PLK4 inhibition as a strategy to enhance non-small cell lung cancer radiosensitivity DOI Open Access
Irma G. Domínguez-Vigil, Kishore Banik, Marta Baro

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 23, 2025

Abstract Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell lung (NSCLC) most common subtype and comprises 85% cases. Despite treatment advances, local control after curative-intent chemoradiation for NSCLC remains suboptimal. Polo-like kinase 4 (PLK4) a serine-threonine that plays critical role in regulation centrosome duplication cycle progression overexpressed NSCLC, thus, making it potential therapeutic target. CFI-400945 an orally available PLK4 inhibitor currently undergoing clinical trial evaluation. As radiation causes death primarily by mitotic catastrophe, process enhanced alterations amplification, we hypothesized disruption machinery inhibition would enhance effects NSCLC. resulted radiosensitization lines. In contrast, had no effect on radiosensitivity normal fibroblasts. did not affect cell-cycle phase distribution prior to radiation, but rather combination increased G2/M arrest, concomitant increase through catastrophe. Lastly, radiation-induced tumor growth delay xenografts. These data indicate targeting novel approach sensitivity vitro vivo potentiation amplification

Language: Английский

Superparamagnetic Iron Oxide Nanoparticles (SPION): From Fundamentals to State-of-the-Art Innovative Applications for Cancer Therapy DOI Creative Commons
Thomas Vangijzegem, Valentin Lecomte,

Indiana Ternad

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(1), P. 236 - 236

Published: Jan. 10, 2023

Despite significant advances in cancer therapy over the years, its complex pathological process still represents a major health challenge when seeking effective treatment and improved healthcare. With advent of nanotechnologies, nanomedicine-based has been widely explored as promising technology able to handle requirements clinical sector. Superparamagnetic iron oxide nanoparticles (SPION) have at forefront nanotechnology development since mid-1990s, thanks their former role contrast agents for magnetic resonance imaging. Though use MRI probes discontinued due an unfavorable cost/benefit ratio, several innovative applications therapeutic tools prompted renewal interest. The unique characteristics SPION, i.e., properties enabling specific response submitted high frequency (magnetic hyperthermia) or low (magneto-mechanical therapy) alternating field, ability generate reactive oxygen species (either intrinsically activated using various stimuli), make them particularly adapted therapy. This review provides comprehensive description fundamental aspects SPION formulation highlights recent approaches regarding vivo field

Language: Английский

Citations

96
Metabolic Intervention Liposome Boosted Lung Cancer Radio‐Immunotherapy via Hypoxia Amelioration and PD‐L1 Restraint DOI Creative Commons

Saijun Wang,

Zaigang Zhou, Rui Hu

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(18)

Published: April 24, 2023

At present, radiotherapy (RT) still acquires limited success in clinical due to the lessened DNA damage under hypoxia and acquired immune tolerance owing amplified programmed death ligand-1 (PD-L1) expression. Incredibly, intracellular PD-L1 expression depression is proven better sensitize RT by inhibiting repair. However, disability of clinically used antibodies disrupting extracellular PD-L1function limits effectiveness radio-immunotherapy. Therefore, regulation strategies are urgently needed Hence, for this purpose, TPP-LND synthesized linking mitochondrial-targeted triphenylphosphine cations (TPP+ ) antineoplastic agent lonidamine (LND), which significantly reduces dose LND induce effective oxidative phosphorylation inhibition (2 vs 300 µM). Then, wrapped with liposomes form TPP-LND@Lip nanoparticles. By doing this, nanoparticles can reversing hypoxic microenvironment tumors generate more reducing via enhancing adenosine 5'-monophosphate-activated protein kinase activation. As expected, these well-designed economical than conventional anti-PD-L1 some extent.

