For four years, Clare Weeden was on call for every lung cancer surgery across all Melbourne, Australia, hospitals. The PhD candidate at the University of Melbourne needed to be at her lab to receive fresh tissue samples for a project: isolating and analyzing the basal stem cells that repair our lungs from exposure to everyday contaminants like pollution and cigarette smoke. The process took up to six hours for each of the 140 samples she eventually collected, so that meant many late nights at the lab. She was sometimes there until 3 am.
Part of the process was making these lung stem cells grow into colonies (stem cells in general are really good at replicating). As Weeden collected more and more samples, she noticed that one of them hardly grew at all. She contacted the Victorian Cancer Biobank for information on the donor and was surprised to learn that this patient had never smoked. She immediately got medical histories for all of the other donors and identified a pattern: The basal stem cells of non-smokers had lower growth rates than those of smokers, and the more a person smoked, the higher the growth rate.
For a study published in PLOS Biology, she set out to learn how basal stem cells function and found that they work quickly to repair DNA damage from inhaled chemicals, but they're a little too fast for their own good—they make mistakes in the form of genetic mutations. If the cells have to do more repair work in, say, someone who smokes a lot, there's a greater chance of accumulating cancer-causing mutations. Nonsmokers can and do get lung cancer (cigarette smoke is just one risk factor) but Weeden theorized that these basal stem cells might be to blame for cancer-causing mutations in smokers specifically.
To test her theory, she compared the genetic signature of basal stem cells to various lung cancers and found that it was highly correlated with squamous cell carcinoma, a form of lung cancer directly tied to smoking (96 percent of people who have it are either smokers or former smokers). To her, this fingerprint was evidence that basal stem cells trigger lung squamous cell carcinoma in smokers. This is a brand-new finding: Doctors know that cancer is caused by DNA mutations when cells divide, and lung cancer is no different, but Weeden's research may have identified the specific cells where lung squamous cell carcinoma begins.
Watch her explain in her Aussie accent:
This discovery could help researchers develop or identify drugs to "turn off" the basal stem cells and stop lung cancer's progress, like researchers from her school did for BRCA1 breast cancer. But Weeden says any such drug wouldn't help people who still smoke; they'd have to quit. She added in a release: "This is particularly relevant as lung squamous cell carcinoma can occur in ex-smokers who have quit perhaps 20 or 30 years ago." Then again, she noted that smoking can cause other lung cancers that don't seem to be connected to basal stem cells like adenocarcinoma—so really, just quit.