Small cell lung cancer (SCLC) accounts for about 15% of all lung cancers and is found most often in people with a history of tobacco exposure. Patients with late-stage SCLC often respond so well to initial treatments that the cancer usually regresses and can even become undetectable in some cases. Unfortunately, in the vast majority of these cases, the cancer soon returns aggressively and is then resistant to treatment.
Jonathan Lehman, MD, PhD, is a medical oncologist and lung cancer researcher at Vanderbilt University Medical Center who has seen firsthand the limited treatments available for patients with late-stage SCLC. “We are due for some breakthroughs in small cell lung cancer,” he says.
Dr. Lehman spends approximately 25% of his time treating patients and 75% of his time conducting critical SCLC research. “Each aspect of my work benefits the other,” he explains. “I draw the motivation for my research from the patients I see. And by staying on the cutting-edge of research, I can offer my patients the most up-to-date information and resources.”
Dr. Lehman wants to understand the cancer recurrence seen in SCLC patients. He hypothesizes that although the cancer may appear to have completely regressed after treatment, it is likely that the cancer isn’t completely gone. “It is possible that there is a small population of cancer cells that survive or are resistant to several rounds of treatment. Perhaps these cells eventually begin to grow again and cause the cancer recurrence or are vital to the resistance to treatment.”
Currently, researchers typically study SCLC tissue in batches. They mix the cells together, open them up, and study the proteins, DNA, and other components that they discover in the mixture. However, Dr. Lehman and his mentor Pierre Massion, MD, who is also a member of LUNGevity’s Scientific Advisory Board, realized that this approach could miss identifying any rare populations of cells that could be contributing to recurrence or drug resistance.
“I sometimes describe it as a smoothie with different fruits mixed together,” explains Dr. Lehman. “Currently we are finding the most abundant fruits, say the mango chunks and the banana…We need a new approach to help us find the single blueberry in the mixture.”
Dr. Lehman and his team of collaborators worked with a new technology, called mass cytometry, that studies individual cells from a tissue sample and uses antibodies linked to rare metals to provide high-resolution analysis of cellular components. The team showed that this approach can successfully be used to study individual cells of SCLC tissue samples.
In order to utilize this technology and deepen our understanding of SCLC, Dr. Lehman applied for and was granted a three-year Career Development Award from LUNGevity Foundation in 2016 to help him establish his research laboratory with a focus on lung cancer. “I interviewed 13 people before I found the right laboratory technician,” notes Dr. Lehman. “His work has been phenomenal. He has been vital to the progress we have made in a relatively short amount of time. The LUNGevity grant helped me hire him and enabled us to lay a solid research foundation. Now, I am able to apply for larger federal research grants to continue my work.”
The exciting research in Dr. Lehman’s laboratory includes experiments using mass cytometry to study SCLC cells before chemotherapy and after cancer recurrence. By comparing the cellular components found in individual cells and identifying new or rare groups of cells, Dr. Lehman’s team is working to identify changes in the tumor cell groups that cause the cancer to become resistant to treatment. “If we can find the changes that cause the drug resistance, we can figure out a way to target these resistance pathways and improve outcomes for SCLC patients,” says Dr. Lehman.
Dr. Lehman and his team are starting to see results. Though they are only two years into the grant from LUNGevity, they have already identified rare yet promising populations of cells in SCLC that could improve our understanding of drug resistance and cancer recurrence.
“Of course, more studies are needed here,” notes Dr. Lehman. “But we are just getting started. And I truly believe that we are closer than ever to making a real impact on the lives of patients facing a SCLC diagnosis.”
Juhi Kunde, MA, is a science writer for LUNGevity.