Northwestern researchers make breakthrough discovery in genetic factors of small-cell lung cancer

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Daily file illustration by Catherine Buchaniec

Northwestern researchers identified the POU2AF2 gene that is critical to the formation of the deadly small-cell lung cancer.

Caryl Shepard, Reporter

Feinberg researchers recently discovered a link between a previously unknown gene and the formation of a rare and aggressive lung cancer. 

Small-cell lung cancer, the disease linked to the gene, typically results in rapid tumor growth, early metastasis and resistance to therapeutic treatments. The researchers began studying small-cell lung cancer and its factors in 2020 and released their findings in Science Advances in October. 

Co-first author and Feinberg Prof. Lu Wang, said the team chose specifically to focus on lung cancer as the most common cause of cancer death in the U.S. 

“We focus on small-cell lung cancer because it’s a more malignant subtype of lung cancer,” Wang said. “The five-year survival rate for small-cell lung cancer is about 7%.” 

Small-cell lung cancer has remained relatively unstudied in past years due to a lack of technology, co-first author and Feinberg research technician III Aileen Szczepanski said.

However, the expanded use of CRISPR, which allows scientists to edit genes, has helped researchers make strides toward a better understanding of these malignant cancers. 

“In recent times, based on the advancements of genomics, we took the opportunity to investigate other essential factors that are important to the cell viability of these specific subtypes,” Szczepanski said.

After studying the four gene subtypes relevant to small-cell lung cancer, NU researchers identified one most likely to cause the disease: the P subtype.

Upon studying the P subtype, the research team discovered the previously unstudied “C11orf53” gene. The gene plays a key role in the production of small-cell lung cancer cells, Wang said. 

Researchers tested whether eliminating the C11orf53 gene would reduce tumor growth and therefore slow the growth of small-cell lung cancer, Szczepanski said. They used CRISPR technology to “knock out” the C11orf53 gene and determine if it would reduce the spread of tumor growth in embryonic cells. Ultimately, Szczepanski said, they determined the removal of the C11orf53 gene increased cell death and slowed tumor growth. 

Study co-author and Feinberg Prof. Rintaro Hashizume said once the researchers found this approach successful in embryonic cells, they used the same in live mice to similar results.

“If you (eliminate) C11orf53 in mouse tumors, the tumor is totally reduced. It’s pretty much effective,” Hashizume said. 

Following this discovery, researchers renamed the C11orf53 gene based on its location and function as “POU Class 2 Homeobox Associating Factor 2.” 

Wang said the gene is critical to the tumor cells’ growth. 

“Based on our analysis, we found this is the central pathway for this cancer,” he said. 

Following this discovery, Szczepanski said she hopes to identify more factors linked to the onset of small-cell lung cancer.

Researchers hope the identification of all factors linked to the cancer will lead to more specific and individualized treatment plans for small-cell lung cancer patients, she added. 

Wang said the team is currently collaborating with pharmaceutical companies to devise drugs that will eliminate the POU2AF2 gene in humans, though the researchers must first garner financial support. 

“We have to talk to people and convince them to collaborate,” Wang said, “We also need to get some grant support to initiate the project because the drug discovery takes a long time and a lot of money.”

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Twitter: @carylshepard_

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