Language: Английский

Citations

48
Recent advances in the metal/organic hybrid nanomaterials for cancer theranostics DOI
Zhaoyi Ye, Ying Bao, Zefeng Chen

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 504, P. 215654 - 215654

Published: Jan. 20, 2024

Language: Английский

Citations

18
Review of Deep Learning Based Automatic Segmentation for Lung Cancer Radiotherapy DOI Creative Commons
Xi Liu,

Kai-Wen Li,

Ruijie Yang

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: July 8, 2021

Lung cancer is the leading cause of cancer-related mortality for males and females. Radiation therapy (RT) one primary treatment modalities lung cancer. While delivering prescribed dose to tumor targets, it essential spare tissues near targets—the so-called organs-at-risk (OARs). An optimal RT planning benefits from accurate segmentation gross volume surrounding OARs. Manual a time-consuming tedious task radiation oncologists. Therefore, crucial develop automatic image relieve oncologists contouring work. Currently, atlas-based technique commonly used in clinical routines. However, this depends heavily on similarity between atlas segmented. With significant advances made computer vision, deep learning as part artificial intelligence attracts increasing attention medical segmentation. In article, we reviewed based techniques related compared them with technique. At present, auto-segmentation OARs relatively large such heart etc. outperforms organs small esophagus. The average Dice coefficient (DSC) lung, liver are over 0.9, best DSC spinal cord reaches 0.9. esophagus ranges 0.71 0.87 ragged performance. terms volume, below 0.8. Although indicate superiority many aspects manual segmentation, various issues still need be solved. We discussed potential including low contrast, dataset size, consensus guidelines, network design. Clinical limitations future research directions were well.

Language: Английский

Citations

77
Developing a Copper(II) Agent Based on His-146 and His-242 Residues of Human Serum Albumin Nanoparticles: Integration To Overcome Cisplatin Resistance and Inhibit the Metastasis of Nonsmall Cell Lung Cancer DOI
Ming Jiang, Zhenlei Zhang, Wenjuan Li

et al.

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(13), P. 9447 - 9458

Published: July 4, 2022

To overcome the resistance of nonsmall cell lung cancer (NSCLC) cells to cisplatin and inhibit their metastasis, we proposed develop a Cu(II) agent based on specific residue(s) HSA nanoparticles (NPs) for multitargeting tumor microenvironment (TME). this end, not only synthesized four 2-hydroxy-3-methoxybenzaldehyde thiosemicarbazone compounds (C1–C4), obtaining Cu compound (C4) with significant cytotoxicity by studying structure–activity relationships, but also revealed binding mechanism C4 through X-ray crystallography confirmed successful construction new HSA-C4 NPs delivery system. inhibited A549cisR growth optimized anticancer behavior C4. We further C4/HSA-C4 NP TME resistance: killing acting mtDNA inducing apoptosis, polarizing M2-type macrophages M1-type, inhibiting angiogenesis.

Language: Английский

Citations

44
Polypeptides from traditional Chinese medicine: Comprehensive review of perspective towards cancer management DOI

Zhuolin Jia,

Xiaoli Zhu,

Ye Zhou

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 260, P. 129423 - 129423

Published: Jan. 15, 2024

Language: Английский

Citations

10
Synergistic effect of cannabidiol with dasatinib on lung cancer by SRC/PI3K/AKT signal pathway DOI Open Access

Qianqian Ye,

C. Gui, Di Jin

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116445 - 116445

Published: March 18, 2024

Dasatinib-related resistance frequently occurs and may lead to the failure of chemotherapy; thus, dose interruptions are necessary. Cannabidiol (CBD) has potential for integration with orthodox cancer care. In this study, we explored combination effect CBD dasatinib on A549 cells. in could induce significant synergistic apoptosis vitro (ZIP > 10) vivo. The low-dose exhibited antiproliferative proapoptotic effects through up-regulation caspase-3 Bax, down-regulation Bcl-2 xenograft mouse model suggested that was more efficient safer. short, a anticancer by targeting SRC/PI3K/AKT signaling pathway, suggesting therapeutic option treatment lung cancer.

Language: Английский

Citations

8
Enhancing Targeted Cancer Treatment by Combining Hyperthermia and Radiotherapy Using Mn–Zn Ferrite Magnetic Nanoparticles DOI

Yijue Wang,

Liqing Zou,

Zhe Qiang

et al.

