Revolutionising Treatment for Multiple Myeloma

[box] Utsav Radia shines a light on research into the treatment of Multiple Myeloma [/box]

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Scientists at Imperial, led by Professor Guido Franzoso, have developed a new drug to be used in patients with multiple myeloma, a rare type of cancer affecting 4,800 new people every year in the UK.

Multiple myeloma results from the proliferation of cancerous antibody-secreting cells (called neoplastic plasma cells) in the bone marrow and other tissues. Physiologically, these plasma cells are responsible for synthesising protective immunoglobulins (a family of proteins that include antibodies) in response to a specific antigen (which is usually foreign). However, in a cancerous state, these plasma cells start to secrete lots of abnormal (and often immature) immunoglobulin molecules, known as paraproteins.

Patients with multiple myeloma usually present with bone pain or a pathological fracture. Others may even present with symptoms of blurred vision (that may result from hyperviscosity of the blood due to high levels of paraprotein), kidney damage, anaemia or even infection. Interestingly, in the early stages, multiple myeloma usually doesn’t cause any symptoms and is usually picked up after a routine blood or urine test, due to the presence of the abnormal immunoglobulins. The clinical and pathological features of multiple myeloma are mainly due to direct effects of the tumour (bone invasion or fractures), metabolic effects of the neoplastic cells (high plasma uric acid and calcium), the damaging effects of the paraprotein (such as peripheral neuropathy or renal failure) and impaired immunity as a result of reduced healthy immunoglobulins.

Currently, multiple myeloma is treated with two aims in mind: to help keep the myeloma under control and to help with symptom relief. Treatment combinations to control the myeloma usually consist of three classes of drugs: a chemotherapy drug (e.g. cyclophosphamide), a corticosteroid (e.g. prednisolone) and either thalidomide or velcade. Unfortunately, often patients tend to relapse in which case additional anti-myeloma treatments have to be given, which add to the plethora of side effects that patients experience.

Researchers at Imperial have reported laboratory findings that show the new drug, DTP3, kills myeloma cells in human cells and mice without causing any toxic side-effects. The drug uses a completely different mechanism of action compared to other cytotoxic drugs. DTP3 targets a biochemical step in a process called the NF-κB pathway, which is implicated in switching off the normal cellular mechanisms that naturally lead to cell death, hence prolonging (cancerous) cell survival.

Professor Franzoso, lead of the study, explained “we had known for many years that NF-κB is very important for cancer cells, but because it is needed by healthy cells, we did not know how to block it specifically…blocking the GADD45β/MKK7 segment of the NF-κB pathway with our DTP3…[that] selectively kills myeloma cells could offer a completely new approach to treating patients”.

Further work is now being done to commercialise DTP3 and other candidate drugs based on Professor Franzoso’s research to ensure the quickest and safest way to administer this treatment in patients with multiple myeloma. A trial of this drug, funded by the MRC, US National Institutes of Health and Cancer Research UK is due to take place in late 2015.

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