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New drug combination turbo charges attack against cancer

Peter McCallum

Survival times have been doubled in early testing of a powerful new drug combination for patients with advanced blood cancers.

With funding support from the Leukaemia Foundation, researchers at the Peter MacCallum Cancer Centre in Melbourne have been working on the development of a new drug, CX-5461, currently being evaluated in a world-first clinical trial for patients with advanced blood cancers.

Results from the trial have been promising, however the research team has found CX-5461 could be even more effective when used in combination with another drug, everolimus, which is already used to treat other cancers.

The new combination of drugs has been shown to double survival times in pre-clinical laboratory models, effectively turbo charging the attack against cancer.

According to Professor Rick Pearson, Head of Peter Mac’s Cancer Signalling Laboratory, the research findings significantly enhance our understanding of how to kill off cancer cells before they have the chance to become resistant to treatment.

Targeting what cancer cells need to survive

“CX-5461 targets a particular process required for cancer cell survival. Our experiments show adding everolimus synergistically strengthens this attack, more rapidly and more effectively eradicating the killer disease,” Professor Pearson explained.

“We know all cells rely on ribosomes, which act like a factory producing the proteins essential for their growth and survival.

“Peter Mac researchers have previously shown certain blood cancers are far more reliant on these proteins than normal cells, and eliminating the protein production capability of ribosomes leads to the rapid death of cancer cells, while normal cells stay viable.”

As a result of the breakthrough, 15 patients are currently involved in a phase one clinical trial of CX-5461 – a compound the research team is developing with pharmaceutical company Senhwa.

“This novel therapy works to inhibit the ribosomes’ protein production capability, effectively starving the cancer cells of a key ingredient they need to survive and proliferate,” Professor Pearson added.

“By adding everolimus to this treatment, we have shown the potential for even more powerful results. A further study in collaboration with scientists at Monash University shows striking effects in the targeting of late-stage prostate cancer through a similar strategy indicating this approach may be generally applicable for a range of cancer types.”

More than 12,000 Australians are diagnosed with a blood cancer each year – accounting for approximately 10% of all cancers – and around 4,000 Australians lose their lives to these cancers each year.

A Leukaemia Foundation spokesperson says the results were promising for people with advanced blood cancers who often had a poor prognosis.

“This is a critical area of research and I thank each and every one of our generous donors who help to make vital research projects like this possible,” they said.

On the cusp of new treatment options for patients

Associate Professor Simon Harrison, Consultant Haematologist at Peter Mac and Principal Investigator on the CX-5461 first-in-human trial, says the new research provided further confidence researchers were on the right track.

“The prevalence and poor prognosis for people with advanced blood cancers demands the ongoing and intricate study of abnormal cell behaviour, which has been an indicator of cancer for over 100 years.

“With this new knowledge we can now work closely with pharmaceutical companies to potentially fast track the testing of this combination approach for the benefit of patients.”

The study was published in the Cancer Discovery journal.