MELBOURNE researchers have doubled survival times for advanced blood cancer in pre-clinical models through a combination of medications that shut down the “construction workers” of the cells.
By giving a commonly used cancer drug with a new type of medication — still undergoing a first in-humans clinical trial — Peter MacCallum Cancer Centre researchers have starved cancer cells of the key ingredients they need to survive and spread, while sparing healthy cells.
Three years ago, Peter Mac researchers showed that a new drug called CX-5461 could stymie the ability of ribosomes, which produce proteins vital for a cell’s growth and survival, leading to the rapid death of cancer cells. This class of drug is being tested in 15 patients, with a number of them experiencing “prolonged benefit”, said principal investigator Associate Professor Simon Harrison.
At the same time, head of Peter Mac’s Cancer Signalling Laboratory, Professor Rick Pearson, has been working on ways to shut down this pathway at different points with different drugs. Using the drug Everolimus, usually taken by patients with advanced kidney and pancreatic cancers, his team found that combining it with CX-5461 was even more effective at shutting down ribosomes.
“We hypothesised if we could hit the process harder by using other inhibitors that target the process at different points, we could actually have a better effect than just CX-5461. And we got a better effect than we hoped for,” Prof Pearson said. “By inhibiting that pathway, we actually get up-regulation of a protein which specifically kills cells. That’s part of the reason why we’re seeing these results with the combination therapy.”
In previous studies, mice that received CX-5461 lived for 35 days instead of 10 days. When combining CX-5461 with Everolimus, their survival was increased to 70 days. The results were published overnight in the journal, Cancer Discovery.
With 12,000 Australians diagnosed with blood cancers, including leukaemia and lymphomas, each year, Prof Pearson said the findings should give patients hope researchers were making “steps in the right direction” to find better ways of prolonging lives. “A lot of people are still dying, with 4000 Australians still losing their lives to blood cancers each year,” he said.
Prof Pearson said the next step was to get pharmaceutical companies on board for a clinical trial in human patients using both drugs.
Story source: Herald Sun