Prevention of radiotherapy-induced pro-tumorigenic microenvironment by SFK-inhibitors DOI Creative Commons
Keon Wook Kang, Yong June Choi, Myung Jun Kim

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 9, 2024

Abstract Radiotherapy is a widely employed technique for eradication of tumor using high-energy beams, and has been applied to approximately 50% all solid patients. However, its non-specific, cell-killing property leads inevitable damage surrounding normal tissues. Recent findings suggest that radiotherapy-induced tissue contributes the formation pro-tumorigenic microenvironment. Here, we utilized mouse models uncover mechanisms underlying development such radiation-triggered Radiotherapy-induced stimulates infiltration monocyte-derived macrophages their differentiation into M2 macrophages, ultimately leading fibrosis This phenomenon was consistently observed across two strains organ-targeted radiotherapy models. Notably, SRC family kinases (SFKs) emerged as crucial factors in SFKs activation epithelial cells fibroblasts triggered by direct exposure irradiation or macrophage cytokines. Remarkably, administration SFK-targeted inhibitors reversed myofibroblast activation, effectively ameliorating microenvironment radiated Further, combined significantly enhanced survival tumor-bearing mice. In conclusion, reshaping SFK-targeting potential strategy prevention metastasis recurrence following radiotherapy.

Language: Английский

Therapeutic and diagnostic applications of carbon nanotubes in cancer: recent advances and challenges DOI

Muskan Sharma,

Alessandro Parodi, Sanith Cheriyamundath

et al.

Journal of drug targeting, Journal Year: 2024, Volume and Issue: 32(3), P. 287 - 299

Published: Jan. 22, 2024

Carbon nanotubes (CNTs) are allotropes of carbon, composed carbon atoms forming a tube-like structure. Their high surface area, chemical stability, and rich electronic polyaromatic structure facilitate their drug-carrying capacity. Therefore, CNTs have been intensively explored for several biomedical applications, including as potential treatment option cancer. By incorporating smart fabrication strategies, can be designed to specifically target cancer cells. This targeted drug delivery approach not only maximizes the therapeutic utility but also minimizes any side effects free molecules. utilised photothermal therapy (PTT) which uses photosensitizers generate reactive oxygen species (ROS) kill cells, in immunotherapeutic applications. Regarding latter, example, CNT-based formulations preferentially intra-tumoural regulatory T-cells. act efficient antigen presenters. With capabilities photoacoustic, fluorescent Raman imaging, excellent diagnostic tools well. Further, metallic nanoparticles, such gold or silver combined with create nanobiosensors measure biological reactions. review focuses on current knowledge about theranostic CNT, challenges associated large-scale production, possible important parameters consider when exploring clinical usage.

Language: Английский

Citations

11
Dickkopf-1 promotes tumor progression of gefitinib- resistant non-small cell lung cancer through cancer cell-fibroblast interactions DOI Creative Commons
Munkyung Choi, Yong June Choi, Young Ju Lee

et al.

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 1, 2025

Abstract Background Cancer cell-secreted proteins play a critical role in tumor progression and chemoresistance by influencing intercellular interactions within the microenvironment. Investigating intratumoral functions of these secretory may provide insights into understanding treating chemoresistant cancers. This study aims to identify potential anticancer target(s) gefitinib-resistant non-small cell lung cancer (NSCLC), with focus on their effects interactions. Methods Differentially expressed were identified human NSCLC lines (PC9-GR HCC827-GR), revealing an elevation Dickkopf-1 (DKK1) expression secretion. To elucidate DKK1 cancer, neutralizing antibody against evaluated tumors comprising either cells alone or co-injected fibroblasts (MRC-5). Following confirmation importance cell-fibroblast protumorigenic activity DKK1, fibroblast traits modulated further analyzed. Results Gefitinib-resistant exhibited increased protein expression. Although elevated levels linked poor prognosis, did not directly affect proliferation. However, blockade showed significant containing fibroblasts, suggesting that DKK1’s pro-tumorigenic roles are mediated through altered characteristics, enhancing inflammatory while diminishing myofibroblast These DKK1-induced changes via activation c-JUN pathway fibroblasts. Moreover, was as target across various types beyond cancer. Conclusions clarifies mediates between contributing progression. Therefore, we propose promising for treatment NSCLC.

Language: Английский

Citations

0
Emerging roles of small extracellular vesicles in metabolic reprogramming and drug resistance in cancers DOI Open Access

Jingcun Shi,

Ying Shen, Jianjun Zhang

et al.

Cancer Drug Resistance, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 27, 2024

Studies of carcinogenic metabolism have shown that cancer cells significant metabolic adaptability and their dynamics undergo extensive reprogramming, which is a fundamental feature cancer. The Warburg effect describes the preference for glycolysis over oxidative phosphorylation (OXPHOS), even under aerobic conditions. However, reprogramming in involves not only but also changes lipid amino acid metabolism. mechanisms these shifts are critical discovery novel therapeutic targets. Despite advances field oncology, chemotherapy resistance, including multidrug remains challenge. Research has revealed correlation between anticancer drug underlying complex fully understood. In addition, small extracellular vesicles (sEVs) may play role expanding promoting development resistance by mediating intercellular communication. aim this review to assess processes intersect with therapy, particular attention given glycolysis, metabolism, accompany phenomenon. sEVs disseminating drug-resistant phenotypes will be critically evaluated.

Language: Английский

Citations

2
Prevention of radiotherapy-induced pro-tumorigenic microenvironment by SFK-inhibitors DOI Creative Commons
Keon Wook Kang, Yong June Choi, Myung Jun Kim

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 9, 2024

Abstract Radiotherapy is a widely employed technique for eradication of tumor using high-energy beams, and has been applied to approximately 50% all solid patients. However, its non-specific, cell-killing property leads inevitable damage surrounding normal tissues. Recent findings suggest that radiotherapy-induced tissue contributes the formation pro-tumorigenic microenvironment. Here, we utilized mouse models uncover mechanisms underlying development such radiation-triggered Radiotherapy-induced stimulates infiltration monocyte-derived macrophages their differentiation into M2 macrophages, ultimately leading fibrosis This phenomenon was consistently observed across two strains organ-targeted radiotherapy models. Notably, SRC family kinases (SFKs) emerged as crucial factors in SFKs activation epithelial cells fibroblasts triggered by direct exposure irradiation or macrophage cytokines. Remarkably, administration SFK-targeted inhibitors reversed myofibroblast activation, effectively ameliorating microenvironment radiated Further, combined significantly enhanced survival tumor-bearing mice. In conclusion, reshaping SFK-targeting potential strategy prevention metastasis recurrence following radiotherapy.

Language: Английский

Citations

0