I have written previously on the difference between brute-force cancer therapies and highly focused new- generation ones in the pipeline. See the post From four-pound hammer to smart molecules – on cancer treatments. Radiation therapy and most forms of chemotherapy kill normal cells along with cancer cells – like the four-pound hammer approach to swatting flies. Suppose there were 1. a protein that would selectively kill cancer cells but be harmless to normal cells, and 2. safe and easy ways existed for triggering the action of that protein in cancer cells. The comment made yesterday by Res in response to my post Trojan-horse stem cells might offer an important new cancer therapy set me on the trail of TRAIL which appears to be just such a protein. TRAIL stand for tumor necrosis factor–related apoptosis-inducing ligand. TRAIL is also called APO-2L and consists of 281 amino acids. As pointed out earlier, “TRAIL induces apoptosis via death receptors (DR4 and DR5) in a wide variety of tumor cells but not in normal cells(ref).” “ — TRAIL delivery in anticancer experiments does not result in any deleterious effect on normal cells. Therefore, many oncologists predict that TRAIL has the potential to be developed as an anticancer drug that selectively restricts primary as well as metastatic tumours(ref)”
TRAIL appears to be the mechanism of anti-cancer action of the potential stem cell therapy mentioned in the previous post, where mesenchymal stem cells are loaded with TRAIL warheads and act as missiles that home in on cancer cells. Certain of the supplements in the Susceptibility to Cancer Firewall, particularly curcumin(ref), resveratrol(ref) and green tea, owe at least some of their anti-cancer effects to the operation of TRAIL. In the case of prostate and other cancers, curcumin inhibits the activation of NF-kappaB which makes them more sensitive to apoptosis by TRAIL(ref,ref,ref). Resveratrol appears to have the same effect in certain tumors(ref)(ref). The same appears to be true for EGCG, the major active constituent of green tea(ref). I speculate that other plant-derived polyphenols in the anti-cancer firewall might have similar effects, enhancing TRAIL-mediated death receptor activation in cancer cells. Possibly, most of the 39 inhibitors of NF-kappaB in the firewall might work to empower TRAIL and fight cancers in the same way.
It appears that combating cancers via TRAIL is now a major approach under research investigation. However, some cancer cells offer resistance to TRAIL-induced death receptor apoptosis. Using TRAIL with another anti-cancer therapy might be helpful in such cases. Velcade, a proteasome inhibitor, sensitizes cancer cells to TRAIL. It has been suggested that TRAIL might be combined with the anti-cancer drug Velcade to achieve a synergistic effect(ref).
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