Research & Discovery

Q&A: What’s Going on With Lung Cancer Research?

In August, UVA Cancer Center became the first in Virginia to offer lung cancer patients the new drug tarlatamab, approved in May as immunotherapy to supercharge the body’s immune system to fight small-cell lung cancer in combination with chemotherapy.

The drug went through Phase 3 testing for the FDA at the Cancer Center and was one of several potential treatments investigated by the center’s researchers.

“We have a number of clinical trials at any given time for various subtypes and stages of the disease,” said Dr. Ryan Gentzler, a long-time thoracic medical oncologist at UVA Health treating patients with cancer in the chest, predominantly lung cancer.

“Some of those are early phase clinical trials developing brand-new drugs without a lot of track record, and some are later-phase trials, like in Phase 3 trials that have the potential to change the standard of care and get an FDA approval.”

UVA Today asked Gentzler about research involving lung cancer and its possible treatments.

Q. Can you contextualize lung cancer among other types of cancer?

A. Lung cancer is the most common cause of cancer in the United States and globally in terms of incidence. It’s second to breast cancer in women and prostate cancer in men, but the mortality rate is much higher. It remains the No. 1 cause of cancer-related deaths, and 80% of cases are typically attributed to tobacco exposure.

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Typically, heavier tobacco users are more likely to get lung cancer, but interestingly, about 20% of lung cancers happen in patients who have never smoked. We typically see this in younger individuals and women.

Fortunately, lung cancer rates have been dropping since smoking rates have started declining over the last couple of decades. We’ve also seen new lung cancer diagnoses dropping and survival rates improving due to advanced therapies.

Q. What other trends have we seen in the past decades?

A. One worrying trend is that lung cancer is on the rise within the group of patients who never smoked and tends to be on the rise faster in women. We don’t fully understand why that may be.

Other causes of lung cancer are well known, like radon gas exposure, which happens to be fairly prevalent in Appalachia. It’s harder to quantify and pin down, especially as society has become more mobile, and people are not living in one house their entire lives.

There’s also some research and interest in particulate-matter pollution and smaller fine particles in the air and their links to developing cancer. In large cities in China, for example, higher rates of lung cancer are potentially attributed to environmental exposure and air pollution.

Dr. Ryan Gentzler is a thoracic medical oncologist at UVA Health specialized in treating patients with lung cancer. (Photo by Matt Riley, University Communications)

Probably the biggest change in lung cancer in the last decade has been our ability to identify molecular subsets based on genetic profiles and create individual treatments based on the genetic makeup of a tumor. The other big thing is immunotherapy, which was initially used in patients with late-stage or Stage 4 cancer and is now being used in Stage 2 and 3 patients in addition to things like chemotherapy.

Lung cancer screening has been around for more than a decade now, so patients who are at higher risk of developing lung cancer are eligible. This is typically older individuals who have smoked for 15 years or longer. The original guidelines have been tweaked, and the ages for recommended screening have come down from 55 to 80 years to 50 to 80 years.

Q. As increased legalization of marijuana leads to more legal consumption, vapes maintain popularity and hookahs gain popularity, how will those activities affect lung cancer risks?

A. We really don’t know. Things like vaping are brand-new phenomena, and we don’t have decades of follow-up research to know if they increase the risk of lung cancer.

Vapes have been linked to other pulmonary diseases, including fibrosis. When inhaling substances, whether marijuana or vapes, there’s potential for lung injury and damage or at least irritation and inflammation.

Chronic use over many years could potentially lead to cancer development. It is probably a different mechanism than tobacco smoke, which is known to have multiple carcinogens in it. Marijuana itself is not a carcinogen.