ACS Biomaterials Science & Engineering, Journal Year: 2020, Volume and Issue: 6(6), P. 3550 - 3562

Published: April 29, 2020

Radiotherapy (RT) is a major treatment method for non-small-cell lung cancer (NSCLC), and development of new modality now critical to amplify the negative effects RT on tumors. In this study, we demonstrated nanoparticle-loaded block copolymer micellar system hyperthermia (HT) that can be used synergistic therapy under alternating magnetic field (AMF) radiation field. Block micelles (polyethylene glycol-block-polycaprolactone, or PEG-PCL) containing hyaluronic acid (HA) Mn–Zn ferrite nanoparticles (MZF) were fabricated via two-step preparation. HA-modified (MZF-HA) enriched in CD44 highly expressing tumor cells, such as A549 (human adenocarcinoma cell line), through an active targeting mechanism receptor–ligand binding HA (HA receptor). MZF generate thermal energy AMF, leading local temperature increase approximately 43 °C at sites mild HT, increased oxygenation enhance therapeutic effect RT. vitro experiments show MZF-HA able achieve excellent specific performance toward cells with biocompatibility well enhanced HT by apoptosis flow cytometry. subcutaneous xenografts model, MRI confirms enrichment tumor, hypoxia immunohistochemistry analysis (IHC) proved after HT. Furthermore, volume decreases 49.6% combination comparison 58.8% untreated group. These results suggest application further clinical NSCLC evaluation.

Language: Английский

Citations

56
Up-regulation of VANGL1 by IGF2BPs and miR-29b-3p attenuates the detrimental effect of irradiation on lung adenocarcinoma DOI Creative Commons

Chuncheng Hao,

Cui‐yang Xu,

Xinyu Zhao

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2020, Volume and Issue: 39(1)

Published: Nov. 23, 2020

Abstract Accumulating evidence suggests that radiation treatment causes an adaptive response of lung adenocarcinoma (LUAD), which in turn attenuates the lethal effect irradiation. Previous microarray assays manifested change gene expression profile after Bioinformatics analysis significantly changed genes revealed VANGL1 may notably influence on LUAD. To determine role VANGL1, this study knocked down or overexpressed M6A level mRNA was determined by M6A-IP-qPCR assay. Irradiation caused up-regulation with increase m6A level. Depletion readers, IGF2BP2/3, undermined stability and upon miR-29b-3p decreased irradiation, however is a target identified Luciferase report The reduction inhibited degradation mRNA. Knockdown enhanced detrimental irradiation LUAD, as indicated more severe DNA damage increased percentage apoptotic cells. Immunocoprecipitation interaction between BRAF. BRAF probably through suppressing protein degradation, led to downstream effectors, TP53BP1 RAD51. These effectors are involved repair damage. In summary, which, turn, mitigated LUAD protecting from activating BRAF/TP53BP1/RAD51 cascades. Increased reduced took responsibility overexpression

Language: Английский

Citations

54
Tumor-associated macrophages in non-small-cell lung cancer: From treatment resistance mechanisms to therapeutic targets DOI Creative Commons
Zhenjun Huang,

Ziqi Xiao,

Li‐Qing Yu

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 196, P. 104284 - 104284

Published: Feb. 2, 2024

Non-small cell lung cancer (NSCLC) remains one of the leading causes cancer-related deaths worldwide. Different treatment approaches are typically employed based on stage NSCLC. Common clinical methods include surgical resection, drug therapy, and radiation therapy. However, with introduction utilization immune checkpoint inhibitors, has entered a new era, completely revolutionizing landscape for various cancers significantly improving overall patient survival. Concurrently, resistance often poses critical challenge, many patients experiencing disease progression following an initial response due to resistance. Increasing evidence suggests that tumor microenvironment (TME) plays pivotal role in Tumor-associated macrophages (TAMs) within TME can promote NSCLC by secreting cytokines activating signaling pathways, interacting other cells. Therefore, this article will focus elucidating key mechanisms TAMs analyze how targeting reduce levels NSCLC, providing comprehensive understanding principles overcome

Language: Английский

Citations

6