Purine Inhibitor Suppresses Tumor Growth, Increases Lifespan in Mice with SCLC

Patients with small cell lung cancer (SCLC) suffer from an aggressive and deadly form of the disease, with only 5% of patients surviving 5 years after their initial diagnosis. Although treatment options have been incredibly limited, a new study suggests a way to potentially treat SCLC with existing therapies.

Researchers believe understanding the metabolism of SCLC and identifying its pathways will help find new therapies. The metabolic pathways of cancer cells are reprogrammed to facilitate rapid spread throughout the body. Gene mutations in certain cancer cells can result in a dependence on a specific metabolic pathway, according to a study published in Cell Metabolism.

“SCLC metabolism has not previously been studied in-depth,” Ralph DeBerardinis, MD, PhD, lead study author, said in a press release. “If we identify the metabolic pathways SCLC uses to grow and spread, then maybe we can find drugs to inhibit them. This could effectively cut off the fuel supply to these tumors.”

The researchers analyzed the gene expression and metabolism of human SCLC tumor cells from 25 patients. Two types of SCLC were recognized by the levels of the oncogenes MYC and ASCL1, 2 genes that promote cancer cell growth and tumor formation, according to the study.

MYC was found to be involved in the synthesis of purine molecules, which are necessary for DNA and RNA production, and therefore cell growth and division. The researchers found that SCLC cancer cells expressing MYC were dependent on a particular purine molecule called guanosine. This finding is significant because guanosine inhibitors have been safely and effectively used as a treatment in other diseases, the researchers noted.

“We were excited to discover that purine synthesis was so important for this subset of SCLC cells. There are already safe and effective inhibitors of guanosine synthesis used in patients for other diseases besides cancer,” Fang Huang, MD, PhD, said in the press release. “Our findings suggested that mice with MYC-expressing SCLC might benefit from treatment with drugs that inhibit purine synthesis.”

The researchers tested the efficacy of purine inhibitor mizoribine in mice with different models of SCLC, and found a suppression of tumor growth and a significantly increased life span in mice with MYC expressions.

“Our findings suggest purine synthesis inhibitors could be effective in SCLC patients whose tumors have high levels of MYC. If we are right, this could quickly provide a new treatment for this disease, which has few options at present,” Dr. DeBerardinis concluded in the press release.

Reference

Researchers discover new vulnerability in deadly form of lung cancer [news release]. UT Southwestern Medical Center’s website. https://www.utsouthwestern.edu/newsroom/articles/year-2018/lung-cancer-cri.html. Accessed July 6, 2018.