Drug repurposing for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 18, 2024

Abstract Cancer, a complex and multifactorial disease, presents significant challenge to global health. Despite advances in surgical, radiotherapeutic immunological approaches, which have improved cancer treatment outcomes, drug therapy continues serve as key therapeutic strategy. However, the clinical efficacy of is often constrained by resistance severe toxic side effects, thus there remains critical need develop novel therapeutics. One promising strategy that has received widespread attention recent years repurposing: identification new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages context since repurposed drugs are typically cost-effective, proven be safe, can significantly expedite development process due their already established safety profiles. In light this, present review offers comprehensive overview various methods employed repurposing, specifically focusing on treat cancer. We describe antitumor properties candidate drugs, discuss detail how they target both hallmarks tumor cells surrounding microenvironment. addition, we examine innovative integrating with nanotechnology enhance topical delivery. also emphasize role play when used part combination regimen. To conclude, outline challenges associated consider future prospects these transitioning into application.

Language: Английский

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Dissection of FOXO1-Induced LYPLAL1-DT Impeding Triple-Negative Breast Cancer Progression via Mediating hnRNPK/β-Catenin Complex

Research, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

Triple-negative breast cancer (TNBC) is considered as the most hazardous subtype of owing to its accelerated progression, enormous metastatic potential, and refractoriness standard treatments. Long noncoding RNAs (lncRNAs) are extremely intricate in tumorigenesis cancerous metastasis. Nonetheless, their roles initiation augmentation TNBC remain elusive. Here, silico analysis validation experiments were utilized analyze expression pattern clinically effective lncRNAs TNBC, among which a protective lncRNA LYPLAL1-DT was essentially curbed samples indicated favorable prognosis. Gain- loss-of-function assays elucidated that considerably attenuated proliferative properties along with epithelial-mesenchymal transition cells. Moreover, forkhead box O1 (FOXO1) validated modulate transcription LYPLAL1-DT. Mechanistically, impinged on malignancy mainly by restraining aberrant reactivation Wnt/β-catenin signaling pathway, explicitly destabilizing diminishing β-catenin protein interacting heterogeneous nuclear ribonucleoprotein K (hnRNPK) constricting formation hnRNPK/β-catenin complex. Conclusively, our present research revealed anti-oncogenic effects unraveling molecular mechanisms FOXO1/LYPLAL1-DT/hnRNPK/β-catenin axis, shed innovative light potential curative medicine TNBC.

Language: Английский

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PI3K/AKT signaling pathway as a critical regulator of epithelial-mesenchymal transition in colorectal tumor cells

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 14, 2023

Abstract Colorectal cancer (CRC) is one of the most frequent gastrointestinal malignancies that are considered as a global health challenge. Despite many progresses in therapeutic methods, there still high rate mortality among CRC patients associated with poor prognosis and distant metastasis. Therefore, investigating molecular mechanisms involved metastasis can improve prognosis. Epithelial-mesenchymal transition (EMT) process main metastasis, which be regulated by various signaling pathways. PI3K/AKT pathway has key role cell proliferation migration. In present review, we discussed through regulation EMT process. It been shown induce down epithelial markers, while up mesenchymal markers EMT-specific transcription factors promote This review an effective step toward introducing PI3K/AKT/EMT axis to predict well target patients.

Language: Английский

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Role of Epithelial to Mesenchymal Transition in Colorectal Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14815 - 14815

Published: Oct. 1, 2023

The epithelial–mesenchymal transition (EMT) is a cellular reprogramming process that occurs during embryonic development and adult tissue homeostasis. This involves epithelial cells acquiring mesenchymal phenotype. Through EMT, cancer acquire properties associated with more aggressive EMT its opposite, mesenchymal–epithelial (MET), have been described in tumors over the past ten years, including colorectal (CRC). When activated, expression of marker E-cadherin decreased vimentin raised. As result, temporarily take on phenotype, becoming motile promoting spread tumor cells. Epithelial–mesenchymal plasticity (EMP) has become hot issue CRC because strong inducers (such as transforming growth factor β, TGF-β) can initiate regulate metastasis, microenvironment, immune system resistance CRC. In this review, we into account significance EMT-MET impact cells’ prognosis analysis connection between stem (CCSCs) will help to further clarify current meager understandings EMT. Recent advances affecting important transcription factors CCSCs are highlighted. We come conclusion regulatory network for complicated, great deal crosstalk alternate paths. More thorough research required effectively connect clinical management biomarkers targeted treatments

Language: Английский

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Focal adhesion kinase: from biological functions to therapeutic strategies

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: Sept. 25, 2023

Focal adhesion kinase (FAK), a nonreceptor cytoplasmic tyrosine kinase, is vital participant in primary cellular functions, such as proliferation, survival, migration, and invasion. In addition, FAK regulates cancer stem cell activities contributes to the formation of tumor microenvironment (TME). Importantly, increased expression activity are strongly associated with unfavorable clinical outcomes metastatic characteristics numerous tumors. vitro vivo studies have demonstrated that modulating by application inhibitors alone or combination treatment regimens could be effective for therapy. Based on these findings, several agents targeting been exploited diverse preclinical models. This article briefly describes structure function FAK, well research progress therapies. We also discuss challenges future directions regarding anti-FAK

