Improving radiotherapy in cancer treatment: Promises and challenges

Abstract

Effective radiotherapy for cancer has relied on the promise of maximally eradicating tumor cells while minimally killing normal cells. Technological advancement has provided state-of-the-art instrumentation that enables delivery of radiotherapy with great precision to tumor lesions with substantial reduced injury to normal tissues. Moreover, better understanding of radiobiology, particularly the mechanisms of radiation sensitivity and resistance in tumor lesions and toxicity in normal tissues, has improved the treatment efficacy of radiotherapy. Previous mechanism-based studies have identified many cellular targets that can affect radiation sensitivity, notably reactive oxygen species, DNA-damaging response signals, and tumor microenvironments. Several radiation sensitizers and protectors have been developed and clinically evaluated; however, many of these results are inconclusive, indicating that improvement remains needed. In this era of personalized medicine in which patients’ genetic variations, transcriptome and proteomics, tumor metabolism and microenvironment, and tumor immunity are available. These new developments have provided opportunity for new target discovery. Several radiotherapy sensitivity-associated “gene signatures” have been reported although clinical validations are needed. Recently, several immune modifiers have been shown to associate with improved radiotherapy in preclinical models and in early clinical trials. Combination of radiotherapy and immunocheckpoint blockade has shown promising results especially in targeting metastatic tumors through abscopal response. In this article, we succinctly review recent advancements in the areas of mechanism-driven targets and exploitation of new targets from current radio-oncogenomic and radiation-immunotherapeutic approaches that bear clinical implications for improving the treatment efficacy of radiotherapy.

mTOR-Mediated Antioxidant Activation in Solid Tumor Radioresistance

“…Ionizing radiation mainly causes apoptosis in tumor cells [143]. Various types of cell death including necrosis, apoptosis, pyroptosis, ferroptosis, and autophagy could be induced depending on the properties of adjuvants [144][145][146][147]. e inhibition of mTOR signaling induces autophagy [148].…”

Rectification of radiotherapy-induced cognitive impairments in aged mice by reconstituted Sca-1+ stem cells from young donors

“…Despite its many uses, the use of radiation therapy has several drawbacks [54][55][56]. In this study, we carried out whole-body irradiation at 10 Gy to induce both cognitive impairments and depletion of BM HSCs [57,58].…”

Synergetic role of senna and fennel extracts as antioxidant, anti-inflammatory and anti-mutagenic agents in irradiated human blood lymphocyte cultures

“…ROS, especially hydroxyl radicals (OH . ), play an important role in DNA damages and other radiation-induced injuries (Chen & Kuo, 2017).…”