Identifying genetic mutations in lung cancer has allowed researchers to develop treatments that target specific biomarkers over the past 20 years, but more research is needed to further the space.
The use of biomarkers in lung cancer has grown by leaps and bounds from where it was 20 years ago.
Back then, not much was known about the molecular basis of lung cancer, and thus there were no targeted agents with which to treat it. Today, biomarkers are a mainstay in determining the most beneficial approach.
In honor of its 20th anniversary, CURE® spoke with Joann Sweasy, director of the University of Arizona Cancer Center in Tucson, to learn more about how far the study of biomarkers has advanced and where it may be headed.
“We’ve come amazingly far,” she said. “It’s a game changer what we’re doing right now. We are so ahead of where we were in 2002, it’s amazing.”
Technically, biomarkers are mutations — similar to typos — in DNA. These typos can be big, small or even a rearrange- ment in the DNA sequence.
“The mutation, they profile a number of different genes,” Sweasy explained. “These genes encode proteins, and essentially, what happens is (that) these mutant or altered proteins ... make every single cell survive, and the cancer cells survive. That’s what they’re about, promoting survival.”
Testing for biomarkers is performed primarily via biopsy, although it can also be done by bronchoscopy (a procedure that allows doctors to look at a patient’s airways and lungs) or by testing sputum (saliva and mucus from the respiratory tract).
Although it is standard at National Cancer Institute-designated centers, patients should inquire about the testing regardless of where they receive their diagnosis and treatment, Sweasy advised.
“I would ask, ‘How are you really going to diagnose (lung cancer)? And are you going to profile the genomics and look for genetic changes in my cancer?’” Sweasy explained.
Progress has been made because researchers have come to understand the three-dimensional structure of the proteins involved. By comparing normal and mutant proteins, they can see where the change has occurred and use that information to design drugs that target the mutation, Sweasy said.
The challenge now is to understand why tumors become resistant to targeted therapies over time.
“The goal of the cancer (cells) is to survive,” Sweasy said. “As that cancer proliferates and proliferates, more and more mutations are arising, so that’s where the resistance comes in. A targeted therapy is provided; you can be on that therapy and doing well for quite a while and then, all of a sudden, the tumor becomes resistant. That’s where we really need to get better these days.”
In addition, more research is required to detect biomarkers for other types of cancer.
Further investigation is needed to determine which biomarkers are actionable for small cell lung cancer, which is often associated with cigarette smoking. Smoke itself can cause mutations in the tumor.
“People with lung tumors with lots and lots of mutations generally respond to immunotherapy, but not all the time,” Sweasy said. “And some people who don’t have high levels of mutations in their tumors respond. We need to figure that out, too.”
Although biomarker testing is becoming a bigger part of a patient’s care journey, not every patient has access to these tests. Social determinants of health and rural disparities make it more difficult for certain individuals to access these tests, and insurance does not cover them in all circumstances, Sweasy noted.
Despite unmet needs in this area, the progress that has been made offers patients more effective treatments and allows them to learn more about the disease.
“I think the field continues to grow,” Sweasy said. “There’s real potential to be able to manage lung cancer in the future with fewer deaths than we have now, even though we are doing much better than we did back
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