Study Identifies New Form of Small-Cell Lung Cancer

Researchers have recently discovered a new type of small-cell lung cancer (SCLC), and the discovery may pave the way for the development of personalized medicine in order to target this newly discovered form of the disease.

The discovery of this previously unnoticed form of the disease occurred as a result of a study of SCLC that applied domain-focused CRISPR screening, a gene-editing tool, to human cancer cell lines in order to identify the transcription factor, POU2F3, as a powerful dependency in a subset of SCLC.

“These data reveal POU2F3 as a cell identity determinant and a dependency in a tuft cell-like variant of SCLC, which may reflect a previously unrecognized cell of origin or a trans-differentiation event in this disease,” concluded the study.

Specifically, POU2F3 was expressed exclusively in the minority of SCLC tumors with low levels of neuroendocrine markers. The separate class of rare cells are called tuft cells, according to the study.

“We were using the CRISPR screen to discover new vulnerabilities in this disease that we didn’t know about before,” one of the authors, Christopher Vakoc, MD, PhD, a Cold Spring Harbor Laboratory Associate Professor, said in a statement. “The surprise is that in the process, we discovered a new form of lung cancer.”

Approximately 10% to 15% of all lung cancers are SCLC. Additionally, SCLC does not have a specific treatment that is known to be effective and the disease often spreads early on in patients. Treatments like chemotherapy, radiotherapy, and surgery typically allow only about 6% of patients to survive 5 years from the time of their diagnosis.

“In the past, we’ve lumped the different forms of SCLC together because they look similar on a microscope slide, but we now have some molecular tests that can easily discriminate these malignancies,” said postdoctoral investigator Yu-Han Huang, the first author on the new study. “Our findings suggest that we should be designing clinical studies for them separately, to find therapies that might cater to the different types of tumor.”

Currently, the researchers are looking for collaborators to continue their research and to conduct preclinical tests in mice in order to test compounds that specifically target POU2F3. In addition, the researchers intend to use the CRISPR-based stress test to look for variant types of pancreatic cancer and potentially develop more effective treatments.