Bioorganic & Medicinal Chemistry, Год журнала: 2023, Номер 90, С. 117367 - 117367
Опубликована: Июнь 10, 2023
Язык: Английский
Journal of Advanced Research, Год журнала: 2023, Номер 54, С. 271 - 292
Опубликована: Фев. 14, 2023
Triple-negative breast cancer (TNBC) is a heterogeneous, aggressive phenotype of with associated chemoresistance. The development chemo- or radioresistance could be attributed to diverse tumor microenvironments, overexpression membrane proteins (transporters), epigenetic changes, and alteration the cell signaling pathways/genes stem cells (CSCs). Due heterogeneous nature TNBC, therapeutic response existing modalities offers limited scope thus results in reccurance after therapy. To establish landmark efficacy, number novel have been proposed. In addition, reversal resistance that developed during treatment may altered by employing appropriate modalities. This review aims discuss plethora investigations carried out, which will help readers understand make an choice therapy directed toward complete elimination TNBC. manuscript addresses major contributory factors from microenvironment are responsible for chemoresistance poor prognosis. cellular events molecular mechanism-based interventions explained detail. Inhibition ABC transporters, pathways CSCs, modification promising this regard. TNBC progression, invasion, metastasis recurrence can also inhibited blocking multiple pathways, targeting specific receptors/epigenetic targets, disrupting bioenergetics generating reactive oxygen species (ROS).
Язык: Английский
Процитировано
59
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(15), С. 12222 - 12222
Опубликована: Июль 30, 2023
One of the leading causes death worldwide, in both men and women, is cancer. Despite significant development therapeutic strategies, inevitable emergence drug resistance limits success impedes curative outcome. Intrinsic acquired are common mechanisms responsible for cancer relapse. Several factors crucially regulate tumourigenesis resistance, including physical barriers, tumour microenvironment (TME), heterogeneity, genetic epigenetic alterations, immune system, burden, growth kinetics undruggable targets. Moreover, transforming factor-beta (TGF-β), Notch, epidermal factor receptor (EGFR), integrin-extracellular matrix (ECM), nuclear kappa-light-chain-enhancer activated B cells (NF-κB), phosphoinositol-3-kinase/protein kinase B/mammalian target rapamycin (PI3K/Akt/mTOR), wingless-related integration site (Wnt/β-catenin), Janus kinase/signal transducers activators transcription (JAK/STAT) RAS/RAF/mitogen-activated protein (MAPK) signalling pathways some key players that have a pivotal role mechanisms. To guide future treatments improve results, deeper comprehension necessary. This review covers intrinsic gives comprehensive overview recent research on enable to bypass barriers put up by treatments, and, like “satellite navigation”, find alternative routes which carry their “journey” progression.
Язык: Английский
Процитировано
45
Advanced Science, Год журнала: 2024, Номер 11(15)
Опубликована: Фев. 11, 2024
Abstract Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria‐mediated cell death. However, the highly adaptive nature damage‐repair capabilities malignant tumors strongly limit efficacy treatments based on a single treatment mode. To address this challenge, self‐reinforced bimetallic Mito‐Jammer is developed by incorporating doxorubicin (DOX) calcium peroxide (CaO 2 ) into hyaluronic (HA) ‐modified metal‐organic frameworks (MOF). After cellular, dissociates CaO Cu 2+ tumor microenvironment. The exposed further yields hydrogen (H O Ca weakly acidic environment to strengthen ‐based Fenton‐like reaction. Furthermore, combination chemodynamic therapy overload exacerbates ROS storms mitochondrial damage, resulting downregulation intracellular adenosine triphosphate (ATP) levels blocking Cu‐ATPase sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic death suppresses metastasis simultaneously. study presents multivariate model for revolutionizing mitochondria relying continuous retention ions boost cuproptosis/immunotherapy cancer.
Язык: Английский
Процитировано
33
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Авг. 14, 2024
Abstract Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression certain RTKs, are critical creating environments conducive tumor development. Following discovery, extensive research has revealed how RTK dysregulation contributes oncogenesis, with many subtypes showing dependency on aberrant signaling for proliferation, survival progression. These findings paved the way targeted therapies that aim inhibit crucial biological pathways cancer. As result, RTKs emerged as primary targets anticancer therapeutic Over past two decades, this led synthesis validation numerous small molecule kinase inhibitors (TKIs), now effectively utilized treating various types. In manuscript we provide comprehensive understanding context We explored alterations specific receptors across different malignancies, special dedicated examination current inhibitors, highlighting potential therapies. By integrating latest evidence, seek elucidate pivotal biology efficacy inhibition promising treatment outcomes.
