Stopping Lung Cancer Before It Gets Going

March 7, 2016 | Written By: Upal Basu Roy, MPH, PhD | Source: LUNGevity

“The LUNGevity award provided me the resources to study premalignant lung cells—a stage in which normal lung cells have changed, but not yet completely into cancer cells. This is an extremely important area of cancer research for lung cancer as well as for other types of cancers. Studying premalignant cells provides us a unique window to understand the early stages of lung cancer—before the lung cells acquire the mutations in DNA that allow them to become cancer cells. Such studies allow us not only to develop biomarkers for early disease detection, but also to identify new targets for cancer treatment and prevention.” —Jennifer Beane, PhD

Cancer develops in a sequenced manner. Patches of lung cells gain the ability to multiply faster than their neighboring normal cells by acquiring mutations. These patches of cells are called “premalignant lesions” (PMLs). Some of these lesions may eventually become cancer. LUNGevity Career Development Awardee Dr. Jennifer Beane from Boston University has been studying the differences between PMLs and normal lung cells in order to develop predictive biomarkers to determine who might be at high risk for developing lung cancer and thus need further screening. I sat down with her to discuss her work.

LUNGevity: What is the focus of your LUNGevity award?

Jennifer Beane: I was always interested in developing tools to catch lung cancer early. As a PhD student, I studied how a special type of cell that lines the respiratory tract, also known as a respiratory epithelial cell, reacts to cancer-causing substances, or carcinogens. As you know, exposure to cigarette smoke is a known risk factor for lung cancer. My project focused on understanding how smoking injures respiratory epithelial cells. I helped develop a biomarker that could identify whether or not epithelial cells were from a person with lung cancer. While this was exciting, I became interested in understanding earlier stages of the disease—what are the changes that are happening in normal lung cells before they become cancerous? I wanted to learn more about this stage because it represents a unique opportunity for therapeutic intervention. That’s how I got interested in the study of premalignant lesions, or PMLs. These patches of cells in the respiratory tract are not like normal lung cells. They have a life of their own. They can progress quickly to become cancer, go away, or stay stable for years without causing any trouble. What determines whether these lesions become cancerous? Does how the cells respond to injury from carcinogens decide whether a PML becomes cancerous? These questions keep me awake at night and are the focus of my LUNGevity grant. With this grant, I am studying RNA molecules from normal lung cells and PML cells to understand how they work and then develop a biomarker that can identify the presence of PML cells and predict which PMLs will progress to full-blown cancer.

L: What are some of the major findings of your project?

JB:  Cells in our body use different metabolic pathways to make energy. While studying PMLs, we stumbled upon something unusual: PMLs and normal lung cells use different pathways to produce energy and survive. We can capture this difference and other changes in a biomarker signature that I developed. This is helpful because our technology is easily adaptable to a clinical setting. In the clinic, respiratory cells are collected during a procedure called bronchoscopy. These cells can then be tested for the presence of a precancer signature. Veracyte, a biotechnology company, has already developed a test known as PerceptaTM to decide whether a person needs further invasive tests to diagnose lung cancer. The idea behind the research on PMLs is to develop similar such tests that can identify people with PMLs that will progress to cancer. People with these types of PMLs would need more aggressive screening or may benefit from cancer prevention drugs. This is a very exciting time in early detection research because there are so many new technologies.

L: How is your project changing our understanding of chemoprevention for lung cancer?

JB: Our research has opened up the exciting possibility of developing drugs that stop lesions from progressing to full-blown lung cancer, a concept known as chemoprevention. For example, taking an aspirin can protect you from developing colon cancer if you belong to the high-risk group. However, we have not had much success with chemoprevention in lung cancer. This might have been because we were not selecting the right group of patients. Now that we have a biomarker signature for PML, we can use it to select patients who might benefit from chemoprevention and treat them with a drug that stops cancer from developing. We are not there yet, but I cannot help but feel excited—we might someday have drugs that stop lung cancer from developing altogether.

(This is the first blog in a two-blog series of interviews with our amazing women scientists, who are contributing to major progress in lung cancer research. Stay tuned for the next blog, which will be focused on Targeted Therapy.)

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