Current Landscape of Therapeutic Resistance in Lung Cancer and Promising Strategies to Overcome Resistance

Cancers, Journal Year: 2022, Volume and Issue: 14(19), P. 4562 - 4562

Published: Sept. 20, 2022

Lung cancer is one of the leading causes cancer-related deaths worldwide with a 5-year survival rate less than 18%. Current treatment modalities include surgery, chemotherapy, radiation therapy, targeted and immunotherapy. Despite advances in therapeutic options, resistance to therapy remains major obstacle effectiveness long-term treatment, eventually insensitivity, poor progression-free survival, disease relapse. Resistance mechanisms stem from genetic mutations and/or epigenetic changes, unregulated drug efflux, tumor hypoxia, alterations microenvironment, several other cellular molecular alterations. A better understanding these crucial for targeting factors involved resistance, establishing novel antitumor targets, developing strategies resensitize cells towards treatment. In this review, we summarize diverse driving radiotherapy, immunotherapy, promising help overcome resistance.

Language: Английский

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Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update

Non-Coding RNA, Journal Year: 2023, Volume and Issue: 9(2), P. 27 - 27

Published: April 13, 2023

Since the discovery of first microRNAs (miRNAs, miRs), understanding miRNA biology has expanded substantially. miRNAs are involved and described as master regulators major hallmarks cancer, including cell differentiation, proliferation, survival, cycle, invasion, metastasis. Experimental data indicate that cancer phenotypes can be modified by targeting expression, because act tumor suppressors or oncogenes (oncomiRs), they have emerged attractive tools and, more importantly, a new class targets for drug development in therapeutics. With use mimics molecules (i.e., small-molecule inhibitors such anti-miRS), these therapeutics shown promise preclinical settings. Some miRNA-targeted been extended to clinical development, mimic miRNA-34 treating cancer. Here, we discuss insights into role other non-coding RNAs tumorigenesis resistance summarize some recent successful systemic delivery approaches developments anticancer development. Furthermore, provide comprehensive overview trials finally list based on miRNAs.

Language: Английский

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Overcoming Chemotherapy Resistance in Metastatic Cancer: A Comprehensive Review

Biomedicines, Journal Year: 2024, Volume and Issue: 12(1), P. 183 - 183

Published: Jan. 15, 2024

The management of metastatic cancer is complicated by chemotherapy resistance. This manuscript provides a comprehensive academic review strategies to overcome resistance in cancer. presents background information on cells, highlighting its clinical significance and the current challenges associated with using treat delves into molecular mechanisms underlying subsequent sections. It discusses genetic alterations, mutations, epigenetic modifications that contribute development Additionally, role altered drug metabolism efflux mechanisms, as well activation survival pathways evasion cell death, are explored detail. thoroughly examined, covering various approaches have shown promise. These include combination therapy approaches, targeted therapies, immunotherapeutic strategies, repurposing existing drugs. Each strategy discussed terms rationale potential effectiveness. Strategies for early detection monitoring resistance, rational design vis-a-vis personalized medicine predictive biomarkers guiding treatment decisions, importance lifestyle supportive therapies improving outcomes discussed. Lastly, outlines implications strategies. insights ongoing trials emerging address cells. also explores opportunities translating laboratory findings practice identifies future directions novel therapeutic avenues. detailed analysis emphasizes understanding range addressing this critical issue treating

Language: Английский

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The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 28, 2024

Cancer chemoresistance is a problematic dilemma that significantly restrains numerous cancer management protocols. It can promote recurrence, spreading of cancer, and finally, mortality. Accordingly, enhancing the responsiveness cells towards chemotherapies could be vital approach to overcoming chemoresistance. Tumour express high level sphingosine kinase-1 (SphK1), which acts as protooncogenic factor responsible for synthesis sphingosine-1 phosphate (S1P). S1P released through Human ATP-binding cassette (ABC) transporter interact with other phosphosphingolipids components in interstitial fluid tumor microenvironment (TME), provoking communication, progression, invasion, metastasis. Also, associated several impacts, including anti-apoptotic behavior, metastasis, mesenchymal transition (EMT), angiogenesis, chemotherapy resistance. Recent reports addressed levels carcinomas, ovarian, prostate, colorectal, breast, HCC. Therefore, targeting S1P/SphK signaling pathway an emerging therapeutic efficiently attenuate In this review, we comprehensively discussed functions, metabolism, transport, signaling. bioinformatic framework, pointed out alterations SphK1 gene expression within different cancers their impact on patient survival, demonstrated protein-protein network SphK1, elaborating its sparse roles. Furthermore, made emphasis machineries resistance tight link S1P. We evaluated all publicly available inhibitors inhibition activity using molecular docking how reduce production might chemoresistance, course treatment prognosis.

Language: Английский

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Emerging roles of exosomes in oral diseases progression

International Journal of Oral Science, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 15, 2024

Abstract Oral diseases, such as periodontitis, salivary gland and oral cancers, significantly challenge health conditions due to their detrimental effects on patient’s digestive functions, pronunciation, esthetic demands. Delayed diagnosis non-targeted treatment profoundly influence patients’ prognosis quality of life. The exploration innovative approaches for early detection precise represents a promising frontier in medicine. Exosomes, which are characterized nanometer-sized extracellular vesicles, secreted by virtually all types cells. As the research continues, complex roles these intracellular-derived vesicles biological processes have gradually unfolded. Exosomes attracted attention valuable diagnostic therapeutic tools ability transfer abundant cargos intricate involvement multiple cellular functions. In this review, we provide an overview recent applications exosomes within field focusing inflammation-related bone diseases squamous cell carcinomas. We characterize exosome alterations demonstrate potential biomarkers diagnosis, highlighting indicators diseases. also summarize targeted therapy proposed future directions use clinical treatment.