Язык: Английский
Процитировано
23
Discover Oncology, Год журнала: 2024, Номер 15(1)
Опубликована: Авг. 11, 2024
Novel therapeutic agents in clinical trials offer a paradigm shift the approach to battling this prevalent and destructive disease, area of cancer therapy is on precipice trans formative revolution. Despite importance tried-and-true treatments like surgery, radiation, chemotherapy, disease continues evolve adapt, making new, more potent methods necessary. The field currently witnessing emergence wide range innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, vaccines, utilizes host's immune system selectively target eradicate malignant cells while minimizing harm normal tissue. development targeted medicines kinase inhibitors monoclonal antibodies has allowed for less harmful approaches treating cancer. With help genomics molecular profiling, "precision medicine" customizes therapies each patient's unique genetic makeup maximize efficacy unwanted side effects. Epigenetic therapies, metabolic interventions, radio-pharmaceuticals, an increasing emphasis combination with synergistic effects further broaden landscape. Multiple-stage are essential determining safety these novel drugs, allowing patients gain access also furthering scientific understanding. future rife promise, as integration artificial intelligence big data potential revolutionize early detection prevention. Collaboration among researchers, healthcare providers, active involvement remain bedrock ongoing battle against In conclusion, dynamic evolving landscape provides hope improved treatment outcomes, emphasizing patient-centered, data-driven, ethically grounded we collectively strive towards cancer-free world.
Язык: Английский
Процитировано
22
Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)
Опубликована: Янв. 13, 2025
The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.
Язык: Английский
Процитировано
10
Nature Communications, Год журнала: 2023, Номер 14(1)
Опубликована: Июль 25, 2023
Abstract Activated by its single ligand, hepatocyte growth factor (HGF), the receptor tyrosine kinase MET is pivotal in promoting glioblastoma (GBM) stem cell self-renewal, invasiveness and tumorigenicity. Nevertheless, HGF/MET-targeted therapy has shown limited clinical benefits GBM patients, suggesting hidden mechanisms of signalling GBM. Here, we show that circular RNA (circMET) encodes a 404-amino-acid variant (MET404) facilitated N 6 -methyladenosine (m A) reader YTHDF2. Genetic ablation circMET inhibits MET404 expression mice attenuates signalling. Conversely, knock-in (KI) plus P53 knock-out (KO) mouse astrocytes initiates tumorigenesis shortens overall survival. directly interacts with β subunit forms constitutively activated whose activity does not require HGF stimulation. High predicts poor prognosis indicating relevance. Targeting through neutralizing antibody or genetic reduces tumorigenicity vitro vivo, combinatorial are obtained addition traditional inhibitor. Overall, identify promotes tumorigenicity, offering potential therapeutic strategy for especially those hyperactivation.
Язык: Английский
Процитировано
33
ACS Synthetic Biology, Год журнала: 2023, Номер 12(4), С. 1081 - 1093
Опубликована: Апрель 3, 2023
In recent years, targeted protein degradation (TPD) of plasma membrane proteins by hijacking the ubiquitin proteasome system (UPS) or lysosomal pathway has emerged as a novel therapeutic avenue in drug development to address and inhibit canonically difficult targets. While TPD strategies have been successful targeting cell surface receptors, these approaches are limited availability suitable binders generate heterobifunctional molecules. Here, we present nanobody (VHH)-based toolbox termed REULR (Receptor Elimination E3 Ubiquitin Ligase Recruitment). We generated human mouse cross-reactive nanobodies against five transmembrane PA-TM-RING-type ligases (RNF128, RNF130, RNF167, RNF43, ZNRF3), covering broad range selectivity tissue expression, with which characterized expression lines immune cells (PBMCs). demonstrate that molecules can enforce ligase interactions variety disease-relevant target receptors (EGFR, EPOR, PD-1) induced proximity, resulting effective clearance receptor at varying levels. addition, designed self-degrading molecules, "fratricide" REULRs RENF167, allow downregulation one several from consequently modulate signaling strength. represent VHH-based modular versatile "mix match" strategy for facile modulation proximity PA-TM-RING ligases.
Язык: Английский
Процитировано
26
Cell Death and Disease, Год журнала: 2023, Номер 14(11)
Опубликована: Ноя. 11, 2023
Abstract Cervical cancer (CC) is a gynecological neoplasm with the highest incidence rate, primarily attributed to persistent infection of high-risk Human papillomavirus (HPV). Despite extensive research, pathogenesis CC remains unclear. N6-methyladenosine (m6A) methylation, most prevalent form epigenetic modification in RNA, intricately linked cell proliferation, metastasis, metabolism, and therapeutic resistance within tumor microenvironment (TME) CC. The involvement writer, reader, eraser m6A impacts advancement tumors through regulation RNA stability, nuclear export, translation efficiency, degradation. Here, we discuss biogenesis m6A, atypical expressions regulators, mechanisms molecular interactions, their functions Furthermore, elucidate non-coding RNA. In context precision medicine, advancements genomics, proteomics, high-throughput sequencing technologies, summarize application clinical diagnosis treatment Additionally, new perspectives on detection methods, immune regulation, nano-drug development are presented, which lay foundation for further research provide ideas
Язык: Английский
Процитировано
22
Journal of Controlled Release, Год журнала: 2024, Номер 366, С. 231 - 260
Опубликована: Янв. 4, 2024
Язык: Английский
Процитировано
13