In Response to Precision Medicine: Current Subcellular Targeting Strategies for Cancer Therapy

Advanced Materials, Journal Year: 2022, Volume and Issue: 35(21)

Published: Nov. 29, 2022

Abstract Emerging as a potent anticancer treatment, subcellular targeted cancer therapy has drawn increasing attention, bringing great opportunities for clinical application. Here, two targeting strategies four main organelles (mitochondria, lysosome, endoplasmic reticulum, and nucleus), including molecule‐ nanomaterial (inorganic nanoparticles, micelles, organic polymers, others)‐based delivery or therapeutic strategies, are summarized. Phototherapy, chemotherapy, radiotherapy, immunotherapy, “all‐in‐one” combination among the covered in detail. Such materials constructed based on specific properties relevant mechanisms of organelles, enabling elimination tumors by inducing dysfunction corresponding destroying structures. The challenges faced organelle‐targeting therapies also Looking forward, paradigm with enhanced efficacy compared to current approaches is envisioned.

Language: Английский

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Targeting the ERK1/2 and p38 MAPK pathways attenuates Golgi tethering factor golgin-97 depletion-induced cancer progression in breast cancer

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 13, 2025

The Golgi apparatus is widely considered a secretory center and hub for different signaling pathways. Abnormalities in dynamics can perturb the tumor microenvironment influence cell migration. Therefore, unraveling regulatory network of searching pharmacological targets would facilitate development novel anticancer therapies. Previously, we reported an unconventional role tethering factor golgin-97 inhibiting breast motility, its downregulation was associated with poor patient prognosis. However, specific mechanism cancer progression vivo remain unclear. We integrated genetic knockout (KO) golgin-97, animal models (zebrafish xenograft mice), multi-omics analysis (next-generation sequencing proteomics), bioinformatics analysis, kinase inhibitor treatment to evaluate effects KO triple-negative cells. Gene knockdown followed by qRT‒PCR, Western blotting, viability, migration, cytotoxicity assays were performed elucidate mechanisms KO-mediated invasion. A mouse model used investigate drug therapy. demonstrated that promoted metastasis zebrafish models. Multi-omics revealed Wnt pathway, MAPK cascades, inflammatory cytokines are involved KO-induced progression. Targeting ERK1/2 p38 pathways effectively attenuated golgin-97-induced reduced expression mediators, enhanced chemotherapeutic effect paclitaxel vitro vivo. Specifically, compared regimen, combination inhibitors significantly prevented lung injury. further hypoxia physiological condition reduces cancer, revealing potential feedback loop between ERK/MAPK golgin-97. Our results collectively support microenvironment, possibly providing new insights anti-breast development.

Language: Английский

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Functional Materials for Subcellular Targeting Strategies in Cancer Therapy: Progress and Prospects

Advanced Materials, Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 4, 2023

Neoadjuvant and adjuvant therapies have made significant progress in cancer treatment. However, tumor therapy still faces challenges due to the intrinsic heterogeneity of cancer, genomic instability, formation an immunosuppressive microenvironment. Functional materials possess unique biological properties such as long circulation times, tumor-specific targeting, immunomodulation. The combination functional with natural substances nanotechnology has led development smart biomaterials multiple functions, high biocompatibilities, negligible immunogenicities, which can be used for precise Recently, subcellular structure-targeting received particular attention various biomedical applications including diagnosis, sensing, imaging tumors drug delivery. Subcellular organelle-targeting precisely accumulate therapeutic agents organelles, considerably reduce threshold dosages agents, minimize drug-related side effects. This review provides a systematic comprehensive overview research organelle-targeted based on nanomaterials. Moreover, it explains prospects precision oncology. will serve excellent cutting-edge guide researchers field therapy.

Language: Английский

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Cascade Delivery to Golgi Apparatus and On‐Site Formation of Subcellular Drug Reservoir for Cancer Metastasis Suppression

Small, Journal Year: 2022, Volume and Issue: 19(11)

Published: Dec. 30, 2022

As the foremost cause of cancer-related death, metastasis consists three steps: invasion, circulation, and colonization. Only targeting one single phase cascade may be insufficient since there are many alternative routes for tumor cells to disseminate. Here, target whole metastasis, hybrid erythrocyte cell membrane-coated nanoparticle (Hyb-NP) is designed with dual functions increasing circulation time recognizing primary, circulating, colonized tumors. After loading monensin, a recently reported inhibitor, delivery system profoundly reduces spontaneous in an orthotopic breast cancer model. Underlying mechanism studies reveal that Hyb-NP can deliver monensin its action site Golgi apparatus, return, block exocytosis from forming reservoir-like subcellular structure. Notably, apparatus reservoir displays vital suppressing initialization, including enhanced drug retention, metastasis-related cytokine release inhibition, directional migration inhibition. Collectively, based on at tissue level, further formation level provides potential therapeutic strategy suppression.

