New vulnerability found for virulent cancer

University researchers target genes of small, quickly spread cancers

More than 224,000 new lung cancer cases were opened in the United States in 2016 alone, and over 158,000 individuals died from lung cancer, according to the American Cancer Society website. Small cell lung cancer comprises 10 to 15 percent of all lung cancers.

Dr. Christopher Moskaluk, Department of Pathology chairman, said small cell cancers are characterized by small cell sizes and poor differentiation features.

“What a cell looks like and what functions it carries out is termed ‘differentiation,’” Moskaluk said in an email statement. “Most other lung cancers have larger cell bodies and show better differentiation features under the microscope.”

SCLC tends to grow and metastasize, or spread, faster than non-small cell lung cancer. Treatment regimens, chemotherapy and antibody treatments among them, vary compared to those designed for NSCLC.

Kwon-Sik Park, assistant professor of microbiology, immunology and cancer biology, is focusing on tumor-specific gene alterations as a potential opportunity for therapeutic targets.

“Treatments for SCLC have not significantly improved over the last four decades, and there are no currently approved targeted therapies,” Park said in an email statement. “It is therefore essential that the biology of major genes that drive SCLC be linked to novel therapeutic approaches.”

His lab’s research is funded by federal and foundational grants such as the National Institute of Health, the Department of Defense, the American Cancer Society and the Lung Cancer Foundation. Dong-Wook Kim and Kee-Beom Kim, post-doctoral students in his lab, and Colin Dunn and Ann Lee, undergraduate research assistants, researched and authored the lab’s most recent paper, published in the June 2016 edition of “Genes and Development,” “Genetic requirement for Myc1 and efficacy of RNA Pol I inhibition in mouse models of small cell lung cancer.”

The paper describes a role for L-Myc, a gene whose mutation has been found to lead to SCLC, in tumorigenesis and proposes that CX-5461, a drug causing RNA polymerase I inhibition, has the potential to attack the tumor and cause tumor inhibition. RNA polymerase I acts during transcription, which allows for gene expression via protein production.

This new vulnerability could lead to a potentially novel treatment for SCLC or, at the very least, lead to further investigation with similar therapeutic and research approaches.

The study, however, is still in its early stages and still has a way to go before becoming available as a potential treatment for the general SCLC populace in the United States.

“Our research provides a concept of targeting the oncogene-driven [caused by a person’s own genes] molecular changes for tumor intervention particularly when the oncogene itself is undruggable,” Park said. “More research needs to be done before applying this concept to treatment of lung cancer patients.”

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