Experimental drug combo inhibits growth of lethal lung cancer in mice
Small cell lung cancer (SCLC) is one of the deadliest forms of the disease, but now scientists may have a promising new avenue for treatment. By combining a new drug with an older drug, the team found that they could inhibit tumor growth in mice.
Occurring most commonly in smokers, small cell lung cancer is an aggressive form of the disease with a low survival rate. While chemotherapy is initially effective, cancer can quickly develop resistance to drugs, leading to recurrence and progression of the disease.
For the new study, researchers from the University of Washington, Grenoble Alps University and the University of Texas in St. Louis examined how SCLC cells resist damage from chemotherapy, and how it can be countered.
In previous work, the scientists found that a protein called RNF113A was implicated in cancer cells’ ability to repair alkylation damage, which is the mode of attack for common chemotherapy drugs. Upon closer inspection, the team found that RNF113A is regulated by another protein, SMYD3, which is expressed in high amounts in SCLC cells and other cancers. In particular, higher levels of SMYD3 are associated with more aggressive cancers and stronger drug resistance.
With this new target in their sight, the scientists investigated whether blocking SMYD3 could improve the effects of chemotherapy drugs. The team grafted human SCLC cells into mice, and waited until tumors grew in their lungs. Then, they treated some of the mice with a drug called cyclophosphamide, some with an SMYD3 inhibitor, some with both, and some without either.
In mice given chemotherapy alone, tumors stopped growing for about two weeks before starting to regress, indicating that drug resistance had built up. But in mice given both cyclophosphamide and an SMYD3 inhibitor, tumors stopped growing for the entire duration of the experiment. Interestingly, the treatment also worked on tumors grown from a human patient whose cancer had already developed resistance to chemotherapy drugs.
Because of its stronger side effects than platinum-based chemotherapy agents, cyclophosphamide has fallen out of favor somewhat in recent decades, but the new study may mean it’s worth the dusting. The team hopes the research could lead to new treatments for an aggressive form of cancer for which there are currently few options.
“We are in talks with several other groups about starting a phase 1 clinical trial as soon as possible,” said study co-senior author Nima Mosamparast. “People with small cell lung cancer are in dire need of better treatment, and I’m very excited about the possibilities here.”
The research was published in the journal cancer discovery,
Source: Washington University in St. Louis