Language: Английский

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Golgi Stress Response: New Insights into the Pathogenesis and Therapeutic Targets of Human Diseases

Molecules and Cells, Journal Year: 2022, Volume and Issue: 46(4), P. 191 - 199

Published: Dec. 28, 2022

The Golgi apparatus modifies and transports secretory membrane proteins. In some instances, the production of proteins exceeds capacity apparatus, including vesicle trafficking post-translational modification macromolecules. These are not modified or delivered appropriately due to insufficiency in function. conditions disturb homeostasis induce a cellular condition known as stress, causing cells activate 'Golgi stress response,' which is homeostatic process increase based on requirements. Since functions diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, PERK regulate each function separately. Understanding crucial for revealing mechanisms underlying dynamics its effect human health because many signaling molecules related diseases, ranging from viral infections fatal neurodegenerative diseases. Therefore, it valuable summarize investigate disease pathogenesis, they may contribute developing novel therapeutic strategies. this review, we perturbations Golgi, well potentials new strategies treating stress-associated

Language: Английский

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EMT-activated secretory and endocytic vesicular trafficking programs underlie a vulnerability to PI4K2A antagonism in lung cancer

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(7)

Published: Feb. 9, 2023

Hypersecretory malignant cells underlie therapeutic resistance, metastasis, and poor clinical outcomes. However, the molecular basis for hypersecretion remains obscure. Here, we showed that epithelial-mesenchymal transition (EMT) initiates exocytic endocytic vesicular trafficking programs in lung cancer. The EMT-activating transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) executed a PI4KIIIβ-to-PI4KIIα (PI4K2A) dependency switch drove PI4P synthesis Golgi endosomes. EMT enhanced vulnerability of cancer to PI4K2A small-molecule antagonists. formed MYOIIA-containing protein complex facilitated secretory vesicle biogenesis Golgi, thereby establishing hypersecretory state involving osteopontin (SPP1) other prometastatic ligands. In endosomal compartment, accelerated recycling SPP1 receptors complete an SPP1-dependent autocrine loop interacted with HSP90 prevent lysosomal degradation AXL receptor tyrosine kinase, driver cell migration. These results show coordinates establish therapeutically actionable drives progression.

Language: Английский

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A Golgi‐Targeted Platinum Complex Plays a Dual Role in Autophagy Regulation for Highly Efficient Cancer Therapy

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(44)

Published: Sept. 15, 2023

Regulating autophagy to control the homeostatic recycling process of cancer cells is a promising anticancer strategy. Golgi apparatus substrate but Golgi-autophagy (Golgiphagy) mediated antitumor pathway rarely reported. Herein, we have developed novel Golgi-targeted platinum (II) complex Pt3, which ca. 20 times more cytotoxic lung carcinoma than cisplatin and can completely eliminate tumors after intratumoral administration in vivo. Its nano-encapsulated system for tail vein also features good anti-tumor effect. Mechanism studies indicate that Pt3 induces substantial stress, indicated by fragmentation structure, down-regulation proteins (GM130, GRASP65/55), loss Golgi-dependent transport glycosylation. This triggers Golgiphagy blocks subsequent fusion autophagosomes with lysosomes, dual role regulation, resulting proteostasis apoptotic cell death. As far as know, first Pt trigger stress-mediated dual-regulation autophagic flux autophagy-apoptosis crosstalk highly efficient therapy.

Language: Английский

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Glycoprofiling of proteins as prostate cancer biomarkers: A multinational population study

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(3), P. e0300430 - e0300430

Published: March 18, 2024

The glycoprofiling of two proteins, the free form prostate-specific antigen (fPSA) and zinc-α-2-glycoprotein (ZA2G), was assessed to determine their suitability as prostate cancer (PCa) biomarkers. proteins performed by analysing changes in glycan composition on fPSA ZA2G using lectins (proteins that recognise glycans, i . e complex carbohydrates). specific magnetic beads (MBs) modified with horseradish peroxidase (HRP) antibodies selectively enriched or from human serum samples. Subsequently, antibody-captured glycoproteins were incubated lectin-coated ELISA plates. In addition, a novel glycoprotein standard (GPS) used normalise assay. samples obtained men undergoing biopsy after an elevated PSA, patients without prior therapy. results are presented ROC (Receiver Operating Curve). A DCA (Decision Curve Analysis) evaluate clinical performance net benefit glycan-based biomarkers also performed. While showed little promise potential PCa biomarker, would appear have significant potential. Hence, GIA (Glycobiopsy ImmunoAssay) test integrates ( forms fPSA). could be for early diagnoses (AUC = 0.83; n 559 samples) use therapy-monitoring 0.90; 176 samples). Moreover, analysis subset (n 215) revealed 0.81) outperformed PHI (Prostate Health Index) 0.69) discriminating between those benign PSA elevation.

Language: Английский

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Golgi apparatus targeted therapy in cancer: Are we there yet?

Life Sciences, Journal Year: 2024, Volume and Issue: 352, P. 122868 - 122868

Published: June 25, 2024

Language: Английский

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The role of Golgi complex proteins in cell division and consequences of their dysregulation

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 7, 2025

The GC (Golgi complex) plays a pivotal role in the trafficking and sorting of proteins lipids until they reach their final destination. Additionally, acts as signalling hub to regulate multitude cellular processes, including cell polarity, motility, apoptosis, DNA repair division. In light these crucial roles, has garnered increasing attention, particularly given evidence that dysregulation GC-regulated pathways may contribute onset various pathological conditions. This review examines functions GC-localised regulating cycle progression, both mitosis meiosis. It reviews involvement GC-resident formation orientation spindle during roles played by controlling division, this also addresses cancer development. Furthermore, TCGA (The Cancer Genome Atlas) database been queried order retrieve information on genetic alterations correlation between expression survival patients. data presented highlight relevance differentiation tumourigenesis.

Language: Английский

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