Language: Английский

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Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 680 - 680

Published: Feb. 6, 2024

In recent years, the emergence of cancer drug resistance has been one crucial tumor hallmarks that are supported by level genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression ABC transporters, stemness among several key contributing molecular response mechanisms. Topo-active drugs, e.g., doxorubicin topotecan, clinically active utilized extensively against a wide variety human tumors often result in development failure to therapy. Thus, there is an urgent need for incremental comprehensive understanding mechanisms specifically context topo-active drugs. This review delves into intricate mechanistic aspects these intracellular extracellular explores use potential combinatorial approaches utilizing various drugs inhibitors pathways involved resistance. We believe this will help guide basic scientists, pre-clinicians, clinicians, policymakers toward holistic interdisciplinary strategies transcend resistance, renewing optimism ongoing battle cancer.

Language: Английский

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Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer

Molecular Biomedicine, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 6, 2025

Cancer remains a leading cause of mortality globally and major health burden, with chemotherapy often serving as the primary therapeutic option for patients advanced-stage disease, partially compensating limitations non-curative treatments. However, emergence resistance significantly limits its efficacy, posing clinical challenge. Moreover, heterogeneity mechanisms across cancer types complicates development universally effective diagnostic approaches. Understanding molecular chemoresistance identifying strategies to overcome it are current research focal points. This review provides comprehensive analysis key underlying resistance, including drug efflux, enhanced DNA damage repair (DDR), apoptosis evasion, epigenetic modifications, altered intracellular metabolism, role stem cells (CSCs). We also examine specific causes in highlight various targets involved resistance. Finally, we discuss aiming at overcoming such combination therapies, targeted treatments, novel delivery systems, while proposing future directions this evolving field. By addressing these barriers, lays foundation more therapies aimed mitigating

Language: Английский

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Cancer chemoresistance and its mechanisms: Associated molecular factors and its regulatory role

Medical Oncology, Journal Year: 2023, Volume and Issue: 40(9)

Published: Aug. 7, 2023

Language: Английский

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Carbon Dots-Based Nanozyme for Drug-Resistant Lung Cancer Therapy by Encapsulated Doxorubicin/siRNA Cocktail

International Journal of Nanomedicine, Journal Year: 2023, Volume and Issue: Volume 18, P. 933 - 948

Published: Feb. 1, 2023

Nanomaterials exhibited intrinsic enzyme-like properties due to the unique compared with natural enzyme. Carbon dots (CDs) are an important kind of quantum-sized nanomaterials, which have enormous application potential in bio-imaging, drug carrier, and nanosystems. possess properties, such as glutathione (GSH) oxidase or peroxidase activities.A co-delivery nanosystem that could carry siRNA doxorubucin (DOX) simultaneously has been studied this work. The based on carbon was surface-modified poly-ethylenimine (PEI) loaded siMRP1 chemotherapeutics surface pH-triggered release. CD-PEI synthesized by one-step microwave assisted method; PEI raw materials passivator during reaction process makes CDs exhibit excellent optical property.The capable loading delivering DOX tumors releasing them synchronously cells acid-triggered manner. particles GSH oxidase-like catalytic property, oxidizing oxidized concomitant increase reactive oxygen species (ROS). We found silencing MRP1 system antagonized chemoresistance increasing accumulation significantly enhancing inhibitory effect cell viability induced CD-PEI-DOX. dramatically inhibited tumor growth xenograft model, counteracted function siRNA-mediated knockdown MRP1.Taken together, we uncover role a combination overcoming lung cancer suppressing oxidation GSH. Our findings imply its antagonizing enhance therapeutic efficiency doxorubicin clinical practices treatment.

Language: Английский

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Insight into Iron, Oxidative Stress and Ferroptosis: Therapy Targets for Approaching Anticancer Strategies

Cancers, Journal Year: 2024, Volume and Issue: 16(6), P. 1220 - 1220

Published: March 20, 2024

Based on the multifaceted molecular machinery that tightly controls iron cellular homeostasis, this review delves into its paradoxical, potentially dangerous role in biological systems, with a special focus double-edged sword correlations cancer. Indeed, though is vital micronutrient and required cofactor participating several essential cell functions, tendency to cause oxidative stress can be related both cancer risk activation of death pathways. In scenario, ferroptosis refers an iron-dependent form regulated (RCD) powered by overload lethal peroxides sharing distinctive oxidized phospholipid profiles. As unique pathway, morphologically mechanistically different from other types programmed involving executioner family proteins. The accumulation cytotoxic lipid encompasses antagonism between execution defense occurring when ferroptosis-promoting activities significantly exceed antioxidant defenses. most recent breakthroughs have aroused great consideration tumor biology, as targeting provide new tools for exploring therapeutic strategies suppression. Mutations death/survival pathway alterations, well metabolic regulations cells, including propensity generate ROS, are seen features render cells unprotected ferroptosis, thereby exposing vulnerabilities which deserve further attention regarded targetable cancers limited options.

Language: Английский

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