Potential Breakthrough in Lung Cancer Prevention
Researchers have made a significant discovery that could aid in preventing lung cancer, which unfortunately has the highest mortality rate among all cancers globally. A team of over 80 scientists, collaborating across four continents, found a specific set of proteins in the blood that can predict the onset of lung cancer more than five years prior to an official diagnosis. They also uncovered preliminary evidence suggesting that a common anti-inflammatory medication may greatly lower the lung cancer risk for individuals with high levels of these proteins linked to inflammation.
However, more work is necessary before these proteins can be used in patient testing, and a randomized trial is essential to confirm whether the drug can effectively prevent lung cancer. Experts, reflecting on the findings published recently in the journal Cell, believe this research marks a promising step toward a long-cherished public health goal.
“For a long time, preventing lung cancer has been a sort of elusive quest,” mentioned Dr. Douglas Arenberg, a University of Michigan professor of medicine not involved in the research. The authors may have pinpointed a biological marker that not only determines risk but also indicates the potential benefits of a specific drug for prevention.
Over the past twenty years, there have been substantial advancements in lung cancer management, mainly due to screening programs that allow for earlier detection alongside targeted treatments and immunotherapies that can extend life for patients, even in advanced stages. Still, lung cancer remains the most frequently diagnosed cancer, with fewer than a third of patients surviving beyond five years.
“In my opinion, prevention is key,” said Dr. Charles Swanton, an oncologist and clinical director at the Francis Crick Institute in the UK, who was a senior author of the study. Together with Dr. Tej Pandya, a Ph.D. student, and their research team, they analyzed a collection of 48,000 blood samples from the UK Biobank, utilizing machine learning to identify 14 proteins tied to lung cancer development. By factoring in the presence of these proteins along with a patient’s age, smoking habits, and prior lung conditions, they predicted lung cancer development more accurately than current leading risk assessment models.
The validity of the 14-protein signature was confirmed through eight additional datasets worldwide, including samples from a Taiwan study which primarily involved non-smokers.
In experiments using mouse and cell models, the scientists demonstrated that these proteins escalated when a particular inflammatory pathway was activated, a pathway known to be influenced by factors like smoking and air pollution.
This supports the idea that lung cancers may not solely stem from genetic mutations due to smoking or pollution but might also involve inflammation. Dr. Swanton emphasized that “smoke induces mutations and inflammation, which together foster cancer.” They noted that higher levels of this protein signature were also present in individuals who later developed chronic obstructive pulmonary disease and pulmonary fibrosis, hinting at a shared inflammatory response underlying all three conditions.
This is particularly promising because targeting inflammation might be a strategy to address the issue before cancer manifests. The researchers revisited data from 4,650 participants in a randomized trial evaluating canakinumab, a drug that inhibits the same inflammatory pathway linked to the 14-protein signature. Though the trial mainly showed a modest benefit in reducing heart attacks, it also indicated a decreased occurrence of lung cancer in those receiving the drug.
The study revealed that canakinumab halved lung cancer risk among 2,300 trial participants with elevated levels of the 14 proteins. Dr. Swanton recently joined Novartis’ board, the manufacturer of canakinumab, but he equated the drug’s potential to that of statins: identifying patients with a specific marker (high LDL cholesterol) enables effective treatment that significantly lowers heart attack and stroke risks. “This may be akin to finding an LDL for cancer,” he stated.
Yet, the protein signature still requires validation through further studies, and a practical test must be developed for clinical use. Most importantly, a clinical trial is essential to establish canakinumab’s effectiveness in preventing lung cancer.
“The big question remains,” noted Dr. Roy S. Herbst, head of medical oncology and hematology at Yale School of Medicine. “Will it truly be significant? Can we intervene effectively at the right time to prevent cancer?”
It’s worth mentioning that canakinumab has notable side effects, such as heightened risks for infection and sepsis, as Dr. Peter Mazzone from the Cleveland Clinic pointed out. Even within a specific group, it might be too hazardous for the potential benefits to justify its use. He suggested that there might be alternative medications targeting the same pathway that could be safer.
Moreover, the protein signature could enhance the identification of individuals most likely to benefit from lung cancer screenings utilizing low-dose CT scans. Present recommendations in the U.S. suggest annual scans for those aged 50 to 80 with a 20 pack-year smoking history and who currently smoke or have quit within the past 15 years.
However, many eligible patients don’t follow through with scans, as Dr. Mazzone observed. If doctors had a blood test to pinpoint those most at risk, it could encourage more people to get checked. Additionally, this blood test could identify individuals who might not meet current eligibility but are still at increased risk.
There’s a particularly pressing need to enhance detection of lung cancer in non-smokers, as Dr. Mazzone noted. The recent study implies that certain elements of the protein signature might assist in pinpointing non-smokers at greater risk for lung cancer, but further research is necessary to confirm this potential.