Language: Английский

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Hallmarks of cancer resistance

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109979 - 109979

Published: May 15, 2024

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized Warburg effect, and dynamic interplay between cells mitochondria. The role stem (CSCs) in treatment resistance regulatory influence non-coding RNAs, such as long RNAs (lncRNAs), microRNAs (miRNAs), circular (circRNAs), are studied. chapter emphasizes future directions, encompassing advancements immunotherapy, strategies to counter adaptive integration artificial intelligence for predictive modeling, identification biomarkers personalized treatment. comprehensive exploration these provides a foundation innovative therapeutic approaches, aiming navigate complex landscape enhance patient outcomes.

Language: Английский

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circNOX4 activates an inflammatory fibroblast niche to promote tumor growth and metastasis in NSCLC via FAP/IL-6 axis

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: March 8, 2024

Abstract Background Cancer-associated fibroblasts (CAFs) orchestrate a supportive niche that fuels cancer metastatic development in non-small cell lung (NSCLC). Due to the heterogeneity and plasticity of CAFs, manipulating activated phenotype is promising strategy for therapy. However, underlying mechanisms fibroblast activation switching drive metastasis remain elusive. Methods The clinical implications protein (FAP)-positive CAFs (FAP + CAFs) were evaluated based on tumor specimens from NSCLC patients bioinformatic analysis online databases. CAF-specific circular RNAs (circRNAs) screened by circRNA microarrays primary human matched normal (NFs). Survival analyses performed assess prognostic value circNOX4 samples. biological effects investigated gain- loss-of-function experiments vitro vivo. Fluorescence situ hybridization, luciferase reporter assays, RNA immunoprecipitation, miRNA rescue conducted elucidate activation. Cytokine antibody array, transwell coculture system, enzyme-linked immunosorbent assay (ELISA) investigate downstream effectors promote metastasis. Results FAP significantly enriched samples, their higher abundance was correlated with worse overall survival patients. A novel circRNA, (hsa_circ_0023988), evoked phenotypic transition NFs into promoted migration invasion Clinically, poor prognosis advanced Mechanistically, upregulated sponging miR-329-5p, which led Furthermore, circNOX4/miR-329-5p/FAP axis an inflammatory preferentially inducing interleukin-6 (IL-6) eventually promoting progression. Disruption intercellular circNOX4/IL-6 suppressed growth colonization Conclusions Our study reveals role circRNA-induced highlights targeting circNOX4/FAP/IL-6 intervention

Language: Английский

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Wnt/β-catenin signalling, epithelial-mesenchymal transition and crosslink signalling in colorectal cancer cells

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116685 - 116685

Published: May 5, 2024

Colorectal cancer (CRC), with its significant incidence and metastatic rates, profoundly affects human health. A common oncogenic event in CRC is the aberrant activation of Wnt/β-catenin signalling pathway, which drives both initiation progression disease. Persistent facilitates epithelial-mesenchymal transition (EMT), accelerates invasion metastasis. This review provides a summary recent molecular studies on role axis regulating EMT cells, triggers pathogenesis. We present comprehensive examination process transcriptional controllers, an emphasis crucial functions β-catenin, transcription factors (EMT-TFs). also evidences showing that hyperactive phenotypes via "Destruction complex" β-catenin mechanisms. Potential therapeutic challenges approache to suppress prevent cells metastasis by targeting are discussed. These include direct inhibitors novel targets Wnt finally highlight potential combinational treatment options based inhibition pathway.

Language: Английский

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Dynamics of resistance to immunotherapy and TKI in patients with advanced renal cell carcinoma

Cancer Treatment Reviews, Journal Year: 2025, Volume and Issue: 133, P. 102881 - 102881

Published: Jan. 6, 2025

Language: Английский

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Injecting hope: the potential of intratumoral immunotherapy for locally advanced and metastatic cancer

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Despite enormous progress, advanced cancers are still one of the most serious medical problems in current society. Although various agents and therapeutic strategies with anticancer activity known used, they often fail to achieve satisfactory long-term patient outcomes survival. Recently, immunotherapy has shown success patients by harnessing important interactions between immune system cancer. However, many these therapies lead frequent side effects when administered systemically, prompting treatment modifications or discontinuation or, severe cases, fatalities. New approaches like intratumoral immunotherapy, characterized reduced effects, cost, systemic toxicity, offer promising prospects for future applications clinical oncology. In context locally metastatic cancer, combining diverse immunotherapeutic other targeting multiple cancer hallmarks appears crucial. Such combination hold promise improving survival promoting a sustained response. This review aims provide overview approaches, specifically focusing on administration drugs cancers. It also explores integration modalities maximize Additionally, summarizes recent advances discusses novel outlining directions field.

Language: Английский

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