“The problem is that these tumors respond to treatment initially, but then they come back. This has not changed for 30 years. These tumors are just massively resistant to just about everything. So what this study shows is that we can actually combine a new target with an old drug to reduce resistance and potentially make the treatment much better and give these patients a much better chance.”
It all has to do with a protein called SMYD3 that is highly expressed in small cell lung cancer and some other cancers. Healthy lung tissue has very little SMYD3, which led the researchers to think that getting rid of the protein might target cancerous cells while sparing healthy ones.
To test this hypothesis, the researchers created mouse models of human disease by grafting cancerous cells from two people with small cell lung cancer. One set of cells came from a patient who had not yet been treated, so the cells had no chance of developing resistance. The other came from a patient who had been treated with and became resistant to standard platinum-based therapy.
When the tumors in mice grew substantially enough, the researchers treated them with an inhibitor of SMYD3 and with cyclophosphamide. But inhibiting SMYD3 alone didn’t sufficiently slow down the growth of the tumors. Similarly, cyclophosphamide alone had weak results.