Scientists conducting a preclinical study at the Peter MacCallum Cancer Centre (the ‘Peter Mac’), in Melbourne, believe they’ve developed an experimental blood cancer therapy that may assist treatment of multiple myeloma in the future.
The research is published today in the journal Molecular Cell.
Multiple myeloma is a type of blood cancer that originates in plasma cells – immune cells in the bone marrow that normally produce protective antibodies.
These abnormal plasma cells multiply and spread rapidly through bone marrow, inhibiting the body’s capacity to make normal blood cells and productive antibodies, thus reducing an individual’s ability to fight infection.
“Multiple myeloma accounts for about 1% of all cancers in Australia,” says study senior author Professor Ricky Johnstone, Peter Mac’s executive director of cancer research. “While the survival rates have been increasing and there’s more therapies available now, it is still classified as an incurable disease. So that’s why we’re looking for new treatments for our patients.”
The disease usually occurs in people aged over 60 and it’s more common among men. The five-year survival rate for patients is just over 50%.
The Peter Mac researchers were exploring the effects of new drugs on myeloma-promoting enzymes.
“We came at it from a genetics perspective,” says Johnstone. “We were looking for genes that were important for the survival and proliferation of myeloma, and we identified two such genes that are very closely related. One’s called P300, and the other one is CBP.”
The exact role of P300 and CBP in cancer wasn’t completely understood, and until very recently no drugs had been developed to inhibit their activity.
“At the time [of our genetics research], a company called AbbVie pharmaceuticals in the USA had just made a small molecule that inhibited both of those enzymes,” says Johnstone. “So we contacted the company, and they gave us the compound. And then we did all of our studies with that compound and backed that up with genetic studies. So it really is a nice collaboration between academia and industry.”
Johnstone emphasises that the research is at preclinical stage, with work up until now limited to studies in mice and human cells in the laboratory.
Study lead author Dr Simon Hogg says the main discovery was that multiple myeloma is highly sensitive to this new therapy, “more so than many other cancers”.
“These drugs can quickly turn off key cancer-causing genes, called transcription factors, that directly control the growth of multiple myeloma,” Hogg says.
Transcription is a very important process in cancer, Hogg explains, because cancer cells need to maintain high levels of transcription to support fast growth.
This experimental therapy works by specifically turning off many important cancer-causing genes, lowering rates of transcription in the cancerous plasma cells and leading to their death. The researchers learned that the therapy is also effective against certain types of prostate cancer, which are also reliant on the P300 and CBP enzymes.
Johnstone says that his team also looked at how the therapy worked in combination with other drugs, and that they’d identified another drug that enhanced its efficacy.
“It’s exciting to see these positive results in the lab and get a glimpse of the impact this new experimental therapy might have for patients with multiple myeloma,” he says.
The next step is to move to clinical trials, but rapid progress is unlikely.
“We don’t want to over-promise anything here,” says Johnstone. “The preclinical work was encouraging, and we know that AbbVie are keen to progress and see whether they could conduct some clinical trials, hopefully with us here at the Peter Mac. We hope that this will eventually benefit our patients.”
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Ian Connellan is editor-in-chief of the Royal Institution of Australia.
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