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The goal and challenge toward living with cancer peacefully
Lu-Hai Wang 1,2
1 Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402
2 Chinese Medicine Research Center, China Medical University, Taichung 40402
Abstract
The major challenges of cancer treatment and subsequent management are recurrence, drug
resistance and metastasis due to post treatment residual cancer cells including cancer stem cells
(CSCs), which are thought to be involved in the development of the above phenomena. Even
the most advanced West medicine treatments inevitably would leave behind residual cancer
cells, which will recur soon or later. Accumulating evidence has indicated that integrated West
and East medicine treatment of cancer yields better outcome than either alone. This study aims
to develop Chinese herbal medicine-based adjuvant therapy to minimize cancer recurrence after
West medicine treatment. For this purpose, we have developed two remedies of botanical
extracts, one is to inhibit tumor growth and metastasis via immune modulation, and the other is
to inhibit neoangiogenesis and the growth of CSCs.
The first one is a compound herbal formulation, which we named HBK. HBK contains
polysaccharides including beta-glucans, flavonoids, ergosterol, polyphenolic compounds,
catechin and tannins, which are known to pertain immune modulatory and anti-oxidant effects.
The QC and consistency of HBK was monitored by HPLC and mass spectrometry. Using an
immune competent mouse lung cancer model, we found HBK was able to cause reprogramming
of the immune landscape in tumor microenvironment to enhance tumor-inhibiting and to reduce
tumor-promoting immune cells, namely to convert a “cold” to “hot” tumor. The sera from HBK
treated mice contain elevated levels of anti-tumor immune cytokines and anti-oxidant enzymes.
RNA seq analysis of the HBK treated tumors revealed alterations of immune modulatory
pathways including down regulation of several tumor-promoting molecules such as MYD88,
TRIF, NFkB, and p-NFkB. The HBK has been developed as a health food, tech transferred and
marketed. Furthermore, we have observed that HBK also has the anti-aging effect using mouse
cell line and Drosophila systems.
The second remedy is a single botanical extract named BEP1, which is able to preferentially
and potently inhibit the growth of cancer stem cells, as well as to inhibit tumor growth in an
immune competent mouse breast cancer model. BEP1 also reduced the CSC population in
BEP1 treated tumors and potently inhibited CSC-derived tumors. The inhibition of CSCs and
their protein biomarkers was likely via the beta-catenin and VEGFR pathways. Consistently,
BEP1 was shown to potently inhibit HUVEC angiogenesis in vitro. The IC50 for inhibiting the
growth of CSCs is much lower than that for inhibiting the growth of normal cells and cancer
cell population at large. This suggests that BEP1 in its very low dosage will be sufficient to
inhibit CSCs, giving the opportunity that it can be developed as a health food supplement
similar to HBK for long term adjuvant therapy of cancer patients.
In summary, combined treatment with HBK and BEP1 of the post treatment cancer patients
may be able to prolong and even prevent cancer recurrence.
Keywords: Cancer stem cells; HBK; Immune modulatory; Anti-oxidant; Immune landscape;
Anti-aging; Angiogenesis; Adjuvant therapy
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