Anagrelide: Treatment for Cancer

This project relates to the use of a radically new, first-in-class approach to the treatment of cancer, potentially applicable across a wide range of solid tumours. Currently, newer cancer treatments involve immunotherapy which stimulate the patients’ own immune system. Anagrelide could be complementary to such treatments rendering circulating cancer cells more susceptible to attack by the body’s own “killer” T cells and could thus offer a valuable new adjunctive therapy.

Anagrelide is currently used to reduce elevated platelets and lower the thrombotic risk in myeloproliferative diseases associated with high platelet counts. It is now recognised that platelets also play a key role in the growth and metastatic spread of tumours. At the last annual meeting of the American Society of Haematology, perhaps one of the most widely attended events in this field, several key opinion leaders presented data on the underlying mechanisms by which the platelet-tumour interaction is mediated and how the reduction of platelets could potentially help minimise tumour growth and metastasis.

Anagrelide has the potential to be developed as an effective anti-cancer agent but is presently limited by the cardiovascular side effects seen after administration of the current capsule formulation. This gives rise to an initial first pass effect in the liver generating a cardio-stimulatory metabolite upwards of 40 times more potent than the drug itself. An oro-mucosal spray formulation of anagrelide could reduce these side-effects by avoiding first-pass generation of this highly potent cardio-excitatory metabolite.

The role of platelets in cancer

There is compelling experimental and clinical evidence confirming the crucial role played by platelets in cancer progression. Platelets accomplish this in a number of ways:

  • Immune system suppression
  • Tumour growth and metastases

As can be expected this results in more of the above resulting in faster growing tumours that are protected from the immune system that continue to generate more platelets.

Potential role of anagrelide in cancer treatment

Anagrelide by itself will not cure cancer. Anagrelide will slow the production of the platelets reducing the impact of these protectors of, and promoters of, tumour growth. Anagrelide is therefore proposed as an adjuvant or neo-adjuvant therapy (modifier/promotor of the effect of another drug). By reducing the production of platelets, anagrelide will stop or reduce the feedback loop discussed above and will further expose the cancer cells to the immune system. This means that by potentially slowing the growth of the tumours the existing cancer drugs have a greater chance of reducing the tumour burden. It also has the potential to improve the performance of some the most exciting new immunotherapies that are currently making their way onto the market.

The potential of reducing the platelet count in patients with solid tumours includes: greater progression free survival; reduced tumour burden; and even potentially greater cure rates. 

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