NU researchers identify a genome to help treat small-cell lung cancer

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

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

Co-first author and Feinberg Professor Lu Wang, He said the team specifically chose to focus on lung cancer as the most common cause of cancer death in the United States

“We are focusing on small-cell lung cancer because it is 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 III research technician Aileen Szczepanski He said.

However, the expanded use of CRISPR, which allows scientists to modify genes, has helped researchers take steps toward a better understanding of these malignant cancers.

“Recently, based on advances in genomics, we have taken the opportunity to investigate other underlying factors that are important for the survival of this specific subspecies,” He said.

After studying the four subtypes of genes involved in small-cell lung cancer, NU researchers identified one most likely to cause the disease: the P.

In studying the P subtype, the research team discovered what had not been studied previously Gene “C11orf53”. Wang said the gene plays a key role in the production of small-cell lung cancer cells.

The researchers tested whether knocking out the C11orf53 gene would reduce tumor growth and thus slow the growth of small-cell lung cancer, Szczepinski said. They used CRISPR technology to “knock out” the C11orf53 gene and determine if it would reduce tumor spread in embryonic cells. Ultimately, they determined, Szczepinski said, removing the C11orf53 gene increased cell death and slowed tumor growth.

Once the researchers found this approach successful in embryonic cells, they used the same thing in live mice to get similar results, said study co-author and Professor Rintaro Hashizume.

“If you (remove) C11orf53 in the tumors of the mice, the tumor is completely reduced. It’s pretty effective,” Hashizume said.

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

Wang said the gene is important for the growth of cancer cells.

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

After this discovery, Szczepinski said she hopes to identify more factors associated with the onset of small-cell lung cancer.

She added that the researchers hope that identifying all the factors associated with cancer will lead to more specific and individualized treatment plans for patients with small cell lung cancer.

The team is currently collaborating with pharmaceutical companies to create drugs that knock out the POU2AF2 gene in humans, Wang said, though the researchers must first obtain financial support.

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

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