Page 56 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰X機遇與未來大會手冊
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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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