Lung cancer is the leading cause of cancer death in the United States for both men and women. According to the NIH’s National Cancer Institute, 234,580 patients will receive a diagnosis of lung cancer, and 125,070 patients will die of the disease in the United States this year.

There are two main categories of lung cancer: non-small cell lung cancer and small cell lung cancer. Non-small cell lung cancer (NSCLC) is the most common form of the disease, accounting for about 80% of diagnosed cases. The most common subtypes of NSCLC are:

• Squamous cell carcinoma, which begins in 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.

A risk factor is anything that increases the chance of getting a disease. Some risk factors for lung cancer, like smoking, can be changed. However, risk factors also include things you cannot change, like your genetics, age and family history. Learning about risk factors for lung cancer can help you make changes that might lower your risk.

Smoking tobacco now or in the past is the most important risk factor for lung cancer. Smoking cigarettes, pipes, vapes or cigars increases the risk of lung cancer. The earlier in life a person starts smoking, the more often a person smokes and the more years a person smokes, the greater the risk of lung cancer. Other risk factors for lung cancer include:

• Exposure to secondhand smoke.
• Exposure to asbestos, arsenic, chromium, beryllium, nickel, soot or tar.
• Exposure to radiation from:
  • Radiation therapy to the breast or chest.
  • Radon in the home or workplace.
  • Imaging tests, such as CT scans.
  • Atomic bomb radiation.
• Living where there is air pollution.
• A family history of lung cancer.
• Being infected with HIV.
• Taking beta carotene supplements and being a heavy smoker.
  

An Expert Perspective

“Lung cancer remains a disease that carries a significant mortality,” said Dr. Scaglioni. “However, innovative therapies, such as immunotherapy and targeted therapy, have improved survival. The five-year survival rate is approximately 25%, which is a 22% improvement over the last five years.”

[headshot] Pier Paolo Scaglioni, MD Associate Director, Translational Research Member, Signaling Networks & Metabolic Pathways Research Program University of Cincinnati Cancer Center

Pier Paolo Scaglioni, MD  Associate Director, Translational Research Member, Signaling Networks & Metabolic Pathways Research Program University of Cincinnati Cancer Center Director, Division of Hematology and Oncology Herbert F. Koch Professor of Medicine University of Cincinnati College of Medicine

Immunotherapy is a type of biological therapy that uses the body’s immune system to fight cancer. This cancer treatment works by activating the immune system and breaking the connection between checkpoint proteins. Immunotherapy can come in many forms, including:

• Targeted antibodies.
• Cancer vaccines.
• Adoptive cell transfer.
• Tumor-infecting viruses.
• Checkpoint inhibitors.
• Cytokines.
• Adjuvants.

“In the last five years, we have started using a combination of therapies to achieve the best long-term outcomes,” elaborated Dr. Van Haren. “Many patients who undergo surgery now receive chemotherapy, immunotherapy or targeted therapy either before or after surgery. Furthermore, the surgical techniques themselves have also improved, and therefore, improved outcomes for lung cancer patients.”

Robert M. Van Haren, MD, MSPH  Member, Experimental Therapeutics Research Program University of Cincinnati Cancer Center Program Director, Integrated Thoracic Surgery Residency Director, Cincinnati Research in Outcomes and Safety in Surgery University of Cincinnati Medical Center

Drs. Scaglioni and Van Haren also highlighted the promising future of lung cancer treatment and prevention, emphasizing advancements in personalized medicine and public health initiatives.

“I expect that we will continue to see developments in targeted therapies and immunotherapy as well as continued efforts aimed at smoking cessation and pollution reduction,” said Dr. Scaglioni.

“Additionally, I think we will continue to identify and expand the screening of lung cancer as there are many individuals who develop lung cancer who are not eligible for lung cancer screening,” expressed Dr. Van Haren. “I also think treatments will continue to improve as we discover new therapies that are used in combination with surgery to treat lung cancer.”

Preventing lung cancer and early detection are crucial in improving outcomes. Drs. Scaglioni and Van Haren advise steering clear of tobacco products and undergoing lung cancer screening if one has been exposed to tobacco.

“Avoid tobacco products,” stressed Dr. Scaglioni. “Avoiding tobacco products is extremely beneficial, but those who have been exposed to tobacco should definitely get screened for lung cancer.”

“I completely agree,” said Dr. Van Haren. “Lung cancer is curable, if it is diagnosed early!”

According to current guidelines, adults aged 50 to 80 with a 20-pack-year smoking history are advised to undergo annual lung cancer screening using a low-dose CT scan. This applies to individuals who currently smoke or quit within the last 15 years. A pack-year is calculated by multiplying the number of cigarette packs smoked daily by the number of years spent smoking. For example, someone who smoked one pack a day for 20 years would have a 20-pack-year history.

Updates on Research & Clinical Trials

Dr. Van Haren's research centers on enhancing outcomes for lung cancer patients undergoing surgery. He is particularly dedicated to advancing equitable lung cancer care and addressing disparities that impact racial minorities in the healthcare system.

“I am truly inspired by our patients with lung cancer, and my research is focused on improving outcomes for them,” shared Dr. Van Haren. “I have a special interest in improving the equity of lung cancer care and improving outcomes for racial minorities who experience healthcare disparities.”

