Cell Dynamics in the Wound Healing Process in Tumor Environment After Treatments

Abstract

Although the failure of cancers treatments has been mostly linked with the existence of resistant cells or cancer stem cells, new findings show a significant correlation between circulating inflammatory biomarkers and treatment failures. Most cancer treatments cause necrotic cell deaths in the tumor microenvironment. Necrotic cells send signals to the immune cells to start the wound healing process in the tissue. Therefore, we assume after stopping treatments there is a wound that needs to be healed. The stochastic simulations of epithelial cell dynamics after a treatment, which only kills cells without changing the tumors inflammatory environment, show that higher fitness of cancer cells causes earlier relapses. Moreover, the tumor returns even if a single cancer cell with high fitness remains in the wounds boundary after such treatments. Although the involvement of cancer cells in the wound healing after treatments lead to the fast relapse, the cancer cells outside of the wound can also cause a slow recurrence of the tumor. Therefore, the absence of relapse after such treatments implies a slow-developing tumor that might not reach an observable size in the patients life time. Conversely, a large solid tumor in a young patient suggests the presence of high fitness cancer cells and therefore a high likelihood of relapse after conventional therapies. Additionally, the location of remaining cancer cells after treatments is a very important factor in the recurrence time. The fastest recurrence happens when a high fitness cancer cell is located in the middle of the wound. However, the longest time to recurrence corresponds to cancer cells located outside of the wounds boundary.