While new discoveries in the realm of cancer research and treatment have become increasingly commonplace in this current era of innovation, the discovery of a new type of cancer is practically unheard of. But recently a team of doctors and researchers at Memorial Sloan Kettering (MSK) Cancer Center did just that, announcing that they have discovered a new, rare type of small cell lung cancer.
But perhaps equally surprising – this new type of small cell lung cancer primarily affects younger people who have never smoked.
A study published August 26 in Cancer Discovery involved 42 physicians across Memorial Sloan Kettering, including doctors who treat lung cancer, pathologists, and specialists in tumor genetics and computational analysis.
According to the American Cancer Society, small cell lung cancer (SCLC) is relatively rare, accounting for 10-15% of all lung cancers. This newly discovered subtype accounts for only a small fraction of those cases. Of the 600 patients with SCLC whose cancers were analyzed for the study, only 20 people (or 3%) were found to have the rare subtype.
SCLC is normally characterized by the “deactivation of two genes that protect against the development of cancer — RB1 and TP53.” According to MSK, patients with the new subtype – which researchers have named “atypical small cell lung carcinoma” – have “intact copies of those genes” and rather, “most carried a signature ‘shattering’ of one or more of the chromosomes in their cancer cells, an event known as chromothripsis.”
The researchers believe that the new subtype develops through a transformation of lower-grade neuroendocrine tumors – rare tumors that grow from neuroendocrine cells found in organs throughout the body – into more aggressive carcinomas.
“Patients who develop small cell lung cancer tend to be older and have a significant history of smoking,” said Charles Rudin, MD, PhD, a lung cancer specialist and the study’s senior author, in a news release. “The first patient we identified with atypical SCLC, and whose case led us to look for more, was just 19 years old and not a smoker.”
As it turned out, this was true for others with the subtype as well – the mean age at diagnosis was 53. In contrast, the average age for a lung cancer diagnosis is 70.
The study found that 65% of the patients with the new subtype were never smokers, and 35% reported a history of light smoking (less than 10 pack-years).
A pack-year is a measure used to determine how much a person has smoked over time. It is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked. For example, smoking one pack of cigarettes per day for one year is equal to one pack-year.
The study also found that “the unique genomic changes that give rise to atypical SCLC” make standard, platinum-based chemotherapies largely ineffective, suggesting some treatments that may be more impactful.
“We often talk about cancer as an ongoing buildup of mutations,” said Natasha Rekhtman, MD, PhD, an MSK pathologist specializing in lung cancer and the first author of the study. “But this cancer has a very different origin story. With chromothripsis, there’s one major catastrophic event that creates a Frankenstein out of the chromosome, rearranging things in a way that creates multiple gene aberrations, including amplification of certain cancer genes.”
The researchers concluded that patients with atypical SCLC may benefit from investigational drugs that target the disease’s unusual DNA structures, among other potential treatments.
