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 gene-related disease, often 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 published their findings in Science Advances in October.
Co-first author and Feinberg Prof. Lu Wang, said the team chose to focus specifically on lung cancer as the most common cause of cancer death in the US.
“We focused 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 around 7%.”
Small cell lung cancer has remained relatively unstudied in recent years due to lack of technology, co-senior author and Feinberg III research technician Aileen Szczepanski said.
However, the expanded use of CRISPR, which allows scientists to edit genes, has helped researchers move toward a better understanding of these malignant cancers.
“In recent times, based on advances in genomics, we took the opportunity to investigate other essential factors that are important for cell viability of these specific subtypes”, Szczepanski said.
After studying the four gene subtypes relevant to small cell lung cancer, the NU researchers identified one most likely to cause the disease: the P subtype.
By studying the P subtype, the research team discovered the previously unstudied Gene “C11orf53”. The gene plays a key role in the production of small cell lung cancer cells, Wang said.
The researchers tested whether knocking out the C11orf53 gene would reduce tumor growth and thus 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 that deletion of the C11orf53 gene increased cell death and slowed tumor growth.
Study co-author and Feinberg professor Rintaro Hashizume said that once the researchers found this approach successful in embryonic cells, they used it in live mice with similar results.
“If you (knock out) C11orf53 in mouse tumors, the tumor shrinks completely. It is quite effective,” Hashizume said.
Following this discovery, the researchers renamed the C11orf53 gene based on its location and function as “POU class 2 homeobox association factor 2.”
Wang said the gene is essential for the growth of tumor cells.
“Based on our analysis, we found that this is the central pathway for this cancer,” he said.
Following this discovery, Szczepanski said he hopes to identify more factors associated with the development of small cell lung cancer.
Researchers hope that identification of all cancer-related factors will lead to more specific and individualized treatment plans for patients with small cell lung cancer, he added.
Wang said the team is currently collaborating with pharmaceutical companies to design drugs that knock out the POU2AF2 gene in humans, though the researchers must first obtain financial support.
“We have to talk to people and convince them to collaborate,” Wang said, “we also need to get some grant to start the project because drug discovery takes a lot of time and money.”
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