Wound Unhealing as a Grave Issue of Cancer

Wound healing requires the proliferation and the terminal differentiation of PSCs, the most primitive stem cells expressing abnormal differentiation enzymes (MEs). Wound if not healed properly, PSCs may be forced to evolve into cancer stem cells (CSCs), and then to progress to faster growing cancer cells (CCs). Our carcinogenesis studies revealed that the numerous tiny preneoplastic hyperplastic nodules appeared in response to carcinogen challenge were the attempt of the liver to repair the damages created by carcinogen. These nodules represented the proliferation of PSCs displaying abnormal MEs. Most of these nodules disappeared when the damages were repaired. Only a few nodules which were not successful repaired, later developed to become large carcinomas. The employment of phenylacetylglutamine, which was an effective anti-cachexia chemical to protect the functionality of chemo-surveillance, could prevent carcinogenesis induced by potent carcinogens. These studies clearly demonstrated that carcinomas developed if wounds were not efficiently healed.

Perpetual proliferation of CCs was the most outstanding feature of cancer. Stop proliferation of CCs naturally became the top choice of cancer therapy. There were two options to stop proliferation of CCs: one by killing of CCs and the other by induction of terminal differentiation of CCs. Cancer was also made up by CSCs as a minor component. The option by killing of CCs was the choice of cancer establishments, which displayed the feature as anti-wound healing, clearly a wrong choice because cancer was caused by wound unhealing. The option by the induction of terminal differentiation was the choice of the nature which created chemo-surveillance to ensure perfection of wound healing to avoid cancer. This option displayed the feature as pro-wound healing, clearly the right indication of cancer therapy. CSCs play a major role on the fatal effects of cancer. The effectiveness of cancer therapy depends heavily on the ability to eradicate CSCs. Therapies based on killing of CCs were ineffective against CSCs because these cells were protected by drug resistance and anti-apoptosis mechanisms, whereas the induction of terminal differentiation was a critical mechanism of wound healing very effective to eradicate CSCs. Thus, the option by the induction of terminal differentiation was the right choice for cancer therapy.