Assertive and coordinated action to implement cancer prevention was announced at the ESMO Congress 2022. It targets the estimated 40 percent of all cancers that are potentially preventable, said ESMO President Solange Peters, MD, PhD, Head of the Medical Oncology Service and Chair of Thoracic Oncology in the Department of Oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. She told a briefing that cancer clinicians needed to sustain quality of life by including prevention in their overall package of care to ensure quality of life. And on top of providing timely cancer therapy, they needed to play leading roles in improving the environment to help achieve prevention.
Peters said the Europe-wide prevention campaign now being implemented by ESMO combined existing well-publicized prevention methods-such as smoking cessation-but added new data-driven knowledge about molecular cancer initiation to prevent pre-cancers developing and promising new blood tests to improve early detection that could empower early interventions.
A key step forward for preventing malignant transformation was now possible thanks to research that appears to have pinpointed molecular progression from benign cellular DNA to malignancy, according to ESMO 2022 Scientific Co-Chair, Charles Swanton, FRCP, BSc, PhD, Professor and Senior Group Leader of the Francis Crick Institute and Consultant Oncologist at UCL Hospitals specializing in thoracic oncology.
"Ultimately, prevention is better than cure wherever possible," he told the conference. His group had investigated the relationship between air pollution and lung cancer in never smokers and had succeeded in throwing important new light on the already-known associations between air pollution and lung cancer.
"We've tried to establish how air pollution causes lung cancer," he told Oncology Times. "Through a series of steps involving animal models and human analyses, we've found that air pollution results in the release of a cytokine called interleukin-1[beta] from epithelial cells in the lung that generates and transforms cells with pre-existing mutations-that occur normally due to aging-into tumor cells."
His laboratory's expertise arrived at an opportune moment now that ESMO had committed to putting the spotlight on cancer prevention. In this new wave of efforts, the hope was to recruit both scientists and cancer clinicians into the front line to help implement cancer prevention. And the renewed enthusiasm for prevention had been data-driven, Swanton noted. "I think what's changed is our increasing understanding of the complexity of cancer, and our understanding that advanced metastatic disease is a formidable foe to cure."
He said there had been notable successes-as with checkpoint inhibitor therapies in diseases such as melanoma and late stages of other diseases. "But we are still only resulting in long-term remissions in 15-20 percent of our patients. If you are diagnosed with Stage IV disease, the vast majority of patients will succumb to the disease."
The growing realization among clinicians that the battle to improve survival outcomes in late-stage disease was huge had fueled renewed enthusiasm for prevention. This was just at a time when understanding the process of malignant transformation had improved enough to help make this possible and stop the disease evolving in the first place.
At ESMO, Swanton reported new epidemiological and laboratory-derived data that combined to help make prevention more achievable. "We looked at the UK biobank of 440,000 participants to see whether there was a correlation between rising PM 2.5 (particulate pollution matter that is 2.5 microns or smaller in size) pollution levels and incidence of various cancers."
His team found a correlation across seven cancer types-lung cancer, mesothelioma, head and neck cancers, oral pharyngeal cancers, lip cancer, anal cancer, some gastrointestinal cancers, and glioblastoma.
"We suspect it's driven by similar underlying mechanisms-where tissue inflammation, as a result of pollution, results in this transformation of cells into a cancer stem-cell-like property that enables a cell-if it harbors that mutation (which many of our normal tissue cells do in the body)-to then drive and initiate the cancer."
Swanton's team noted data from Taiwan and South Korea that mirrored the epidemiological evidence derived from the huge UK dataset: namely, that rising particulate (PM 2.5) levels correlated with increased incidence of EGFR-mediated lung cancer, a disease that classically occurred in never smokers.
The researchers had put their finger on a specific molecular initiation process. "That's why we're so excited. Really, for the first time, we've got our finger on the pulse, so to speak, of a new initiating process in cancer biology that begins to explain the interface and interaction between normal tissue clones that harbor cancer mutations as part of a process of aging, a natural process of aging, but won't cause cancer very frequently and will only do so in the context, potentially, of an environmental stimulus like pollution," Swanton explained. "But the implication was that there may be many other environmental carcinogens we don't yet understand that are doing similar things across other tissues in the body."
Although smoking was still the overwhelming risk for lung cancer, Swanton said that 5 times more people were exposed to excessive air pollution, so the overall numbers with cancers caused by pollution were considerable. "We have no choice about the air we breathe. So, there is a very significant risk at a population level," he said.
On top of this more refined knowledge of cancer initiation, Swanton's team had investigated mouse models that gave compelling evidence that the process could be avoided, not only by removing the pollution (which he said was a high priority) but also by treatments. His team used three different mouse models in which they stimulated the initiation of cancer mutations in normal epithelial cells. This had been in mice that generally grow tumors-especially adenomas-very slowly over time.
"We initiate the mutation much as we see in normal tissue of humans that you get with aging. And then we expose the mice to PM 2.5 levels-similar levels that you might be exposed to if you, say, lived in central London," he noted.
Swanton's research team then noted-over very short periods (typically about 10 weeks)-increases in the numbers of tumors in the mouse models, as well as increases in tumor grade and the relative numbers of carcinomas. And the mouse model research also opened the door to a possible drug intervention. The drug canakinumab had shown a dose-dependent reduction in lung cancer incidence.
"We didn't know how," Swanton stated. "And this begins to explain that possibly what it's doing is intervening in this inflammatory axis in response to air pollution and reducing that initiating, promoting step." When asked what could be done now and what should be done in the future, Swanton named two clear objectives. "First of all: A public mandate to reduce PM 2.5 levels-and obviously this link between climate health and human health. And secondly: We could use tools like this [research] to start to exploit other environmental carcinogens and understand their inflammatory axes that might be stimulating the expansion of these nascent clones."
Peter M. Goodwin is a contributing writer.