Save Ted Kennedy from Deadly Brain Tumor (Glioma)!

The US Senator Ted Kennedy (76) was recently found to suffer from a deadly (malignant) brain tumor called glioma. The mean survival time of glioma patients is only 6 months. In other words
Ted might be able to see the outcome of November election where Barack Obama is expected to win the US presidential race against John McCain, if Ted is lucky. So far no effective (FDA-approved) therapeutics for glioma is available in the market. Thus, it is likely that MGH doctors in charge of Ted's glioma treatment would try a combination of radiotherapy and conventional chemotherapeutics such as cysplatin and 5-FU (so-called DNA poisons). The major cause of death of glioma or melanoma patients is not the growth of their tumors per se, but their metastasis/invasion to other sites within their body. Thus, it would be very difficult to save the life of glioma patients by DNA poisons or radiotherapy alone which kill the tumor cells, but cannot block their metastasis.

However, recently Seiji Kondo's and Rakesh Kumar's groups at MD Anderson Cancer Center in Houston jointly found that metastasis of glioma or short survival time of glioma patients depends on an oncogenic kinase (an enzyme) called PAK1. The higher this kinase activity, the shorter the survival time of glioma patients. In culture of glioma cells, inhibition of this kinase results mainly in the suppression of cell invasion (associated with metastasis). In other words, anti-PAK1 drugs would be potentially useful for the treatment of Ted's glioma. Our own group in Melbourne, Rakesh's group and a few others recently established that PAK1 is required for the growth of more than 70% of human (solid) cancers including breast and prostate cancers, pancreatic cancer and melanoma, MM (multiple myeloma) and NF (neurofibromatosis) tumors. Thus, we have developed or identified a series of anti-PAK1 drugs from synthetic chemicals or natural products.

These anti-PAK1 drugs block not only the growth of these PAK1-dependent cancer cells, but also their metastasis and angiogenesis (blood vessel formation around solid tumors), all of which require PAK1.

Among these natural anti-PAK1 products, an antibiotics called FK228 is the most potent (IC50 is around 5 pM), and our group and others confirmed that FK228 can suppress the growth of NF tumors, pancreatic, breast and prostate cancers in mice, and it is now in clinical trials (phase 2) for CTCL (cutaneous T-cell lymphoma). Among the natural anti-PAK1 products available in the market, two propolis (bee wax) extracts are so far the most effective in suppressing the growth of NF tumor, pancreatic, breast and colon cancers in mice. One is Bio 30, a CAPE-based water-miscible extract of NZ (New Zealand) propolis. CAPE is caffeic acid phenethyl ester, the major anti-cancer ingredient in propolis from Europe, Far East and Oceania, and NZ propolis has the highest CAPE content. The other is GPE, an ARC (artepillin C)-based green propolis extract from Brazil. Like CAPE, ARC also selectively blocks the oncogenic PAK1 signaling.

http://homepage2.nifty.com/daikon_tom/nfj/nfj_2007_06.htm

Thus, in principle, both Bio 30 and GPE would be among the alternative therapeutics for glioma, although nobody has ever tested their therapeutic efficacy on human glioma in vivo, in either mouse models or clinically. These propolis extracts not only block selectively the cancer cell division, metastasis and angiogenesis, but also boost the immune system which is badly damaged by radiotherapy or conventional chemotherapy. For these reasons, personally I would recommend Ted or any other glioma patients to try Bio 30 or GPE, if the combination of radiotherapy and conventional chemotherapy fails to improve their quality of life effectively.

Congratulations on the successful surgery of Ted's glioma at Duke!
http://edition.cnn.com/2008/POLITICS/06/02/kennedy.surgery/index.html


Signal Therapy of Glioma

More recently Qin Yu's group at Mount Sinai Medical School demonstrated that Merlin, a PAK1 inhibitor (NF2 gene product), can suppress the growth of glioma in mice. Thus, we have a great hope that propolis such as Bio 30 and GPE can be used for the therapy of glioma.

http://www.ncbi.nlm.nih.gov/pubmed/18632626?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Meanwhile we recently confirmed that Bio 30 indeed blocks the growth of human glioma cells in vitro (cell culture) very effectively as NF tumor cells, and we now began to test its therapeutic effect on fast-growing human glioma xenograft in mice.