More than 2 million people are diagnosed with lung cancer each year, making it the most common cancer worldwide. Non-small cell lung cancer (NSCLC) accounts for nearly 90% of lung cancer cases and is often incurable if it becomes metastatic.
Researchers at Yale Cancer Center and Smilow Cancer Hospital are leaders in lung cancer treatment breakthroughs. These include two recent lung cancer drug approvals by the U.S. Food and Drug Administration (FDA). The approvals, which bring hope to patients and their families, were based on research conducted at the Yale Cancer Center and Smilow Cancer Hospital. The approvals were also made possible by the results of national clinical trials led by Roy S. Herbst, MD, PhD, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital and associate cancer center director for translational research.
Getting New Non-small Cell Lung Cancer Treatment into the Clinic
The immunotherapy drug atezolizumab earned FDA approval in May 2020 for improvement in survival over standard chemotherapy for many patients with newly diagnosed (NSCLC). In December 2020, the FDA also approved a new tyrosine kinase inhibitor (osimertinib) for the treatment of adults with early-stage NSCLC with mutations in the epidermal growth factor receptor (EGFR) gene.
“These are exciting results that provide much-needed treatment options for our patients,” said Herbst. “But we continue our research to help find new therapeutics that could also be life-changing for many other patients with different types of this disease.”
For instance, patients with advanced NSCLC often develop resistance to current treatment options. To address this, Yale researchers are exploring how various immunotherapy drug combinations affect the development of resistance and disease progression. So far, they have had promising resulting in mice with lung tumors, as well as in a phase II clinical trial.
New Immunotherapy Drugs and Treatments for EGFR Mutant Lung Cancer
Yale Cancer Center is one of five cancer centers in the country to have a SPORE (Specialized Programs of Research Excellence) in Lung Cancer. The Yale SPORE in Lung Cancer, supported by an $11 million grant from the National Cancer Institute (NCI), harnesses the strengths of expertise in oncology, immunobiology, pharmacology, molecular biology, pathology, epidemiology, and addiction science to collaborate on projects focused on NSCLC. The focus is on three primary projects.
The first project is analyzing the immune suppressor capabilities of the Siglec-15 protein. The research seeks to determine the potential success of the inhibition of the Siglec-15 protein in patients with lung cancer and the development of predictive biomarkers for the protein. Based on this research, Lieping Chen, MD, PhD, United Technologies Corporation Professor in Cancer Research, professor of immunobiology, of dermatology, and of medicine (medical oncology), and co-director of the Cancer Immunology Program, developed an antibody drug called NC318, which is being investigated in clinical trials.
A second project is evaluating approaches to prevent tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. In a recent study, a research team from the Department of Pathology describes mechanisms of resistance to osimertinib, a tyrosine kinase inhibitor used to treat this type of cancer. The team, which included first author and pathology PhD student Jacqueline Starrett, co-author Robert Homer, MD, PhD, professor of pathology, and senior author Katerina Politi, PhD, associate professor of pathology, published their work in the journal Cancer Research.
In their study, the researchers found specific mutations in the EGFR gene that confer resistance to osimertinib and studied their therapeutic vulnerabilities. They also found that the type of resistance mutation observed was dependent on the baseline EGFR mutation in the tumor. The study provides insight into approaches to prevent and overcome resistance to tyrosine kinase inhibitors in EGFR mutant lung cancer.
The third project targets lung cancer metastasis and drug resistance in the central nervous system (CNS). Lung cancers are the major source of metastasis in the CNS. The project will help uncover the biological cause of brain metastasis and how therapies can be developed to target tumor-specific mutations.
Patients seeking lung cancer treatment can receive care at the Center for Thoracic Cancers. This multidisciplinary program provides cutting-edge evaluation and treatment to patients with thoracic malignancies in an efficient and coordinated manner at Smilow Cancer Hospital and at Smilow Cancer Hospital Care Center, with locations throughout Connecticut and Rhode Island. Through the center, patients have access to nationally recognized expert clinicians, who provide an organized, collaborative approach to cancer care, and access to the latest technologies and treatments.
Originally published March 19, 2020; updated May 16, 2022.