Authors: Ming C. Liau, Christine L. Craig, Linda L. Baker.
The objective of this article is to rectify the inadequate cancer therapies focusing on the killing of cancer cells (CCs). Cancer is evolved due to wound unhealing because of the collapse of chemo-surveillance. Healing the unhealed wound should be the most appropriate strategy of cancer therapy. Wound healing requires the proliferation and the terminal differentiation of progenitor stem cells (PSCs). Chemo-surveillance is the nature’s creation of allosteric regulation to ensure perfection of wound healing. The collapse of chemo-surveillance caused by pathological assaults including carcinogens results in wound unhealing that forces PSCs to proliferate. The proliferation of PSCs is limited by contact inhibition. PSCs are then forced to evolve into cancer stem cells to escape contact inhibition. It takes a single hit to silence ten-eleven translocator-1 enzyme (TET-1) to convert PSCs to become cancer stem cells (CSCs), which is a task easily accomplished by PSCs equipped with abnormally active methylation enzymes (MEs). The proliferation of CSCs is still unable to heal the wound, because the problem is the collapse of chemo-surveillance unable to achieve terminal differentiation of PSCs, not the deficiency of PSCs. So, chromosomal abnormalities set in such as translocations to activate oncogenes or deletions to inactivate suppressor genes eventually forcing CSCs to become full blown cancer cells (CCs) with much faster replication capability than CSCs.
Since cancer is caused by wound unhealing. The process of wound healing is most appropriate to solve cancer. Induction of terminal differentiation of PSCs is a critical mechanism of wound healing, which is accomplished by the destabilization of abnormal MEs. MEs in cells expressing telomerase are abnormal, because MEs tend to associate with telomerase to turn these enzymes abnormal in favor of cell growth that is the most critical issue of cancer. The solution of abnormal MEs is very critical to the success of cancer therapy. When abnormal MEs is solved, replicating cells with abnormal MEs will be induced to undergo terminal differentiation. By completion of terminal differentiation, chromosomal abnormalities important for speeding up cell replication can also be put to rest. Oncogenes and suppressor genes are cell cycle regulatory genes, which have important roles to play when cells are in cell cycle replicating, but when cells exit cell cycle to undergo terminal differentiation they have no roles to play. CSCs are critically linked to wound unhealing. Destabilization of abnormal MEs is the only option to solve the issue of CSCs. It can also solve the issue of CCs by turning these cells into terminally differentiated cells unable to replicate, but it cannot make the tumor to go away. The tumor residue is harmless. If it is annoying, it can be safely removed by surgery.
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