A team of doctors and researchers at Memorial Sloan Kettering Cancer Center (MSK) have identified a new, rare type of small cell lung cancer that primarily affects younger people who have never smoked. Their findings, which include a detailed analysis of the clinical and genetic features of the disease, also highlight vulnerabilities that could help doctors make better treatment decisions for people diagnosed with it. The study brought together the expertise of 42 physicians and researchers across MSK, from the doctors who treat lung cancer and the pathologists who evaluate cells and tissues to specialists in tumor genetics and computational analysis. “Understanding this new type of lung cancer required a broad spectrum of expertise from the laboratory to the clinic,” says lung cancer specialist Charles Rudin, MD, PhD, the study’s senior author.
Small cell lung cancer (SCLC) is relatively rare, accounting for 10% to 15% of all lung cancers. The newly discovered subtype accounts for just a fraction of those cases, with only 20 out of 600 patients with SCLC found to have the rare subtype. These patients have intact copies of the genes that are usually deactivated in SCLC, and instead carry a signature “shattering” of one or more chromosomes in their cancer cells, known as chromothripsis. The new subtype appears to arise through a transformation of lower-grade neuroendocrine tumors into more aggressive carcinomas, and has been dubbed “atypical small cell lung carcinoma.” Patients with this subtype tend to be younger and have no history of smoking, with the average age at diagnosis being 53, as opposed to the average age of 70 for a lung cancer diagnosis.
The analysis found that the unique genomic changes that give rise to atypical SCLC mean that standard platinum-based chemotherapies do not work as well. Instead, the findings point toward some treatment strategies that may work better for this rare subtype of lung cancer. Patients with atypical SCLC may benefit from investigational drugs that target the unusual DNA structures resulting from chromothripsis, such as extrachromosomal circular DNA. This new understanding of the disease subtype may help doctors make more informed treatment decisions for patients with atypical SCLC, improving their chances of successful outcomes. The identification of this new subtype also sheds light on potential vulnerabilities that could be targeted for more effective treatment.
The discovery of this new subtype of lung cancer is significant as it provides insights into a rare form of the disease that affects younger individuals who have never smoked. The study’s findings shed light on the distinct clinical, pathological, and molecular features of atypical small cell lung carcinoma, allowing for better understanding and potentially more personalized treatment options. The multidisciplinary approach taken by the team of physicians and researchers at MSK highlights the importance of collaboration and expertise across various aspects of cancer research and treatment. The team’s work has the potential to impact the care of patients with this rare form of lung cancer, leading to more effective treatment strategies and improved outcomes.
The research on atypical small cell lung carcinoma emphasizes the importance of understanding the unique characteristics of different types of cancer, as they can have varying responses to standard treatments. The identification of this new subtype opens up new avenues for targeted therapies that may be more effective in treating patients with atypical SCLC. By focusing on the specific genomic changes and molecular mechanisms that drive this type of lung cancer, doctors and researchers can better tailor treatment approaches to individual patients, potentially improving survival rates and quality of life for those affected. The study’s findings offer hope for better outcomes for patients diagnosed with atypical small cell lung carcinoma, paving the way for more personalized and effective treatment strategies in the future.