Difference in Acquired Radioresistance Induction Between Repeated Photon and Particle Irradiation

Abstract

In recent years, advanced radiation therapy techniques, including stereotactic body radiotherapy and carbon–ion radiotherapy, have progressed to such an extent that certain types of cancer can be treated with radiotherapy alone. The therapeutic outcomes are particularly promising for early stage lung cancer, with results matching those of surgical resection. Nevertheless, patients may still experience local tumor recurrence, which might be exacerbated by the acquisition of radioresistance after primary radiotherapy. Notwithstanding the risk of tumors acquiring radioresistance, secondary radiotherapy is increasingly used to treat recurrent tumors. In this context, it appears essential to comprehend the radiobiological effects of repeated photon and particle irradiation and their underlying cellular and molecular mechanisms in order to achieve the most favorable therapeutic outcome. However, to date, the mechanisms of acquisition of radioresistance in cancer cells have mainly been studied after repeated in vitro X-ray irradiation. By contrast, other critical aspects of radioresistance remain mostly unexplored, including the response to carbon-ion irradiation of X-ray radioresistant cancer cells, the mechanisms of acquisition of carbon-ion resistance, and the consequences of repeated in vivo X-ray or carbon-ion irradiation. In this review, we discuss the underlying mechanisms of acquisition of X-ray and carbon-ion resistance in cancer cells, as well as the phenotypic differences between X-ray and carbon-ion-resistant cancer cells, the biological implications of repeated in vivo X-ray or carbon-ion irradiation, and the main open questions in the field.

The p53–53BP1-Related Survival of A549 and H1299 Human Lung Cancer Cells after Multifractionated Radiotherapy Demonstrated Different Response to Additional Acute X-ray Exposure

“…Several different irradiation (IR) schedules with or without chemotherapy are presently explored in the clinical practice of NSCLC therapy. In many cases of tumor recurrence after primary radiotherapy, patients can rarely be treated again with the same radiation regimen because the tumor might acquire radioresistance [28]. The proposed processes contributing to enhanced cellular tolerance to MFR included cell cycle checkpoint responses and activation of pro-survival signaling pathways.…”

CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer

“…Therefore, repopulation of tumors and regeneration of normal tissue are critical in the success of fractionated RT. The relationship between the 4Rs of RT and radioresistance acquisition has been summarized recently by Sato et al [ 174 ].…”

“…Some authors have suggested that the accumulation of DNA damage by repeated X-ray irradiation favors both EMT and CSCs enrichment, which increase oncogenic activity. Secondary induction of a CSC subpopulation by EMT also contributes to the induction of radioresistance [ 174 ]. The differences between photon and particle irradiation concerning the effects of repeated in vivo irradiation remain largely unknown.…”

Recent Progress of Potentiating Immune Checkpoint Blockade with External Stimuli—an Industry Perspective

“…Although antitumor immunity is induced by radiotherapy, the effect may be limited due to the presence of radioresistant suppressor cell types in the tumor microenvironment. [ 62 ] In addition, tumor irradiation induces the expression of immune checkpoint molecules, such as PD‐L1, and upregulates TGF‐β signaling, which triggers a wound healing response. This process may facilitate tumor recurrence.…”