Effect of inosine on recurrence of tumor after radiation therapy: A mathematical investigation

Abstract

Tumor invasion that marks the transition from localized growth to aggressive spread is critical in cancer biology. It involves the breakdown of surrounding tissues through matrix degradation enzymes, such as urokinase plasminogen activator and matrix metalloproteinases, to promote cancer cells migration. Understanding invasion pathways is crucial for developing effective therapies and improving patient outcomes. There is a significant progress in cancer treatments; however, the treatments such as radiotherapy and chemotherapy are ineffective many times in the sense that some cancer cells survive, leading to tumor recurrence. It has been observed that dead cells play a key role in cancer recurrence. The dead cells, particularly due to treatments like radiation or chemotherapy, release signals and cellular components, including nucleotides like inosine, cytokines, and growth factors. These factors influence the tumor microenvironment and promote the survival and proliferation of nearby cancer cells. In this article, a novel mathematical model is proposed to investigate the effects of inosine on tumor recurrence and invasion. The simulated results are in very good agreement with the experimental and numerical results of the literature. The model simulated the inosine generation after some time of radiotherapy treatment withdrawal, and it achieves a log-normal profile. In line of experimental observations, it is obtained that the cancer cells proliferate with usual proliferation but once inosine gets generated from the dead cells, the proliferation intensity of cancer cells is enhanced significantly.