Lung cancer remains the leading cause of cancer-related death in the United States. According to the NIH’s National Cancer Institute, there will be approximately 226,650 new cases and 124,730 deaths from the disease.

There are two main forms of lung cancer — small cell lung cancer and non-small cell lung cancer. Non-small cell lung cancer (NSCLC) is the more common form of the disease, accounting for over 85% of diagnosed cases. The most common subtypes of NSCLC are:

• squamous cell carcinoma, which begins in the thin, flat squamous cells.
• large cell carcinoma.
• adenocarcinoma.

Small cell lung cancer (SCLC) accounts for about 10% to 15% of diagnosed cases. SCLC is a fast-growing, aggressive form of lung cancer with poor outcomes. Unfortunately, most patients with SCLC are diagnosed with extensive stage disease, which means it has spread beyond the lung and the area between the lungs to other lymph nodes or other parts of the body.

Lung cancer is caused by certain changes to the way lung cells function, especially how they grow and divide into new cells. There are many risk factors for lung cancer, but many do not directly cause cancer. Instead, they increase the chance of DNA damage in cells that may lead to lung cancer.

Various factors can increase or decrease the risk of developing lung cancer. Anything that increases your chance of developing a disease is known as a risk factor, and anything that decreases your chance of developing a disease is known as a protective factor.

The following risk factors may increase the risk of lung cancer:

• Cigarette, cigar and pipe smoking: Tobacco use is the leading cause of lung cancer, responsible for the vast majority of cases — about 90% in men and 80% in women. All forms of smoking, including cigarettes, cigars, and pipes, significantly raise lung cancer risk. Research shows that “low tar” or “low nicotine” cigarettes do not reduce this risk. The likelihood of developing lung cancer increases with both the number of cigarettes smoked and the length of time a person has smoked, and smokers face roughly 20 times the risk compared to non-smokers.
• Secondhand smoke: Exposure to secondhand smoke also increases the risk of lung cancer. This smoke comes from burning tobacco products or from what smokers exhale. People who breathe in secondhand smoke are exposed to the same cancer-causing chemicals as smokers, though at lower levels.
• Family history: A family history of lung cancer can increase a person’s risk, potentially doubling the likelihood of developing the disease. However, it’s difficult to determine whether this higher risk is due to inherited factors or shared exposure to cigarette smoke, since smoking and secondhand smoke often occur within families.
• HIV infection: HIV infection is associated with a higher risk of lung cancer, with people living with HIV having more than double the risk of those without the virus. However, because smoking is more common among individuals with HIV, it’s unclear how much of this increased risk is due to the infection itself versus tobacco exposure.
• Environmental risk factors:
  • Radiation exposure is a known risk factor for lung cancer, with sources including atomic bomb radiation, radiation therapy, certain imaging tests, and radon gas. Individuals exposed to atomic bomb radiation or high doses of chest radiation therapy face an increased risk, especially smokers. Imaging tests like CT scans also involve radiation, though low-dose scans used for lung cancer screening reduce this risk. Radon, a naturally occurring radioactive gas that can accumulate in homes, is another major contributor. High indoor radon levels raise lung cancer risk, particularly for smokers, and are linked to about 26% of lung cancer deaths among people who have never smoked.
  • Workplace exposure to substances such as asbestos, arsenic, chromium, nickel, beryllium, cadmium, and tar or soot also raises lung cancer risk, even among nonsmokers, with risk increasing alongside exposure levels and smoking.
  • Additionally, living in areas with high air pollution has been shown to further increase lung cancer risk.
• Beta carotene supplements in heavy smokers: Taking beta carotene supplements can raise the risk of lung cancer, especially for people who smoke a pack or more a day. The risk is even higher for smokers who also drink alcohol daily.

Knowing what raises your lung cancer risk is important but so is understanding what you can do next. Screening tests look for cancer before symptoms appear. Researchers study these tests to find those that offer the most benefit with the fewest risks, and to determine whether finding cancer early helps people live longer. For many cancers, outcomes improve when the disease is detected and treated early.

Three screening methods have been evaluated for their ability to reduce lung cancer deaths:

• Low-dose CT (LDCT)
• Chest x-ray
• Sputum cytology

Among these, annual LDCT screening has been shown to lower the risk of dying from lung cancer in heavy smokers. In a large study of adults ages 55 – 74 with a long smoking history, LDCT detected early-stage lung cancer more effectively than chest x-rays and decreased the risk of dying from lung cancer. However, LDCT screening can still have downsides, such as false alarms or finding cancers that might never cause problems.

The Lung Cancer Screening Program at the University of Cincinnati Cancer Center was the first of its kind in Greater Cincinnati and has been designated a Lung Cancer Screening Center of Excellence by the Lung Cancer Alliance. The program brings together specialists across every aspect of lung cancer care, forming the region’s only comprehensive team dedicated solely to the disease. With deep clinical expertise and a strong foundation in scientific discovery, the program provides patients with the most advanced care options available. To schedule a screening, call 513-584-LUNG (5864) and select option 1.

In the Lab

Researchers are studying a small molecule called iMDK, which can trigger cell death in certain lung cancer cells with KRAS mutations — a common and difficult-to-treat genetic change. Until now, the way iMDK caused cancer cells to die wasn’t clear, and its oily, water-insoluble nature made it hard to use in potential treatments.

New research shows that iMDK activates a specific stress-related pathway in cancer cells called the ATF3-CHOP pathway, which leads to apoptosis (cell death). When this pathway was removed using gene-editing tools, iMDK no longer worked — confirming its importance. The molecule also showed activity in KRAS-mutant cells that were either sensitive or resistant to the targeted drug sotorasib.

To make iMDK usable in the body, scientists packaged it into special lipid nanoparticles that can be mixed with water. One of these formulations successfully delivered iMDK to cancer cells and reduced tumor growth in mice, without causing liver damage.

These findings suggest that a water-soluble nanoparticle version of iMDK could one day offer a new treatment option for certain KRAS-mutant lung cancers that rely on the ATF3 pathway.

[headshot] Donglu Shi, PhD Associate Member, Signaling Networks & Metabolic Pathways Research Program University of Cincinnati Cancer Center

Professor, Department of Materials Science & Engineering University of Cincinnati College of Engineering & Applied Science

[headshot] Yutaka Maeda, DVM, PhD Member, Pediatric Oncology Research Program University of Cincinnati Cancer Center

Assistant Professor, Department of Pediatrics University of Cincinnati College of Medicine

In the Community

On Saturday, November 8th, the University of Cincinnati Cancer Center’s Office of Community Outreach & Engagement partnered with Cops Caring for Cops, UC Health and the UC chapter of the American Lung Cancer Screening Initiative (ALCSI) to host a community event in recognition of National Lung Cancer Screening Day. The event was created specifically to meet first responders where they are by bringing essential cancer-related education and screening resources directly to those who face higher occupational risks. Cops Caring for Cops — a nonprofit dedicated to assisting Cincinnati Police Department members and their families affected by cancer — helped connect the Cancer Center with this high-need population. Attendees were able to complete the Cancer Center’s lung cancer pre-screening through UC’s ALCSI chapter, and UC Health provided additional wellness checks, including blood pressure and glucose screenings.