Repurposed Dipyridamole as a cancer treatment

Repurposed Dipyridamole as a cancer treatment

Dipyridamole or DIP, has been found in numerous studies to reduce cancer tumour size, reduce metastasis, progression and inflammation whilst improving immune response and certain chemotherapy treatments; there is research with melanoma, breast cancer including TNBC, bone mets and colorectal cancer.

Dipyridamole is a safe and widely prescribed drug used in Ischemic disorders where the blood supply is limited to tissues - it inhibits thrombus formation by short-term vasodilation, Like aspirin, it is an anti-platelets drug, it limits platelet adhesion, and it has been used for many years with few, if any, side-effects.

Dipyridamole and cancer

Dipyridamole is also known to increase the concentration of the anticancer drugs 5-fluorouracil (5-FU), methotrexate, piperidine and vincristine in cancer cells and so increases the effectiveness of the treatment.

How it does this, is rather unclear. In 2016, Chinese researchers from the University of Changchun attempted to find out(1) and discovered two proteins were targets; one was a human checkpoint inhibitor, a target for some of the latest immunotherapy drugs.

Dipyridamole, platelets and increased melanoma survival

This was nothing new. In 1985, Doctors at St Helier and Kingston Hospitals treated stage III and Stage IV melanoma patients with 300 mg of Dipyridamole. Instead of 32% of the Stage IV patients surviving 5 years, their data showed 74% survived, with 100% of the Stage III patients surviving 5 years. (The results were reported in The Lancet, March 23rd 1985). Their research noted that they believed Dipyridamole stopped the cells from the primary tumour moving into and around the blood stream, thus reducing metastasis and death rates.

Which takes us back to platelets. Platelets help your blood clot when you cut yourself. But platelets also help cancer spread.

Cancer cells

   * Use platelets to enter the blood stream

   * Recruit platelets to help them hide from the immune system,

   * Use Platelet Derived Growth Factor to form new blood supplies,

   * And platelets help them move through the blood stream to distant tissues.

Without platelets they can’t do any of these things.

Platelets (and fibrinogen) also block the action of Natural Killer Cells(5). Blocking the action of platelets thus helps improve immune response. Platelets are thus involved in immune response and it is also known that they are involved in inflammatory response.

Many drugs are being developed to tackle these problems. But why invent new drugs when Dipyridamole can already solve these problems, and without real side-effects? In fact, there is a significant peer-approved 2017 review on the need to tackle platelets in the treatment of cancer(6).

Dipyrimadole and colorectal cancer drugs

As long ago as 1991, Sakaguchi and a team from Kyushu University Medical School in Fukuoka showed that Dipyridamole could enhance the effectiveness of both Adriamycin and 5-FU in colorectal cancer following surgery(3).

Dipyrimadole and breast cancer

In 2013 researchers from the University of Naples and the National Cancer Institute in the USA showed that Dipyridamole or DIP was effective against breast cancer and particularly Triple Negative Breast Cancer TNBC(2). In animal experiments DIP was shown to significantly reduce primary tumour growth, metastasis and breast cancer progression after intra-peritoneal use. Dr Daniella Spano concluded that while low dose DIP significantly reduced primary tumour growth and metastasis, high dose resulted in an almost total reduction in primary tumours.

A further study by Wang(4) showed dipyridamole could block primary tumours and reduce bone metastasis in breast cancer.

Dipyridamole dose for cancer

Dipyridamole is on the Repurposing Drugs in Oncology Database. It is also called Persantine. Research is turning an anti-platelets drug, into an anti-cancer drug. A dose of 300 mg per day is used to block heart attacks. There is little specific information on the doseto treat cancer.

Repurposed drug combinations – Dipyridamole and cimetidine

Many reviews of repurposed drugs make the point that combinations of drugs are important in treating cancer. In several studies, the simultaneous use of anti-histamines such as Tagamet (cimetidine) alongside Dipyridamole was shown to be important. There are numerous studies on histamines in the fight against cancer (7, 8).

The body's endogenous histamines help platelets stick to each other, primed for cancer's use and histamines stimulate cancer cell growth by activating an H2 receptor on the cancer cell membrane. There is research on Cimetidine, and Loratadine on this CANCERactive Website,

Go to: Can histamines like Cimetidine and Loratadine help fight cancer

* * * * * * * *

References

  1. Am J Transl Res. 2016; 8(12): 5187–5198.
  2. https://link.springer.com/article/10.1007%2Fs10585-012-9506-0
  3. https://www.ncbi.nlm.nih.gov/m/pubmed/1958858/?i=1&from=Sakaguchi%20Y[Author]
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829204/
  5. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killercell-mediated elimination of tumor cells.
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532630/
  7. https://www.ncbi.nlm.nih.gov/pubmed/7741034
  8. https://www.ncbi.nlm.nih.gov/pubmed/7605350
2019 Research
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