Factors and molecular mechanisms of radiation resistance in cancer cells

PURPOSE: The aim of this work is to review the published studies on radiation resistance mechanisms and molecular markers involved in different tumors. The revision has been focused in the last 5 years (2016-2021). CONCLUSIONS: Radioresistance is a cause of concern as it causes failure of radiation therapy and subsequent tumor relapse. Combination chemotherapy and radiation therapy are clinically successful in treating many types of tumors. Despite continued improvements in cancer treatment, locoregional recurrence or metastatic spread continues to occur in a high proportion of patients after being treated with radiation therapy or combination treatments. There is strong evidence that cancer stem cells contribute to radiation resistance, contributing to treatment failure. The mechanisms of radiation resistance in different tumors are not fully understood. A better understanding of cancer stem cells and the associated signaling pathways that regulate radiation resistance will open up new strategies for treating cancer by radiation therapy. Radiation can damage malignant cells mainly by the induction of DNA double-strand breaks. However, in some tumors appear resistant cells that repopulate the tumor following therapy leading over time to the failure of the treatment. Native mechanisms and induced pathways are the cause of radiation resistance. It has been described that numerous molecular markers acting through numerous mechanisms of action involved in radiation resistance, such as apoptosis resistance, alterations of cell growth, proliferation and DNA repair, hypoxia, increase in invasiveness and migration capacity, cell cycle alterations, and expression of heat shock proteins, among others. Therefore, resistance to radiation is a multifactorial phenomenon that, in different cell types, occurs through different regulatory mechanisms in which different molecules intervene. Resistance can be acquired by altering different regulatory pathways in different tumors. The knowledge of radiation resistance markers could help in the classification and treatment of patients with more aggressive tumors.