Pipeline – Aurora/FLT
About Aurora Kinases
Aurora kinases A and B are required for cells to both enter and proceed through mitosis, which is the process by which copies of the duplicated DNA chromosomes are segregated into two daughter cells. Moreover, Aurora kinases are over-expressed in a variety of cancers including pancreatic, ovarian, colon, breast, liver, lung, thyroid and bladder cancer. These cellular proteins therefore represent attractive targets for treating a wide range of cancers.
About FLT Kinases
The FLT kinases (FMS-like tyrosine kinases) have been demonstrated to be important in many stages of tumour development.
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Specifically:
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Flt3
Mutations to FLT3 have been observed in many acute myeloid leukemia (AML) patients resulting in either higher levels of the intracellular protein or higher activity versions of the enzyme. Mimicking such mutations to FLT3 in biological systems has been to confer growth factor independence in leukemic cell lines and give rise to an AML-like myeloproliferative syndrome.
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Flt4
Flt4, as well as being a driver in lymph angiogenesis, controls the mobilisation of cancer cells, a key process involved in metastasis, the main cause of death in cancer patients. A drug inhibiting Flt4 would be expected to prevent tumour spread.
A dual Aurora/FLT inhibitor
A single drug inhibiting the enzyme activity of Aurora and one of the FLT kinases would be expected to exert its therapeutic effect by blocking more than one cause of cancer progression, ideally providing a more effective cancer therapy.
Sareum have produced novel inhibitors which inhibit both Aurora and FLT4 activity. These compounds are currently being optimised in order to produce drugs which reduce or ablate solid tumours whilst also preventing the spread of secondary tumours.
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