Doctors and researchers at Memorial Sloan Kettering Cancer Center (MSK) have discovered a new and rare type of small cell lung cancer (SCLC).
What makes this discovery unique is that it affects younger people who have never smoked, which is very unusual for lung cancer.
Their findings, recently published in Cancer Discovery, reveal important details about this cancer, including genetic features that may help guide treatment decisions.
“This doesn’t happen every day,” said Dr. Natasha Rekhtman, the lead author of the study and a pathologist specializing in lung cancer at MSK.
“This new cancer type has unique characteristics and a different molecular mechanism compared to other types of small cell lung cancer.”
The study involved a large team of 42 doctors and researchers, combining expertise from different areas such as lung cancer treatment, cell and tissue pathology, tumor genetics, and computational analysis.
Together, they were able to identify this new subtype of lung cancer, which they’ve named “atypical small cell lung carcinoma.”
Small cell lung cancer is already rare, making up about 10% to 15% of all lung cancers. This new subtype is even rarer, as it accounts for just 3% of small cell lung cancer cases. Out of 600 patients with SCLC who were studied, only 20 were found to have this newly identified type.
Typically, small cell lung cancer is linked to heavy smoking and occurs when two important cancer-protecting genes, RB1 and TP53, stop working. However, patients with this new subtype still have functioning copies of these genes. Instead, their cancer cells often show signs of “chromothripsis,” a process where one or more chromosomes are shattered and rearranged in a chaotic way. This major event creates multiple genetic changes that lead to cancer.
Interestingly, this rare form of lung cancer develops from a transformation of less aggressive neuroendocrine tumors (also called pulmonary carcinoids) into a more aggressive cancer. Patients diagnosed with this subtype tend to be younger. In fact, the first patient with this type was just 19 years old and had never smoked—a stark contrast to the usual SCLC patients, who are often older and have a long history of smoking.
On average, patients diagnosed with atypical small cell lung carcinoma were 53 years old, which is considered young for lung cancer. Sixty-five percent of them had never smoked, and the remaining 35% had only a light history of smoking (less than 10 years).
The study also revealed that standard chemotherapy treatments, typically used for small cell lung cancer, may not work as well for this new subtype. Specifically, first-line platinum-based chemotherapies are less effective against atypical SCLC. However, the researchers found potential new treatment strategies that could be more beneficial.
This cancer has a unique origin story, explained Dr. Rekhtman. Instead of gradually accumulating mutations over time, this cancer likely begins with one catastrophic event that shatters the chromosomes, creating complex genetic changes. These changes include abnormal DNA structures called extrachromosomal circular DNA, which could be targeted by investigational drugs.
The discovery of this new subtype was sparked by the case of Khaliq Sanda, a 19-year-old who was diagnosed with small cell lung cancer while still a college sophomore at Duke University. Khaliq’s doctors were surprised by his case, as small cell lung cancer is almost always linked to heavy smoking, and he had never smoked.
Khaliq’s case led the research team to look for other young, non-smokers with small cell lung cancer. With the help of MSK’s advanced genetic testing, they were able to identify similar patients and find the genetic pattern that linked them together.
Despite his illness, Khaliq lived for five years after his diagnosis—an unusually long time for someone with small cell lung cancer. His courage and positivity left a lasting impact on those around him, and his family and friends raised more than $150,000 in his memory to support other young adults with cancer.
Khaliq also donated tissue for research after his death, which allowed MSK researchers to further study this rare cancer and pave the way for future treatments. “It was an amazing gift to society and science,” said Dr. Rekhtman.
Thanks to Khaliq’s decision and the expertise at MSK, this discovery may lead to better treatments for people diagnosed with this rare type of small cell lung cancer.
