Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance

Frontiers in Molecular Biosciences, Journal Year: 2020, Volume and Issue: 7

Published: Aug. 20, 2020

Nanotechnology has been extensively studied and exploited for cancer treatment as the important role of nanoparticles in drug delivery system. Compared with conventional drugs, nanoparticle-based specific advantages, including good stability, biocompatibility, enhancing permeability retention effect precise targeting. In addition, nanoparticle drugs have also shown a certain overcoming resistance cancer. The application development hybrid combined properties different lead this type drug-carrier system to further step. review, we discuss delivery, describe targeting mechanism well its function on reversing resistance.

Language: Английский

---

Current trends and challenges in cancer management and therapy using designer nanomaterials

Nano Convergence, Journal Year: 2019, Volume and Issue: 6(1)

Published: July 14, 2019

Nanotechnology has the potential to circumvent several drawbacks of conventional therapeutic formulations. In fact, significant strides have been made towards application engineered nanomaterials for treatment cancer with high specificity, sensitivity and efficacy. Tailor-made functionalized specific ligands can target cells in a predictable manner deliver encapsulated payloads effectively. Moreover, also be designed increased drug loading, improved half-life body, controlled release, selective distribution by modifying their composition, size, morphology, surface chemistry. To date, polymeric nanomaterials, metallic nanoparticles, carbon-based materials, liposomes, dendrimers developed as smart delivery systems treatment, demonstrating enhanced pharmacokinetic pharmacodynamic profiles over formulations due nanoscale size unique physicochemical characteristics. The data present literature suggest that nanotechnology will provide next-generation platforms management anticancer therapy. Therefore, this critical review, we summarize range which are currently being employed therapies discuss fundamental role properties management. We further elaborate on topical progress date toward nanomaterial engineering therapy, including current strategies targeting release efficient administration. issues nanotoxicity, is an often-neglected feature nanotechnology. Finally, attempt challenges nanotherapeutics outlook future important field.

Language: Английский

---

Cell adhesion in cancer: Beyond the migration of single cells

Journal of Biological Chemistry, Journal Year: 2020, Volume and Issue: 295(8), P. 2495 - 2505

Published: Jan. 14, 2020

Homeostasis in healthy tissues strongly relies on cell-to-cell adhesion and cell-to-extracellular matrix interactions. For instance, normal epithelial cells maintain tissue structure by adhering to each other the extracellular matrix. The proteins that mediate these distinct interactions are collectively called cell molecules divided into four major groups: cadherins, integrins, selectins, immunoglobulins. They not only physically anchor cells, but also critically integrate signaling between microenvironment cells. These signals include biochemical cues, as can both act ligand-activated receptors activate mechanotransduction triggered changes physical environment. Molecular mechanisms related have been extensively studied, especially because mutations expression of proteins, particularly cadherins frequently associated with diseases ranging from developmental intellectual disability cancer. In fact, two hallmarks cancer, loss anchorage-independent growth, dependent molecules. Despite many studies elucidating relationships malignant transformation metastasis cellular processes, several areas still await exploration. Here, we highlight recently discovered roles collective cancer migration discuss utility three-dimensional models studying cell-cell adhesion. We describe recent therapeutic approaches targeting

Language: Английский

---

Clinical update on head and neck cancer: molecular biology and ongoing challenges

Cell Death and Disease, Journal Year: 2019, Volume and Issue: 10(8)

Published: July 15, 2019

Abstract Head and neck squamous cell carcinomas (HNSCCs) are an aggressive, genetically complex difficult to treat group of cancers. In lieu truly effective targeted therapies, surgery radiotherapy represent the primary treatment options for most patients. But these treatments associated with significant morbidity a reduction in quality life. Resistance both only available therapy, subsequent relapse common. Research has therefore focussed on identifying biomarkers stratify patients into clinically meaningful groups develop more therapies. However, as we now discovering, poor response therapy aggressive nature HNSCCs is not affected by alterations intracellular signalling pathways but also heavily influenced behaviour extracellular microenvironment. The HNSCC tumour landscape environment permissive tumours’ nature, fostered actions immune system, hypoxia influence microbiome. Solving challenges rests expanding our knowledge areas, parallel greater understanding molecular biology subtypes. This update aims build earlier 2014 review bringing up date provide insights areas ongoing research perspectives future.

Language: Английский

---

Multidrug Resistance in Cancer: Understanding Molecular Mechanisms, Immunoprevention and Therapeutic Approaches

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: June 23, 2022

Cancer is one of the leading causes death worldwide. Several treatments are available for cancer treatment, but many treatment methods ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions This review describes known MDR mechanisms in cells and discusses ongoing laboratory approaches novel strategies that aim inhibit, circumvent, or reverse development various types. In this review, we discuss both intrinsic acquired drug resistance, addition highlighting hypoxia- autophagy-mediated mechanisms. factors, including individual genetic differences, such as mutations, altered epigenetics, enhanced efflux, cell inhibition, other molecular cellular mechanisms, responsible anticancer agents. Drug can also depend on autophagic hypoxic status. The expression drug-resistant genes regulatory determine discussed. Methods circumvent MDR, immunoprevention, use microparticles nanomedicine might result better fighting

Language: Английский

---

Proteomic analyses of ECM during pancreatic ductal adenocarcinoma progression reveal different contributions by tumor and stromal cells

