Understanding Lung Cancer in Individuals Who Never Smoked

November 22, 2022

Lahey Hospital & Medical Center (LHMC) is a world leader in the early detection of lung cancer. Most individuals developing lung cancer have a current or past history of smoking cigarettes. However, the rate of lung cancer diagnoses in people who have never smoked is on the rise. LHMC thoracic oncologists Paul J Hesketh, MD, FASCO, and AJ Piper-Vallillo, MD, along with Kimberly Rieger-Christ, PhD, vice president of Research Operations, are building on this work by undertaking novel research focused on early, potentially lifesaving screening for lung cancer among individuals who have never smoked cigarettes.

15 to 20 percent of people in the United States diagnosed with lung cancer annually have never smoked—and researchers are attempting to identify the group of those who never smoked at greatest risk of developing lung cancer. “What we do know is that people may have a combination of some genetic predisposition and exposures to environmental factors that together increase the risk for lung cancer,” explained Dr. Piper-Vallillo, medical oncologist at the Sophia Gordon Cancer Center.

According to Dr. Hesketh, people who never smoked are most often diagnosed with lung cancer at the latest stage of the disease, or stage 4, when the cancer has already spread. “Late diagnosis dramatically decreases life expectancy,” said Dr. Hesketh, director of the Sophia Gordon Cancer Center and Thoracic Oncology and director of the Lahey Health Cancer Institute. “The next step in reducing lung cancer deaths globally is developing a risk assessment model to identify those who never smoked, but who are at high risk of developing lung cancer, and to screen them.”

In her laboratory, Dr. Rieger-Christ is overseeing the development of a biorepository by collecting biospecimens from 200 patients who have never smoked and do not have lung cancer and from 100 individuals who never smoked who have lung cancer. The LHMC research team also will gather extensive demographic information about each group, including exposures to specific environmental toxins. “When we examine the DNA and RNA of never smoked with and without lung cancer, we may find differences in gene mutations and gene expression that could provide key insights into why some patients who never smoked are at risk for developing the disease,” said Dr. Rieger-Christ.

Lahey scientists are working with renowned epidemiologist Martin Tammemägi, PhD, senior scientist for Ontario Health and professor emeritus at Brock University and Andrea Borondy Kitts, MS, MPH, a lung cancer and patient advocate consultant, to develop a risk assessment model to predict which patients who never smoked may be at increased risk for developing lung cancer. While LHMC researchers work to discover differences in clinical and biomarker risk factors between study groups, the database will help validate the risk assessment model. “Early diagnosis dramatically affects treatment options and quality of life. For people diagnosed in stages 1, 2, and 3, our therapeutic intent is potentially to cure the cancer,” said Dr. Piper-Vallillo. “In stage 4, prognosis is much worse and cure is unlikely for the vast majority of patients.”

Closely aligned with Lahey’s CT lung screening program, one of the largest in the United States, this research is receiving initial funding from the Lory Molesky Never Smoked Research Fund at LHMC. Lory was diagnosed with stage 4 lung cancer in the summer of 2016 and treated by Dr. Hesketh. A year after Lory’s passing, to honor her late husband, Chia Shen, made a gift to support this exciting research. “Lory was a true Renaissance man who was passionate about life,” said Chia. “There is no better way to honor Lory than by helping to save lives.”