The Molecular and Cellular Strategies of Glioblastoma and Non-Small-Cell Lung Cancer Cells Conferring Radioresistance

Abstract

Ionizing radiation (IR) has been shown to play a crucial role in the treatment of glioblastoma (GBM; grade IV) and non-small-cell lung cancer (NSCLC). Nevertheless, recent studies have indicated that radiotherapy can offer only palliation owing to the radioresistance of GBM and NSCLC. Therefore, delineating the major radioresistance mechanisms may provide novel therapeutic approaches to sensitize these diseases to IR and improve patient outcomes. This review provides insights into the molecular and cellular mechanisms underlying GBM and NSCLC radioresistance, where it sheds light on the role played by cancer stem cells (CSCs), as well as discusses comprehensively how the cellular dormancy/non-proliferating state and polyploidy impact on their survival and relapse post-IR exposure.

Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments

“…The contribution of hypoxia-driven mechanisms to GSC-mediated radioresistance, as discussed by Alhaddad et al [ 40 ] resonates with the findings of Hsieh et al [ 45 ] NADPH oxidase subunit 4, identified as a mediator of cycling hypoxia-promoted radiation resistance in glioblastoma multiforme, underscores the intricate relationship between the tumor microenvironment and resistance mechanisms. The role of hypoxia in shaping the GSC phenotype adds a layer of complexity to the design of targeted therapies, necessitating strategies that account for the dynamic nature of the tumor microenvironment[ 2 , 6 , 46 ].…”

“…Additionally, Yi et al [ 30 ] targeted CK1α to reduce resistance to TMZ and radiotherapy, emphasizing the intricate network of pathways involved in GSC-mediated resistance. The study by Alhaddad et al [ 40 ] delves into the role of autophagy induction in promoting M2-like macrophage polarization, thereby contributing to radioresistance[ 41 ]. This contrasts with Li et al [ 42 ] where PI3Kγ inhibition suppresses microglia/TAM accumulation in the glioma microenvironment by inhibiting autophagy, ultimately promoting an exceptional response to TMZ[ 2 ].…”

“…The study by Huang et al [ 37 ] further emphasized the role of CK2α/PRMT6/RCC1 pathway, which was targeted using EPZ020411, resulting in a reduction in radioresistance. The study by Alhaddad et al [ 40 ] provides insights into GSC-mediated reprogramming of the tumor microenvironment, specifically in the context of macrophages and microglia. The creation of GSC niches at the tumor border, as reported by Hide et al [ 47 ] emphasizes the dynamic interplay between oligodendrocyte progenitor cells, macrophages/microglia, and the GSC microenvironment.…”

“…The intercellular crosstalk between GSCs and immune components suggests a complex landscape that contributes to therapy resistance. The study by Alhaddad et al [ 40 ] emphasizes the broader influence of GSCs on the tumor microenvironment and therapy response. The creation of GSC niches at the tumor border, as demonstrated by Hide et al [ 47 ] signifies the role of GSCs in orchestrating the cellular composition of the microenvironment.…”

PI3K/mTOR inhibitors promote G6PD autophagic degradation and exacerbate oxidative stress damage to radiosensitize small cell lung cancer

“…SCLC is highly sensitive to radiotherapy in the early stages of treatment, but radioresistance inevitably develops in a significant proportion of patients [ 32 , 33 ]. Cancer radioresistance is an intricate phenomenon that has attracted a lot of attention, and there are two main hypotheses to explain it [ 34 , 35 ]. First, tumor cells with both high and low sensitivity to radiation exist in tumors.…”