Our research at The University of Glasgow is searching for cures for people with CML, and we are finding new ways to target CLL. Our TAP centre is based in Glasgow, and we have trials that are looking at new treatments for people who are in the advanced stages of MPN or CML.
With the advent of targeted tyrosine kinase inhibitors (TKIs) for CML, most people living with this blood cancer can now take a single pill and control their disease. But they are not completely cured, and some people are unable to tolerate the side effects of their treatment, or become resistant to it, or find that their CML has come back.
Over the last few years, Professor Holyoake along with Dr David Vetrie have been focusing on leukaemia stem cells that maintain the leukaemia in the bone marrow. Although these slow growing cells make up only a tiny proportion of the total population of cancer cells, they can produce a steady stream of new CML cells. And because they are less active than the other cancer cells, they are harder to target with current drugs, and that is why the disease is difficult to eradicate completely.
Researchers have now identified three key cellular networks that are crucial in controlling survival of CML stem cells. Now the team want to see how these networks interact with each other, and how they may be targeted with new drugs to improve the outcome for people with CML.
We are also supporting research that is hoping to find new treatments and combinations of drugs for chronic lymphocytic leukaemia (CLL). Although the majority of people initially respond to conventional chemotherapy, many will relapse due to the re-emergence of CLL cells that evaded initial treatment. In these cases, people with CLL can quickly run out of options.
It is now appreciated that the CLL cells interact with several types of other surrounding cells within the lymph nodes and bone marrow. These healthy cells are manipulated by the CLL cells so they offer protection from currently-used treatments, such as chemotherapy.
Dr Alison Michie and her team are focussing on a protein called mTor, which plays a central role in regulating key proteins responsible for CLL cell protection, survival and disease progression. By understanding the role mTOR plays in CLL, researchers hope to find new drug targets that could stop or reverse the disease.
We are supporting two Trials Acceleration Programme (TAP) studies which are based at The Beatson West of Scotland Cancer Centre in Glasgow.
Myeloproliferative Neoplasms (MPNs) are rare blood cancers that in some cases may transform to an acute leukaemia which is very difficult to treat. When MPN progresses to the advanced ‘blast phase’, treatment options are very limited. And while progress continues to be made in managing early phase MPN, research into the advanced stage of the disease has been relatively neglected so far.
Dr Mark Drummond is running the PHAZAR trial, which wants to see if combining a biological therapy called ruxolitinib with azacitidine, a chemotherapy, could offer a new approach to treat people with advanced MPN. On their own, ruxolitinib has been shown to be effective at controlling MPN symptoms, and azacitidine has improved survival in people with a type of MPN called myelodysplastic syndrome (MDS), and AML. The aim of the trial is to find a safe dose of azactidine and ruxolitinib when combined, see how well treatment works, and to find out more about the side effects in people with advanced MPN.
Professor Mhairi Copland is leading another TAP trial called MATCHPOINT, which is looking at treatment options for people who are in an advanced blast phase of their CML.
Although TKIs work for many people with CML, this improvement remains limited to people who receive TKI treatment whilst in the chronic phase of their disease. Unfortunately, the majority of people whose disease has progressed to blast phase have already received all the available drugs in succession during the chronic phase, so there is no TKI available when they progress. If this happens, people are usually given intensive treatment comprising high dose of chemotherapy alongside a TKI, and then a stem cell transplant.
MATCHPOINT is looking at a conventional chemotherapy regimen called FLAG-IDA alongside a new TKI drug called ponatinib for people who are in the blast phase of their CML and who have had a stem cell transplant. Ponatinib works in a similar way to imatinib and nilotinib, in that it specifically targets BCR-ABL that is only found in CML cells. However, ponatinib was also designed to target mutated forms of the BCR-ABL that arise in people who become resistant to their TKI treatment, as well as other kinases implicated in blood cancer and solid tumours.
If found to be safe, researchers hope that this combination of drugs can be used in future trials to see whether we can improve the outlook for people with CML who are in blast phase.