When Lung Cancer Strikes Without Warning

April 8, 2025 - by John Knox

Lung cancer is often associated with smoking – but what happens when it appears in people who’ve never smoked? A growing number of cases, particularly among non-smoking Asian women, are raising urgent questions about genetic risk factors, environmental triggers, and gaps in early detection. This troubling trend underscores a critical health disparity and the need for targeted research, clinical strategies, and culturally attuned public health responses.

That was the focus of the inaugural Stanford Lung Cancer Summit presented March 11-12, 2025 by the Stanford Center for Asian Health Research and Education (CARE).

While people with a history of smoking cigarettes make up the majority of those with lung cancer, up to one in five people with the disease never smoked. One such case is Bryant Lin, MD, the Taiwanese-American co-founder and co-director of CARE. 

As was described in a recent Scope article, during spring 2024 Lin was diagnosed with stage IV non-small cell cancer – typically called never-smoker lung cancer. He opened the program with intimate parts of his own story, sharing:

“My youngest child is in seventh grade. He's got five more years until he graduates from high school. My hope is that you all here today will come up with great discoveries and great advances – in not only basic science, but also in clinical care – and then I can live to see my youngest graduate.”

Lin, clinical professor of primary care and population health, co-chaired the summit with Heather Wakelee, MD, the Winston Chen and Phyllis Huang Professor and Chief of Oncology. In addition to Lin and Wakelee, the event featured many other Department of Medicine faculty. View the full agenda here.

Acknowledging the great progress that’s been made in recent years, Wakelee, a principal investigator in the CARE Lung Cancer Initiative, stressed the importance of harnessing that progress to make a bigger impact.

Contemplating Collective Science

The goal of the summit, she said, was to bring together members of the Stanford community to share and contemplate their collective science. The anticipated outcome was then to move forward in a clear direction and to develop stronger collaborations so that the Stanford lung cancer community can make the biggest impact.

During the two days, there was great emphasis on screening. Speakers also discussed different treatment modalities, from novel pulmonary technology to systemic treatments and even to different types of imaging. There were presentations on epidemiology, including ways of looking at large amounts of data and bringing it together and looking at environmental and other factors. While the conference shared some of what’s happening in labs at Stanford and elsewhere, that science was carried forward to be truly relevant to patient care.

The first day of the summit examined systemic treatments, epidemiology and population science, and the current state of developments for lung cancer in people who have never smoked.

What Lies Ahead

Day two looked at the future, beginning with a focus on the etiology of lung cancer and people without a smoking history. The day continued with a look into some science on novel detection monitoring and drug development.

Christina Curtis, PhD, discussed “Hereditary and Immune Determinants of Tumor Molecular Subtypes.” She addressed the timeline of drug development, noting that although her team’s initial focus was on breast cancer, the principles they applied – using machine learning to analyze high-dimensional data, including transcriptomes and genomes – led to the identification of 11 distinct breast cancer subgroups.  The team further demonstrated that these subgroups are not only prognostic but also predictive of which patients are likely to experience recurrence even two decades later.

“And this was all possible because we took very high dimensional data and asked what the underlying mutational processes were. And so by being unbiased and having global data, we could discover phenomenon that weren't previously described, and they're leading to new therapeutic approaches,” said the RZ Cao professor of Oncology, Genetics, and Biomedical Data Science and director of AI and Cancer Genomics at Stanford. 

While Curtis’s foundational research focused on breast cancer, the same data-driven approach can be applied to other cancers. This is especially important in lung cancer, where studies have shown a higher incidence among non-smoking Asian women compared to men. Since Curtis’s team primarily studied female patients, their methods are well-suited to uncovering hidden subtypes and mutational drivers in this population – offering potential for more precise, targeted therapies.

The Importance of Telomeres

Steven Artandi, MD, PhD, the Jerome and Daisy Low Gilbert Professor of Hematology and director of the Stanford Cancer Institute, addressed “Telomere Length as a Risk Factor for Non-Smokers’ Lung Cancer” by first explaining that a telomere is a protective cap at the end of a chromosome that prevents a signal for the cell to stop dividing. He reported that measuring telomere lengths could be informative in patients with never-smoker lung cancer, noting that long telomeres creates a very important risk factor for those patients.

