A group of doctors and researchers have discovered a new and rare form of small cell lung cancer that mainly affects younger individuals who do not smoke.
A group of doctors and researchers from Memorial Sloan Kettering Cancer Center (MSK) have found a novel and rare kind of small cell lung cancer that predominantly impacts young people who have never smoked.
Their research, which features an in-depth examination of the disease’s clinical and genetic characteristics, also emphasizes the weaknesses that could assist physicians in making improved treatment choices for affected patients.
“It’s not every day you come across a new subtype of cancer,” states Natasha Rekhtman, MD, PhD, an MSK pathologist who focuses on lung cancer and is the lead author of a paper released on August 26 in Cancer Discovery, presenting the team’s analysis. “This new cancer type exhibits unique clinical and pathological traits, alongside a distinct molecular mechanism.”
The research involved the collaboration of 42 physicians and specialists from MSK—ranging from lung cancer treatment practitioners to pathologists who diagnose based on cellular and tissue evaluation, and includes experts in tumor genetics and computational analysis.
“Grasping the concept of this new lung cancer subtype necessitated a diverse range of expertise from both laboratories and clinics,” mentions Charles Rudin, MD, PhD, a lung cancer expert and the study’s senior author.
Defining a New Lung Cancer Subtype: Atypical Small Cell Carcinoma
Small cell lung cancer (SCLC) itself is already uncommon, comprising about 10% to 15% of all lung cancer cases, according to the American Cancer Society. The newly identified subtype represents only a small portion of this. Among 600 patients with SCLC who were examined for the study, only 20 individuals (or 3%) were diagnosed with this rare subtype.
Typically, SCLC is marked by the inactivation of two essential genes that help prevent cancer development—RB1 and TP53—but individuals with the new subtype possess intact versions of these genes. Instead, most exhibited a unique “shattering” of one or more chromosomes in their cancer cells, a phenomenon known as chromothripsis.
This new subtype seems to develop from lower-grade neuroendocrine tumors (pulmonary carcinoids) transforming into more aggressive types of carcinomas. The research team has named this new category “atypical small cell lung carcinoma.”
“Typically, patients with small cell lung cancer are older with a significant smoking history,” Dr. Rudin, the Deputy Director of MSK’s Cancer Center, explains. “The first patient we uncovered with atypical SCLC, whose case prompted further investigation, was only 19 and had never smoked.”
This was also the case for the others with the subtype. The average diagnosis age was 53, which is considered relatively young; the average age for lung cancer diagnosis is 70. Of these patients, 65% had never smoked, while 35% had a history of minimal smoking (less than 10 pack-years).
Treating Atypical Small Cell Lung Carcinoma
The analysis revealed that the distinctive genomic alterations linked to atypical SCLC mean that conventional first-line treatments, such as platinum-based chemotherapy, are less effective. Their findings suggest alternative treatment strategies that may yield better results.
“Cancer is often perceived as cumulative mutations,” Dr. Rekhtman adds. “However, this cancer has a different narrative. With chromothripsis, a singular catastrophic event creates a jumble of the chromosome, leading to rearrangements that result in multiple gene abnormalities, including the amplification of certain cancer-related genes.”
This is why patients with atypical SCLC may benefit from experimental therapies targeting the unusual DNA formations resulting from chromothripsis, referred to as extrachromosomal circular DNA, according to the researchers.
