular moieties in these pathways are currently underway.

We designed a 14 gene molecular assay to identify aggressive biology in early-stage non-small cell (adenocarcinoma) lung cancers and predict prognosis. This assay is being tested in a prospective, international, randomized clinical trial and is a CMS (Medicare) approved and reimbursed CLIA assay. We are able to predict and guide adjuvant therapy to cure patients with molecular stratified tumors of intermediate and high risk. The assay has saved thousands of early-stage NSCLC patients already and once approved in guidelines upon completion of the international Phase III trial will save tens of thousands of each year.

Our group was among the first to demonstrate that aberrant Wnt signaling appeared to cause lung cancer and mesothelioma through overexpression of Dishevelled (Dvl) proteins. Our lab also discovered the critical survival role of Wnt protein ligands as a survival mechanism. We derived a monoclonal antibody to target both the Wnt-1 and Wnt-2 genes and found that it induced apoptosis in cancer cells. Recently we developed a novel humanized antibody-drug conjugate (ADC). Anti-Wnt2-ADC has shown significant anti-tumor effects in vitro and in vivo in Wnt driven tumors including lung cancer, mesothelioma, pancreatic cancer among others. A Phase I clinical trial is expected to start within the near future. We are optimistic that this line of work will lead to new effective treatment for lung cancer, mesothelioma and other cancers.

Our Research
Principal Investigator: Liang You, Ph.D. The goal of this project is to test potential therapeutics for mesothelioma in our newly developed Cullin 4A (Cul4A)-midiated metastasis model in which mouse mesothelioma cells are directly injected into the pleural cavity of immune-competent mice and to better understand the role of Hippo/YAP signaling pathways in Cul4A-mediated mouse mesothelioma metastasis. This builds on past work in collaboration with Dr. Jian-Hua Mao, Dr. Zhidong Xu, Dr. Yi-Lin Yang, and Dr. David Jablons that investigated the ...
Principal Investigator: Johannes R. Kratz, MD Lung cancer is the leading cause of cancer death worldwide. Early detection is critical to effective treatment. The Kratz Lab, a core research lab in the Thoracic Oncology Program, is focused on elucidating diagnostic biomarkers and developing novel targeted therapies for treatment of lung cancer, mesothelioma and esophageal cancer. Using the latest DNA / RNA sequencing and gene expression techniques combined with a bioinformatics-driven systems biology approach, the Kratz lab is comparing the different ...
Principal Investigator: Csaba J. Peto, Ph.D. Csaba J. Peto, Ph.D. is a synthetic medicinal chemist. His primary research focus is the discovery and development of small molecule drug candidates for cancer therapy. Utilitzing his two decades of experience in the biotech industry, Dr. Peto designs and synthesizes compounds for multi-parametric optimization that target oncogenic signaling pathways. ...