New drug combination offers new hope to patients

blog-Rick-Pearson

The Leukaemia Foundation is proud to have funded four researchers at the Peter MacCallum Cancer Centre working on the development of a new drug, CX-5461, currently being evaluated in a clinical trial for patients with advanced blood cancers.

Results from the trial have been promising to date, however the research team has found that CX-5461 could be even more effective when used in combination with another commonly used cancer drug.

The new combination drug therapy has shown to double survival times in pre-clinical laboratory models.

The study, published overnight in the Cancer Discovery journal, builds on a world-first clinical trial underway at Peter Mac which uses the drug CX-5461 to treat patients with incurable blood cancers such as myelomalymphoma and leukaemia.

The trial has shown promising results to date, however the research team has found that CX-5461 could be even more effective when used in combination with another drug, Everolimus, which is already used to treat other cancers.

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

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

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

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

“As a result of this research breakthrough, fifteen patients are currently involved in a phase 1 clinical trial of CX-5461 – a compound that our 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.

“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 that this approach may be generally applicable for a range of cancer types.”

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 this new research provides further confidence that researchers are 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. To date 15 patients have been treated on the first-in-human clinical study with a number of patients experiencing prolonged benefit.

“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.”

More than 12,000 Australians are diagnosed with blood cancer annually (approximately 10% of all cancers) and around 4,000 Australians lose their lives to the disease each year.

* This research is supported by the National Health and Medical Research Council; Cancer Council Victoria; the Leukemia Foundation; Prostate Cancer Foundation of Australia; Cancer Australia; Victorian Cancer Agency, Australian Cancer Research Foundation and Peter MacCallum Cancer Foundation. Collaborators include the John Curtain School of Medical Research at the Australian National University and Monash University.

 

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