ALDH and cancer stem cells: Pathways, challenges, and future directions in targeted therapy

Life Sciences, Journal Year: 2024, Volume and Issue: 356, P. 123033 - 123033

Published: Aug. 31, 2024

Language: Английский

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Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets

MedComm, Journal Year: 2023, Volume and Issue: 4(1)

Published: Jan. 16, 2023

The family of aldehyde dehydrogenases (ALDHs) contains 19 isozymes and is involved in the oxidation endogenous exogenous aldehydes to carboxylic acids, which contributes cellular tissue homeostasis. ALDHs play essential parts detoxification, biosynthesis, antioxidants, are important value for cell proliferation, differentiation, survival normal body tissues. However, frequently dysregulated associated with various diseases like Alzheimer's disease, Parkinson's especially solid tumors. Notably, involvement tumor progression responsible maintenance stem-cell-like phenotype, triggering rapid aggressive clinical progressions. have captured increasing attention as biomarkers disease diagnosis prognosis. Nevertheless, these require further longitudinal studies large populations broad application. This review summarizes our current knowledge regarding potential tumors several non-tumor diseases, well recent advances understanding functions underlying molecular mechanisms development. Finally, we discuss therapeutic therapy an emphasis on their implications.

Language: Английский

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ALDH1A1 in breast cancer: A prospective target to overcome therapy resistance (Review)

Oncology Letters, Journal Year: 2025, Volume and Issue: 29(5), P. 1 - 17

Published: March 4, 2025

The expression of cytosolic aldehyde dehydrogenases (ALDHs), which mediate the last step in pathway synthesis all‑trans retinoic acid, is dysregulated various types human cancer, and has been associated with development cancer stem cells (CSCs) solid tumors hematological malignancies. CSCs are considered a minor fraction capacity to initiate neoplastic tumors. ALDH1A1 serves crucial role emergence CSC phenotype, induces malignant behavior promotes treatment resistance. Notably, ALDH1A1‑induced therapy resistance not exclusive just one group drugs, but affects diverse drugs that use different mechanisms kill cells. This diversity drug resistance‑inducing effects stemness‑supporting functions ALDH1A1. inhibition activity using chemicals or depletion via genetic approaches, such as small interfering RNA, can overcome pathways In context breast it critical only expected manifest stem‑like features, include increased From angle disease prognosis, extent association remains be determined through application cutting‑edge methods detect tracked biomarkers within

Language: Английский

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Identification of approved drugs with ALDH1A1 inhibitory potential aimed at enhancing chemotherapy sensitivity in cancer cells: an in-silico drug repurposing approach

Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 15

Published: Jan. 8, 2024

The aldehyde dehydrogenase 1A1 (ALDH1A1) also known as retinal dehydrogenase, is an enzyme normally involved in the cellular metabolism, development and detoxification processes healthy cells. However, it's considered a cancer stem cell marker its high levels of expression several cancers, including breast, lung, ovarian, colon have been associated with poor prognosis resistance to chemotherapy. Given crucial role chemotherapy by chemotherapeutic drugs, ALDH1A1 has attracted significant research interest potential therapeutic target for cancer. Though few synthetic inhibitors synthesized their efficacy proved in-vitro in-vivo studies, none them passed clinical trials so far. In this scenario, we performed in-silico study verify whether any already approved drugs used various purposes ability inhibit catalytic activity ALDH1A1, that they can be repurposed therapy. Keeping mind feasibility repurposing larger population selected from five widely drug categories such antibiotic, antiviral, antifungal, anti diabetic antihypertensive screening. Computational techniques like molecular docking, dynamics simulations MM-PBSA binding energy calculation screen drugs. Based on logical analysis results, propose three – telmisartan, irbesartan maraviroc thus increase sensitivity

Language: Английский

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Chromothripsis-Mediated Small Cell Lung Carcinoma

Cancer Discovery, Journal Year: 2024, Volume and Issue: 15(1), P. 83 - 104

Published: Aug. 26, 2024

Abstract Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that typically associated with tobacco exposure and inactivation of RB1 TP53 genes. Here, we performed detailed clinicopathologic, genomic, transcriptomic profiling an atypical subset SCLC lacked co-inactivation arose in never/light smokers. We found most cases were chromothripsis—massive, localized chromosome shattering—recurrently involving 11 or 12 resulting extrachromosomal amplification CCND1 co-amplification CCND2/CDK4/MDM2, respectively. Uniquely, these clinically tumors exhibited genomic pathologic links to pulmonary carcinoids, suggesting previously uncharacterized mode pathogenesis via transformation from lower-grade neuroendocrine their progenitors. Conversely, never-smokers harboring inactivated hallmarks adenocarcinoma-to-SCLC derivation, supporting two distinct pathways plasticity-mediated never-smokers. Significance: provide the first description unique lacking RB1/TP53 alterations identify extensive chromothripsis pathogenetic carcinoids as its hallmark features. This work defines novel entity among cancers, highlighting exceptional histogenesis, clinicopathologic characteristics, therapeutic vulnerabilities. See related commentary by Nadeem Drapkin, p. 8

Language: Английский

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Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer

Cancers, Journal Year: 2023, Volume and Issue: 15(17), P. 4419 - 4419

Published: Sept. 4, 2023

The superfamily of human aldehyde dehydrogenases (hALDHs) consists 19 isoenzymes which are critical for several physiological and biosynthetic processes play a major role in the organism’s detoxification via NAD(P) dependent oxidation numerous endogenous exogenous substrates to their corresponding carboxylic acids. Over last decades, ALDHs have been subject studies as it was revealed that differential expression patterns various cancer types associated either with carcinogenesis or promotion cell survival. Here, we attempt provide thorough review hALDHs’ diverse functions 3D structures particular emphasis on pathology resistance chemotherapy. We especially interested findings regarding association structural features changes effects enzymes’ functionalities. Moreover, an updated outline hALDHs inhibitors utilized experimental clinical settings therapy. Overall, this aims better understanding impact therapy from perspective.

