Radioresistance of Non-Small Cell Lung Cancers and Therapeutic Perspectives

Césaire, Mathieu; Montanari, Juliette; Curcio, H.; Lerouge, D.; Gervais, Radj; Demontrond, Pierre; Balosso, Jacques; Chevalier, François

doi:10.3390/cancers14122829

Cited by 29 publications

(17 citation statements)

References 105 publications

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“…NSCLC is known as a radioresistant cancer due to the presence of cancer stem cells, an epithelial-mesenchymal transition, and its high proportion of hypoxic cell populations [ 6 , 170 ]. RE has already been shown to act as a radiosensitizer in several cancer types ( Table 2 ) and this led to several clinical trials ( Table 3 and Supplementary Table S1 ).…”

Section: Discussion and Concluding Remarksmentioning

confidence: 99%

Recombinant Endostatin as a Potential Radiosensitizer in the Treatment of Non-Small Cell Lung Cancer

et al. 2023

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Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer, which is the leading cause of cancer-related deaths worldwide. Over the past decades, tumour angiogenesis has been intensely studied in the treatment of NSCLC due to its fundamental role in cancer progression. Several anti-angiogenic drugs, such as recombinant endostatin (RE), have been evaluated in several preclinical and clinical trials, with mixed and often disappointing results. However, there is currently an emerging interest in RE due to its ability to create a vascular normalization window, which could further improve treatment efficacy of the standard NSCLC treatment. This review provides an overview of preclinical and clinical studies that combined RE and radiotherapy for NSCLC treatment. Furthermore, it highlights the ongoing challenges that have to be overcome in order to maximize the benefit; as well as the potential advantage of combinations with particle therapy and immunotherapy, which are rapidly gaining momentum in the treatment landscape of NSCLC. Different angiogenic and immunosuppressive effects are observed between particle therapy and conventional X-ray radiotherapy. The combination of RE, particle therapy and immunotherapy presents a promising future therapeutic triad for NSCLC.

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Section: Discussion and Concluding Remarksmentioning

confidence: 99%

Recombinant Endostatin as a Potential Radiosensitizer in the Treatment of Non-Small Cell Lung Cancer

et al. 2023

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“…[ 167 ] Despite its significance in lung cancer treatment, the occurrence of radioresistance can diminish the efficacy of radiotherapy, leading to tumor recurrence and metastasis. [ 168 ] Numerous mechanisms have been reported to contribute to the radioresistance of lung cancer, which include the presence of CSCs, existence of the hypoxic TME, cell cycle redistribution, heightened scavenging of ROS, DNA damage repair, dysregulation of microRNAs, occurrence of EMT, and prevention of apoptosis. [ 169 ] Clinical strategies for overcoming radioresistance in lung cancer include: 1) The use of radiosensitizers, such as sodium glycididazole, can effectively boost the sensitivity of hypoxic tumor cells to radiation; [ 170 ] 2) The combination of radiotherapy with chemotherapeutic drugs, such as platinum‐derived drugs, has been shown to enhance DNA damage and inhibit DNA damage repair, thereby improving the efficacy of radiotherapy; [ 171 ] 3) The combination of radiotherapy with molecular targeted drugs, such as EGFR inhibitors, can induce cell cycle arrest and apoptosis, ultimately enhancing the therapeutic effect of radiotherapy; [ 172 ] 4) Alteration in the TME through the administration of angiogenesis inhibitors to inhibit angiogenesis and potentiate the effect of radiotherapy.…”

Section: Emerging Insights Into Drug Resistance In Lung Cancermentioning

confidence: 99%

Nanomedicine Combats Drug Resistance in Lung Cancer

Zheng,

Song,

Zhu

et al. 2023

Advanced Materials

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Lung cancer is the second most prevalent cancer and the leading cause of cancer‐related death worldwide. Surgery, chemotherapy, molecular targeted therapy, immunotherapy and radiotherapy are currently available as treatment methods. However, drug resistance is a significant factor in the failure of lung cancer treatments. Novel therapeutics have been exploited to address complicated resistance mechanisms of lung cancer and the advancement of nanomedicine is extremely promising in terms of overcoming drug resistance. Nanomedicine equipped with multi‐functional and tunable physiochemical properties in alignment with tumor genetic profiles could achieve precise, safe, and effective treatment while minimizing or eradicating drug resistance in cancer. Here, we review the discovered resistance mechanisms for lung cancer chemotherapy, molecular targeted therapy, immunotherapy and radiotherapy, and outline novel strategies for the development of nanomedicine against drug resistance. We focus on engineering design, customized delivery, current challenges and clinical translation of nanomedicine in the application of resistant lung cancer.This article is protected by copyright. All rights reserved

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“…Radiotherapy (RT) is one of the most critical modalities for the treatment of all stages of lung cancer ( 3 ). Despite the significant progress in radiation technology, the overall prognosis of RT for lung cancer remains far from satisfactory ( 4 ). Tumor local and distant relapse after RT is one of the critical contributors to poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Targeting complement C5a to improve radiotherapy sensitivity in non-small cell lung cancer

Yuan¹,

Wang²,

Wu³

et al. 2023

Transl Lung Cancer Res

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Background Tumor local and distant relapse recurrence after radiotherapy (RT) is one of the critical factors leading to poor prognosis. The effective antitumor effects of RT are dependent upon the participation of innate and adaptive components of the immune system. C5a/C5aR1 signaling can regulate antitumor immune effect in the tumor microenvironment (TME). Thus, exploring the changes and mechanism in the TME induced by RT-mediated complement activation may provide a novel perspective for reversing radioresistance. Methods First, fractionated radiation of 8 Gy ×3 fractions were targeted at Lewis lung carcinoma (LLC) tumor-bearing female mice to measure the infiltration of CD8 + T cell and analyze the RNA sequencing (RNA-seq) in RT-recruited CD8 + T cells. Second, tumor growth was measured in LLC tumor-bearing mice treated with RT either with or without C5aR1 inhibitor to clarify the antitumor effect of RT combined with C5aR1 inhibitor. Third, we detected the expression of C5a/C5aR1 and their signaling pathways on radiated tumor tissues. Furthermore, we investigated the expression of C5a in tumor cells at different time points after different doses of RT. Results In our system, RT induced the increased infiltration of CD8 + T cells and local activation of complement C5a/C5aR. Concurrent administration of RT and blocking of C5aR improved radiosensitivity and tumor-specific immune response, which was reflected by high C5aR expression in CD8 + T cells. The AKT/NF-κB pathway was found to be an important signaling pathway in C5a/C5aR axis mediation by RT. Conclusions RT promotes the release of C5a from tumor cells and leads to up-regulation of C5aR1 expression via the AKT/NF-κB pathway. Inhibition of the combination of complement C5a and C5aR could improve RT sensitivity. Our work provides evidence that the combination of RT and C5aR blockade opens a new window of opportunity to promote anti-tumor therapeutic effects in lung cancer.

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Radioresistance of Non-Small Cell Lung Cancers and Therapeutic Perspectives

Cited by 29 publications

References 105 publications

Recombinant Endostatin as a Potential Radiosensitizer in the Treatment of Non-Small Cell Lung Cancer

Recombinant Endostatin as a Potential Radiosensitizer in the Treatment of Non-Small Cell Lung Cancer

Nanomedicine Combats Drug Resistance in Lung Cancer

Targeting complement C5a to improve radiotherapy sensitivity in non-small cell lung cancer

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