The Disparities Associated with Decision to Undergo Oncologic Surgery: A Prospective Mixed-Methods Analysis study, led by Dr. Van Haren, aims to further elucidate the breakdown in the physician-patient relationship that leads to lower rates of guideline concordant care, surgical resections and survival among African American/Black patients.

This study, which was recently published in the Annals of Surgical Oncology, investigated provider-related barriers to care among patients with lung or gastrointestinal cancers undergoing surgical consultation, focusing on how communication, trust and cultural competency affect outcomes. Among 24 patients (63% White, 38% African American/Black), key social challenges included food insecurity (21%), unreliable transportation (17%) and housing instability (8%). Barriers such as lack of trust in physicians (13%), poor communication (8%) and insufficient cultural competency (13%) were also identified.

Qualitative analysis revealed five themes influencing surgery decisions: communication, trust, health literacy, patient fears and decision-making strategies. Notably, 21% of patients declined recommended surgery, with African American/Black patients, lower-income individuals, and those reporting poor patient-physician relationships significantly more likely to do so. The findings emphasize the need for interventions targeting these modifiable barriers to reduce racial disparities and improve surgical outcomes. 

“My colleagues and I have also done work to evaluate the role of air pollution on lung cancer outcomes,” Dr. Van Haren said. “We found that increased air pollution exposure was associated with worse overall survival.”

The Role of Environmental Exposures on Survival After Non-Small Cell Lung Cancer Resection study, which was recently published in the Annals of Thoracic Surgery Short Reports, examined the impact of environmental and social factors on survival after non-small cell lung cancer (NSCLC) resection. Data from 661 patients (2006–2021) were analyzed, linking residential PM2.5 exposure (fine particulate air pollution), greenness and deprivation index to patient outcomes.

Results showed that African American/Black patients experienced greater community deprivation than White patients, but there was no racial difference in PM2.5 exposure or survival. However, higher PM2.5 exposure independently predicted worse survival (hazard ratio 1.06, P = .003). The study concluded that air pollution had a stronger influence on survival than race or material deprivation. Reducing PM2.5 exposure could improve outcomes for NSCLC patients.

On a more molecular level, the Scaglioni Laboratory’s central goal is to identify cellular networks that are required for cancer maintenance using advanced lipidomics, mouse cancer models, cancer cell lines, small molecule inhibitors, RNAi and CRISPR technologies. Recently, members of the Scaglioni Laboratory have been investigating the connection between RAS mutation and ferroptosis susceptibility in cancer.

Ferroptosis is a newly recognized form of programmed cell death that could be used in cancer therapy. First described in the early 2000s, it is an iron-dependent process triggered by excessive lipid peroxidation (LPO), which damages cell membranes and leads to cell death. Since then, research has uncovered key pathways regulating ferroptosis and led to the development and repurposing of small molecules targeting this process.

However, much about ferroptosis remains unclear. Questions remain about whether specific oncogenes, cell types or tumor environments affect susceptibility to ferroptosis or whether certain ferroptosis-related genes could serve as universal cancer targets. While RAS-driven cancers were initially thought to be highly sensitive to ferroptosis inducers, later studies suggest that mutant RAS alone may not always trigger ferroptosis.

 In Our Community

In the University of Cincinnati Cancer Center’s ten-county catchment area, lung cancer is the most common cancer type with over 4,500 new cases each year in Cincinnati alone. Throughout the entire catchment area, the incident rate is 17% higher than the national average and the mortality rate is 21% higher than the national average. Additionally, there are also higher smoking rates throughout the catchment area and the state of Ohio in comparison to the national average. The Cancer Center’s Office of Community Outreach & Engagement (COE) works to establish, strengthen and leverage community partnerships throughout the region to better address the cancer-related challenges in the community, and over time, reduce the overall burden of cancer.

Furthermore, the Office of Community Outreach & Engagement (COE) works to bridge the gap between the Cancer Center and the community by sharing valuable insights and data, returning evidence-based research to the community and fostering education and advocacy opportunities. Recognizing the importance of early detection in cancer treatment, its educational efforts prioritize prevention, screening, early diagnosis and survivorship.

One such partnership is with the Lung Cancer Screening Program at UC Health. In fall of last year, the Lung Cancer Screening Program alongside the Office of Community Outreach & Engagement (COE), developed the lung cancer pre-screening – a series of questions to determine an individual’s need to undergo a lung cancer screening. To date, 106 pre-screenings have been administered in the community, resulting in 29 referrals to the Lung Cancer Screening Program and 57 referrals to the Smoking Cessation Program.

This pre-screening is utilized at numerous community events throughout the year with Cancer Center COE staff and volunteers present to not only administer the pre-screening but to also share more resources and information. This year, the COE Team has attended forty events highlighting lung cancer as a priority across the catchment area. This month, the Office of Community Outreach & Engagement (COE) attended the Aiken High School Health Fair on Tuesday, November 19th, which primarily focused on cancer risk factors, such as smoking tobacco products and the HPV vaccine. In partnership with UC Health and the 513 Relief Bus, the COE Team also attended the Ambrose Health Center Community Day on Saturday, November 23rd and administered lung cancer pre-screenings to eligible community members.