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(39), P. 19609 - 19618

Published: Sept. 4, 2019

Pancreatic ductal adenocarcinoma (PDAC) has prominent extracellular matrix (ECM) that compromises treatments yet cannot be nonselectively disrupted without adverse consequences. ECM of PDAC, despite the recognition its importance, not been comprehensively studied in patients. In this study, we used quantitative mass spectrometry (MS)-based proteomics to characterize proteins normal pancreas and pancreatic intraepithelial neoplasia (PanIN)- PDAC-bearing from both human patients mouse genetic models, as well chronic pancreatitis patient samples. We describe detailed changes abundance complexity matrisome course PDAC progression. reveal an early up-regulated group PanIN, which are further uncover notable similarities between PDAC. assigned cellular origins by performing MS on multiple lines human-to-mouse xenograft tumors. found that, although stromal cells produce over 90% mass, elevated levels derived tumor cells, but those produced exclusively tend correlate with poor survival. Furthermore, distinct pathways were implicated regulating expression cancer cells. suggest rather than global suppression production, more precise manipulations, such targeting tumor-promoting their regulators could effective therapeutically.

Language: Английский

---

Alliance with EPR Effect: Combined Strategies to Improve the EPR Effect in the Tumor Microenvironment

Theranostics, Journal Year: 2019, Volume and Issue: 9(26), P. 8073 - 8090

Published: Jan. 1, 2019

The use of nanomedicine for cancer treatment takes advantage its preferential accumulation in tumors owing to the enhanced permeability and retention (EPR) effect.The development has promised highly effective options unprecedented by standard therapeutics.However, therapeutic efficacy passively targeted is not always satisfactory because it largely influenced heterogeneity intensity EPR effect exhibited within a tumor, at different stages among individual tumors.In addition, limited data on effectiveness human hinders further clinical translation nanomedicine.This unsatisfactory outcome mice humans necessitates novel approaches improve effect.This review focuses current attempts overcoming limitations traditional EPR-dependent incorporating supplementary strategies, such as additional molecular targeting, physical alteration, or physiological remodeling tumor microenvironment.This will provide valuable insight researchers who seek overcome relying alone go "beyond effect".

Language: Английский

---

Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(3), P. 361 - 379.e16

Published: Jan. 9, 2021

We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins phosphosites, prioritizes copy number drivers, highlights an oncogenic role for RNA processing genes. investigation mutual exclusivity between FAT1 truncating mutations 11q13.3 amplifications reveals dysregulated actin dynamics as common functional consequence. Phosphoproteomics characterizes two modes EGFR activation, suggesting new strategy to stratify HNSCCs based on ligand abundance effective treatment with inhibitory monoclonal antibodies. Widespread deletion immune modulatory genes accounts low infiltration in immune-cold tumors, whereas concordant upregulation multiple checkpoint may underlie resistance anti-programmed death protein 1 monotherapy immune-hot tumors. Multi-omic identifies three molecular subtypes high potential CDK inhibitors, anti-EGFR antibody therapy, immunotherapy, respectively. Altogether, proteogenomics provides systematic framework inform HNSCC biology treatment.

Language: Английский

---

Oral squamous cell carcinomas: state of the field and emerging directions

International Journal of Oral Science, Journal Year: 2023, Volume and Issue: 15(1)

Published: Sept. 22, 2023

Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of oral cavity. It accounts for approximately 90% malignancies and impairs appearance, pronunciation, swallowing, flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to Global Cancer Observatory (GCO), incidence will rise by 40% 2040, accompanied a growth in mortality. Persistent exposure various risk factors, including tobacco, alcohol, betel quid (BQ), human papillomavirus (HPV), lead development potentially malignant disorders (OPMDs), which are lesions with an increased developing into OSCC. Complex multifactorial, oncogenesis process involves genetic alteration, epigenetic modification, dysregulated tumor microenvironment. Although therapeutic interventions, such as chemotherapy, radiation, immunotherapy, nanomedicine, have been proposed prevent or treat OPMDs, understanding mechanism facilitate identification prognostic thereby improving efficacy treatment patients. This review summarizes mechanisms involved Moreover, current interventions methods OPMDs discussed comprehension provide several prospective outlooks fields.

Language: Английский

---

Advances in covalent kinase inhibitors

Chemical Society Reviews, Journal Year: 2020, Volume and Issue: 49(9), P. 2617 - 2687

Published: Jan. 1, 2020

Over the past decade, covalent kinase inhibitors (CKI) have seen a resurgence in drug discovery. Covalency affords unique set of advantages as well challenges relative to their non-covalent counterpart. After reversible protein target recognition and binding, irreversibly modify proximal nucleophilic residue on via reaction with an electrophile. To date, acrylamide group remains predominantly employed electrophile CKI development, its incorporation majority clinical candidates FDA approved therapies. Nonetheless, recent years considerable efforts ensued characterize alternative electrophiles that exhibit irreversible or reversibly binding mechanisms towards cysteine thiols other amino acids. This review article provides comprehensive overview CKIs reported literature over decade period, 2007-2018. Emphasis is placed rationale behind warhead choice, optimization approach, inhibitor design. Current are also highlighted, addition detailed analysis common trends themes observed within listed data set.

Language: Английский

---