Researchers at Washington University School of Medicine in St. Louis are leading a nationwide study to identify patients with early-stage lung cancer who are at high risk for cancer recurrence, even after surgery and chemotherapy seem to have eliminated their tumours. The research is supported by a $5.3 million grant from the National Cancer Institute of the National Institutes of Health (NIH).
Non-small cell lung cancer is the most common cause of cancer-related death worldwide and is largely caused by smoking. If caught before it spreads to other parts of the body, this type of lung tumor can sometimes be cured with surgery and chemotherapy. But about half of those patients will experience a recurrence of lung cancer, and doctors have no way of identifying which patients are most at risk of having their tumors come back.
“We don’t have a test that we can do right after surgery to analyze the tumor and predict how the cancer will behave in the future, even in early-stage lung cancer,” the lead researcher said. Ramaswamy Govindan, MD, Anheuser Busch Endowed Chair in Medical Oncology at the University of Washington. “This ability to predict recurrence will become even more important as our lung cancer screening programs increase and our imaging technology improves as we diagnose more stage 1 disease. We want to see if we can identify molecules in the tumor – DNA, RNA or proteins, for example – which, when present, predict which tumors will recur and which will not.
Govindan and his colleagues from Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine will analyze tumor samples from patients participating in a group of nationwide clinical trials aimed at improving therapies for lung cancer. The trials, also co-led by Govindan, are being conducted at 1,242 sites across the country and include around 8,000 patients.
The suite of Phase 3 trials – called Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials (ALCHEMIST) – includes investigations into the effectiveness of a drug called erlotinib, an EGFR inhibitor for patients with tumor-bearing tumors of a specific mutation in the EGFR embarrassed. Another study will examine the effectiveness of checkpoint immunotherapy for patients who do not have this specific mutation. Patients receiving the experimental therapies will also receive surgery and standard chemotherapy, and their outcomes will be compared to those of patients receiving surgery and standard chemotherapy alone.
The new grant will support a Center for Translational Proteogenomics Research, led by the University of Washington and their collaborators at the Broad Institute of MIT and Harvard, which will analyze lung tumors from a representative sample of patients participating in these trials. The analysis will include a deep dive into tumor genomics and proteomics, meaning they will look for emerging patterns at the gene and protein level that could signal that a tumor is likely to come back. The research center is part of the NCI’s Clinical Tumor Proteomics Analysis (CPTAC) Consortium.
“The advantage of doing this analysis within the framework of existing clinical trials is that we can identify patients who will fare poorly not only after standard treatment – surgery and chemotherapy – but also among those who have also received inhibitors of EGFR or immune checkpoint inhibitors in addition to standard therapy,” Govindan said. “It also means that we could use protein-based biomarkers to identify patients who may do well with these various strategies treatment.
“We are optimistic that this comprehensive analysis from well-selected samples collected in a clinical trial will provide the best conditions for discovering biomarkers of cancer recurrence at the gene and protein level,” he said. added. “If we know who is at high risk for recidivism, we can focus our research on that group. We can study the biology of these misbehaving tumors to find out what drives them, which could lead to innovative new therapies.