The Fred Hutch-UW-Seattle Children’s Cancer Consortium is the NCI-designated comprehensive cancer center for Washington state and is supported by a large renewable Cancer Center Support Grant, which is organized into 9 research programs, including Lung Cancer. The Lung Cancer program is led by Dr. McGarry Houghton and supports research activities which span the molecular basis of cancer, immunology, translational research and cancer etiology prevention and outcomes. A centerpiece of the Lung Program is an NCI-funded Lung Specialized Program in Research Excellence (SPORE), also led by Dr. Houghton, which supports clinical trials, translational research spanning bench to bedside and career development activities. The pulmonary group at Fred Hutch also maintains the Lung biorepository which integrates biospecimens and clinical data for patients seen in the Lung Cancer Early Detection and Prevention Clinic.
Pre-Clinical Research
The Houghton Lab studies the immune cell composition and function in solid tumor malignancies, most prominently in non-small cell lung cancer (NSCLC). The group has established a platform to combine the study of human tissue specimens and mouse models of cancer to address key questions ranging from mechanisms of immune escape and treatment failures to the identification of novel biomarkers for lung cancer early detection. This platform has revealed an essential role for myeloid lineage cells—particularly neutrophils—in excluding tumor-reactive lymphocytes from the malignant portion of tumors. The current focus of the lab is to determine the mechanistic basis of lymphocyte-excluded NSCLCs and to develop therapeutic strategies to circumvent their exclusion.
Housed within the Division of Human Biology at Fred Hutch, the goal of Dr. Jared Mayers and his research team is to decipher the metabolic behaviors of microbes as they cause disease in humans. They use an interdisciplinary approach combining in vivo multi-omics with models of disease, biochemistry, genetics, and chemical biology to investigate topics ranging from acute infections to chronic disease-associated shifts in microbiomes. They are particularly interested in projects with implications for antibiotic resistance, structural lung disease, and cancer development.
The Lung SPORE Histopathology and Biospecimen Core, supported by the Lung SPORE, also serves as the central biorepository for most lung cancer tissue and blood collection protocols at Fred Hutch. The Core maintains a biorepository of archival lung cancer specimens, blood and plasma samples, and bronchoalveolar lavage (BAL) fluid. In addition to assisting Consortium investigators with requests for specimens, the Core can provide assistance with: tissue sample processing and storage, basic histology, single color chromogenic immunohistochemistry (IHC), multiplexed fluorescent immunohistochemistry (M-IHC), digital image analysis, and tissue microarray (TMA) design and construction, spatial transcriptomics, quantitative image analysis, and data sharing and exploration.
Prevention
Within the Public Health sciences Division of Fred Hutch, Dr. Matty Triplette leads a transdisciplinary research program focused on improving implementation of lung cancer screening inclusive of tobacco cessation. His lab uses community-engaged methodologies, human-centered design principles and implementation science to build, adapt, test and evaluate multi-level interventions to support lung cancer prevention in underserved and high-risk communities. His current projects include community-embedded and pragmatic clinical trials of interventions which span system-focused and/or behavioral interventions to support lung cancer screening care completion.
Clinical and Translational Research
Within the Clinical Research Division at Fred Hutch, Dr. Viswam Nair conducts research focused on integrating molecular and imaging biomarkers in lung cancer with existing clinical algorithms for more precise detection and treatment. A more recent strategy has been to utilize proximal fluids that are sampled in relevant tumor biomarkers through bronchoscopic sampling of the lung. Within this program, current projects include minimally invasive genomic profiling of cancer and cellular phenotyping of lung cancer during the early and progressive stages of lung cancer.
Interventional Trials
The Lung SPORE provides ongoing resources for therapeutic trials for patients within lung cancer. The following represent of examples of clinical trials with Division Co-Investigators:
- SX-682 With Pembrolizumab for the Treatment of Metastatic or Recurrent Stage IIIC or IV Non-Small Cell Lung Cancer
This phase II trial tests whether the CXCR1/2 inhibitor SX-682 (SX-682), in combination with pembrolizumab, is effective for treating patients with recurrent or metastatic stage IIIC or IV non-small cell lung cancer. - Bomedemstat and Maintenance Immunotherapy for Treatment of Newly Diagnosed Extensive Stage Small Cell Lung Cancer
This phase I/II trial studied the side effects of bomedemstat and maintenance immunotherapy with atezolizumab for treatment of patients with newly diagnosed extensive stage small cell lung cancer.