Tushar Desai, MD, the Robert A. and Gertrude T. Hudson Professor of Pulmonary, Allergy and Critical Care Medicine, discussed “New Biological Insights into Never-Smoker Lung Cancer.” 

Working with Nick Juul, MD, a pulmonologist and instructor in his lab, Desai has been studying the differences in lung cells between mice with and without lung tumors. They used a method called methylation – which looks at chemical changes in DNA – to help them understand what’s happening in human lungs, too.

By isolating two specific types of lung cells from four different people and analyzing the DNA changes, they compared their results to a well-known classification from a 2023 Nature study. This allowed them to figure out which lung cells are most likely to turn into cancer in people who have never smoked. That’s important because knowing where these cancers start could lead to earlier detection and better, more personalized treatments for patients who don’t have the typical risk factors.

Later, responding to a question from an audience member, Desai said that his lab is sequencing blood samples that have been collected from their never-smoker population – which is highly enriched for Asian patients – to try to understand how long their telomeres are. 

“If that study is positive, then I think the next step would be a broader study that would regularly survey the people who are at the highest risk with a type of CT scan that uses lower amounts of radiation and is commonly used for lung cancer screening,” he said.

In a panel discussion including Curtis, Artandi, Desai and others, the importance of collecting more data was emphasized along with generating more models from mice to recapitulate aspects of the human disease.

Curtis said she was “quite inspired by thinking about all the connectivity on campus that is linking very nuanced molecular biology—like telomerase and the role it might play in tumor initiation and driving clinical outcomes, the different cell types, as well as the role of the immune system.”

Attendees Have Their Say

With an eye toward what’s in the offing, the summit concluded with questions and comments from attendees related to “Future Thinking and Developments for Lung Cancer in People Who Have Never Smoked.” 

That portion of the program emphasized the importance of early detection through enhanced screening, better data analysis (including the role of AI in mining data) and guidelines, and the need for collaborative research. Key points included the need for a registry to integrate electronic health records and AI for clinical samples as well as digital pathology for stratification. Proposals included creating an integrated database for tracking and studying lung nodules in Asian never smokers. Other opinions included the need for improved treatment modalities, increased engagement of primary care, and greater community outreach through social media.

Latha Palaniappan, MD, co-founder and co-director of CARE, and professor of cardiovascular medicine, pointed out that Asians make up 60% of the world, only 8% of those in genetic databases and only 10% of those in clinical trials. “So we have a long way to go to close that gap,” she said.

A common theme throughout the closing session was the need for increased funding – for research, screening, education, and treatment.

Wakelee said that “there's a real emphasis on what immune based therapies can do to treat lung cancer. We've made tremendous progress with those types of technologies – especially in people who develop lung cancer with a smoking history – where the biology is different and the disease is much more different from normal cells and therefore an easier target. We've really got a lot to do to understand how to bring that forward into people who develop lung cancer without a smoking history. That will be a major topic that we can be thinking about for a future symposium.” 

On the topic of screening, a visiting scholar from Australia noted that reducing the cost of CT scans will go far toward catching the disease earlier and increasing the patient’s chances of survival.

“You've got the best medicine in the world that is inaccessible to a larger number of your countrymen,” he said. “So the biggest question that seems to be holding things up is why do CTs cost so much? It's the gateway into diagnosis, management, screening and also peace of mind. I think you really need to have a very critical look at where the costs are. Is it the machine? Is it the infrastructure? Is it the radiologist reading it?”

Another participant said she wanted to “put a plug in for the collaborations with industry,” saying that to get academic ideas out to patients requires other partnerships.

A never-smoker lung cancer patient suggested that future summits involve representatives from the insurance community. “You can't advance the advocacy without advancing the payment systems in our process…because there is such a cost benefit for that commercial population that’s screened early,” she said.

Ultimately, the summit showcased a wide range of impactful ideas – from advancing early detection and enhancing community outreach to developing integrated databases for high-risk populations. But one of the most inspiring moments came from Dr. Artandi, who outlined a bold vision for the future of lung cancer research and care at Stanford – and offered a powerful reason for hope.