Dr. Joshua Campbell has been immersed in the field of lung cancer for several years and wanted to find a better way to diagnose squamous cell lung cancer patients, a subtype of non-small cell lung cancer, while the cancer is in early stages. “There is a huge need for research in this area,” he notes. “Improving early detection techniques will be key to improving survival rates for patients with squamous cell lung cancer.”
Squamous cell lung cancer is typically found in the main airways of the lungs and is more strongly associated with smoking than any other type of non-small cell lung cancer. Other factors such as age, family history, environmental factors, and exposure to secondhand smoke can also increase risk for squamous cell lung cancer. Approximately 30% of all lung cancers are classified as squamous.
Patients at increased risk for squamous cell lung cancer can be screened by bronchoscopy, a technique in which a thin tube with a tiny camera attached to one end takes images of the patient’s main airways to look for abnormal regions. These regions can then be biopsied to determine if the patient has squamous cell lung cancer. Although many of these abnormalities are technically classified as premalignant lesions, they often either resolve by themselves or do not progress to become malignant. This leaves physicians in a difficult position, as they do not have the ability to determine which of these regions will likely progress to cancer.
Dr. Campbell’s goal was to study repeat biopsy samples taken from the same patients year after year in order to identify the genetic mutations that were only found in the regions that became cancerous. These mutations could become a test panel for early signs of squamous cell lung cancer. If a premalignant lesion tested positive for these mutations, it could be monitored closely or even treated.
Dr. Campbell found an appropriate set of biopsy samples for this research through a collaboration with Dr. Avrum Spira at Boston University School of Medicine and Dr. Mary Reid at Roswell Park Comprehensive Cancer Center in New York. The samples, ideal for studying premalignant lesions, were taken from a group of patients at high risk for squamous cell lung cancer who were being regularly and repeatedly screened with bronchoscopy.
In 2016, Dr. Campbell applied for and was granted a Career Development Award from LUNGevity Foundation to accelerate this critical research. “The three-year award from LUNGevity has been great,’’ he says. “My professional network of researchers has really grown because of it. And scientifically, it has helped me get my lab off the ground. The research work has gone much faster because I have been able to perform higher-quality, deep sequencing of the DNA, and hire bioinformatics analysts to help manage the large amounts of data.”
Over the course of this project, the Campbell laboratory has amassed massive amounts of computational data—over 25 terabytes—consisting of whole-exome and deep-targeted sequencing of premalignant samples. Using this data and data previously generated by The Cancer Genome Atlas, Dr. Campbell and collaborators from the Center for Cancer Genome Discovery at Dana-Farber Cancer Institute created a new comprehensive panel that tests for approximately 50 genetic markers that are associated with squamous cell and adenocarcinoma lung cancers. “It is the most up-to-date lung cancer sequencing panel right now,” explains Dr. Campbell. “And because we studied the genomic sequences so deeply, the panel can identify mutations that are only present in a small proportion of cancer cells within the biopsy.”
While Dr. Campbell’s team has validated the testing panel on a small scale, the panel now requires validation on a larger scale before it can be implemented into routine practice. This involves many high-risk individuals being screened over many years to document which lesions (and which mutations) ultimately result in squamous cell lung cancer. If Dr. Campbell’s panel accurately predicts malignancy, the panel could become widely used by physicians to help identify patients who are at increased risk of squamous cell lung cancer. “It should help us to have a much better idea of which lesions to go after. We should see a decrease in patients with invasive squamous cell lung cancer.”
In addition to finding avenues to evaluate his testing panel on a larger scale, Dr. Campbell will also continue his research to understand the underlying mechanisms of squamous cell lung cancer. Through innovative new techniques, he plans to study the genes in individual premalignant cells to gain a more thorough understanding of how squamous cell lung cancer develops.
“The more we can learn about squamous cell lung cancer, the closer we will get to preventing and curing it,” notes Dr. Campbell. “And ultimately, that’s what we are striving for.”
Juhi Kunde, MA, is a science writer for LUNGevity.