Language: Английский

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Current strategies for early epithelial ovarian cancer detection using miRNA as a potential tool

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: April 16, 2024

Ovarian cancer is one of the most aggressive and significant malignant tumor forms in female reproductive system. It leading cause death among gynecological cancers owing to its metastasis. Since preliminary disease symptoms are lacking, it imperative develop early diagnostic biomarkers aid treatment optimization personalization. In this vein, microRNAs, which short sequence non-coding molecules, displayed great potential as highly specific sensitive biomarker. miRNAs have been extensively advocated proven serve an instrumental part clinical management cancer, especially ovarian by promoting cell progression, invasion, delayed apoptosis, epithelial-mesenchymal transition, metastasis cells, chemosensitivity resistance therapy. Here, we cover our present comprehension up-to-date microRNA-based approaches detect well current strategies, role microRNAs oncogenes or suppressor genes, their significance prognosis,

Language: Английский

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Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11185 - 11185

Published: Oct. 17, 2024

Cancer stem cells (CSCs), or tumor-initiating (TICs), are small subpopulations (0.0001-0.1%) of cancer that crucial for relapse and therapy resistance. The elimination each CSC is essential achieving long-term remission. Metabolic reprogramming, particularly lipids, has a significant impact on drug efficacy by influencing diffusion, altering membrane permeability, modifying mitochondrial function, adjusting the lipid composition within CSCs. These changes contribute to development chemoresistance in various cancers. intricate relationship between metabolism resistance CSCs an emerging area research, as different species play roles multiple stages autophagy. However, link autophagy context regulation remains unclear. Understanding interplay reprogramming could lead new approaches enhancing therapies reducing tumorigenicity these cells. In this review, we explore latest findings CSCs, including role key regulatory enzymes, inhibitors, contribution maintaining homeostasis. recent may provide critical insights identifying novel pharmacological targets effective anticancer treatment.

Language: Английский

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Radyoterapinin Metastatik Meme Kanseri Hücrelerindeki Mitokondri İlişkili Yolaklar Üzerine Etkisi

Ege Tıp Bilimleri Dergisi, Journal Year: 2025, Volume and Issue: 7(3), P. 86 - 95

Published: Jan. 3, 2025

AMAÇ: Radyoterapi, meme kanserinin tedavisinde önemli bir yöntemdir; ancak metastatik ve olmayan kanseri hücrelerinde mitokondri ilişkili yolaklar üzerindeki etkileri tam olarak anlaşılamamıştır. Bu çalışma, radyoterapinin fonksiyonu sinyal yolakları etkilerini, kanser hücrelerinin hayatta kalma, apoptoz ilerlemedeki rollerine odaklanarak incelemektedir. GEREÇ VE YÖNTEM: MCF-7 MDA-MB-231 hücre serileri kullanılan GEO veri tabanından verilerine ait GSE210306 erişim numarasına sahip ekspresyon verisi kullanılmıştır. Farklı şekilde ifade edilen genleri (DEG) bulmak için GEO2R ile analiz edildi. DEG’ler GO KEGG zenginleştirme analizleri gerçekleştirilmiştir. Cytoscape yazılımıyla protein-protein etkileşimi (PPI) ağı oluşturuldu radyo terapi sonrası etkilenen genler belirlendi. BULGULAR: sonucunda adjP-değeri

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Superhydrophilic Nanostructured Microparticles for Enhanced Phosphoprotein Enrichment from Alzheimer’s Disease Brain

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Alzheimer's disease (AD) is an incurable neurodegenerative disorder and closely related to abnormal phosphoproteoforms. The analysis of low-abundance phosphoproteoforms relies heavily on the enrichment phosphoproteins. However, existing phosphoprotein materials suffer from either low selectivity or coverage due unavoidable unspecific adsorption background proteins. Here, we propose a strategy nanostructure-enabled superhydrophilic surfaces synthesize Ti4+-functionalized nanostructured microparticles (SNMs-Ti4+) via emulsion interfacial polymerization process. In this process, hydrophilic hydrophobic monomers assemble into stable oil-in-water emulsion, producing with abundant phosphate nanoprotrusions surface. are subsequently functionalized Ti4+. SNMs-Ti4+ exhibit enormous Ti4+ modifications, which allow effectively adsorb phosphoproteins suppress Using these SNMs-Ti4+, identified 2256 HeLa cells, twice number those enriched commercial kits. From AD mouse brains, 2603 were successfully enriched, 10 times AD-related differentially regulated discovered than without enrichment. These show great prospects for biomarker detection, diagnosis, downstream biological process disclosure.

Language: Английский

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