TGFβ biology in cancer progression and immunotherapy

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 18(1), P. 9 - 34

Published: July 24, 2020

Language: Английский

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RNA demethylase ALKBH5 in cancer: from mechanisms to therapeutic potential

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Jan. 21, 2022

RNA demethylase ALKBH5 takes part in the modulation of N

Language: Английский

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Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 11, 2023

Abstract Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed circumvent tumor plasticity, including epigenetic modifications, regulation transcription factors, activation suppression key signaling pathways, as well modification environment. Epithelial-to-mesenchymal transition, stem formation also serve roads towards Corresponding treatment strategies recently developed that either target plasticity-related employ combination treatments. In this review, we delineate plasticity its manipulation evasion from therapy. We discuss non-genetic drug-induced various types tumors provide insights into contribution acquired drug resistance. New therapeutic such inhibition reversal are presented. multitude clinical trials ongoing worldwide with intention improving outcomes. These advances direction for developing novel therapy regimens

Language: Английский

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Unveiling the mechanisms and challenges of cancer drug resistance

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 12, 2024

Abstract Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer strategies are evolving due to innate acquired capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells survive progress under unfavorable conditions. Although the mechanism of drug being widely studied generate new target-based drugs with better potency than existing ones. However, broader flexibility in resistance, advanced therapeutic options efficacy need be explored. Combination therapy an alternative a success rate though risk amplified side effects commonplace. Moreover, recent groundbreaking precision immune ways overcome has revolutionized anticancer greater extent only limitation individual-specific needs further attention. This review will focus on challenges opted withstand current therapies at molecular level also highlights emerging -like immunological, stem cell-based may prove have potential challenge problem resistance.

Language: Английский

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Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution

Cancer and Metastasis Reviews, Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 9, 2023

Abstract The biological complexity of cancer represents a tremendous clinical challenge, resulting in the frequent failure current treatment protocols. In rapidly evolving scenario growing tumor, anticancer treatments impose drastic perturbation not only to cells but also tumor microenvironment, killing portion and inducing massive stress response survivors. Consequently, can act as double-edged sword by temporary while laying ground for therapy resistance subsequent disease progression. Cancer cell dormancy (or quiescence) is central theme evolution, being tightly linked tumor’s ability survive cytotoxic challenges, metastasize, resist immune-mediated attack. Accordingly, quiescent (QCCs) have been detected virtually all stages development. recent years, an increasing number studies focused on characterization quiescent/therapy resistant cells, unveiling QCCs core transcriptional programs, metabolic plasticity, mechanisms immune escape. At same time, our partial understanding quiescence reflects difficulty identify stable biomarkers/therapeutic targets control settings. This review focuses discoveries interrelated fields dormancy, stemness, resistance, discussing experimental evidences frame nonlinear dynamics approach, exploring possibility that may represent peril potential therapeutic resource.

Language: Английский

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Signaling pathways governing breast cancer stem cells behavior

Stem Cell Research & Therapy, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 16, 2021

Abstract Breast cancer is the second common and leading cause of malignancy among females overall. stem cells (BCSCs) are a small population breast that play critical role in metastasis to other organs body. BCSCs have both self-renewal differentiation capacities, which thought contribute aggressiveness metastatic lesions. Therefore, targeting can be suitable approach for treatment cancer. Growing evidence has indicated Wnt, NFκB, Notch, BMP2, STAT3, hedgehog (Hh) signaling pathways govern epithelial-to-mesenchymal transition (EMT) activation, growth, tumorigenesis primary regions. miRNAs as central regulatory molecules also roles BCSC self-renewal, metastasis, drug resistance. Hence, these might novel therapeutic diagnosis therapy. This review discusses known mechanisms involved stimulation or prevention tumorigenesis.

Language: Английский

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Mesenchymal Stem Cell–Secreted Extracellular Vesicles Instruct Stepwise Dedifferentiation of Breast Cancer Cells into Dormancy at the Bone Marrow Perivascular Region

Cancer Research, Journal Year: 2021, Volume and Issue: 81(6), P. 1567 - 1582

Published: Jan. 26, 2021

Abstract In the bone marrow (BM), breast cancer cells (BCC) can survive in dormancy for decades as stem (CSC), resurging tertiary metastasis. The endosteal region where BCCs exist CSCs poses a challenge to target them, mostly due coexistence of endogenous hematopoietic cells. This study addresses early period when enter BM at perivascular begin transition into CSCs, which we propose final step dormancy. A two-step process comprises Wnt-β-catenin pathway mediating BCC dedifferentiation niche. At this site, responded two types mesenchymal cell (MSC)–released extracellular vesicles (EV) that may include exosomes. Early released EVs began cycling quiescence, DNA repair, and reorganization distinct subsets. After contact with cancer, content changed (primed) complete more homogeneous population CSC properties. progenitors (Oct4alo), are distant from hierarchical stratification, were sensitive MSC EVs. Despite function, Oct4alo expressed multipotent pathways similar CSCs. dedifferentiated colocalized MSCs (murine human BM) vivo. Overall, these findings elucidate mechanism provide evidence epigenome potential new therapy cancer. Significance: These describe how initial niche requires cell–derived exosomes, indicating therapeutic intervention.

Language: Английский

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Targeting dormant tumor cells to prevent cancer recurrence

FEBS Journal, Journal Year: 2020, Volume and Issue: 288(21), P. 6286 - 6303

Published: Nov. 15, 2020

Over the years, developments in oncology led to significantly improved clinical outcome for cancer patients. However, recurrence after initial treatment response still poses a major challenge, as it often involves more aggressive, metastatic disease. The presence of dormant cells is associated with recurrence, metastasis, and poor outcome, suggesting that these may play crucial role process disease relapse. Cancer cell dormancy typically presents growth arrest while retaining proliferative capacity can be induced or reversed by wide array cell‐intrinsic cell‐extrinsic factors. Conventional therapies preferentially target fast‐dividing cells, leaving largely insensitive treatments. In this review, we discuss highlight how novel therapy strategies based on cell‐cycle modulation, modifications existing drugs, enhanced drug‐delivery vehicles used specifically subpopulation tumor thereby have potential prevent recurrence.

Language: Английский

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Pentadecanoic Acid, an Odd-Chain Fatty Acid, Suppresses the Stemness of MCF-7/SC Human Breast Cancer Stem-Like Cells through JAK2/STAT3 Signaling

Nutrients, Journal Year: 2020, Volume and Issue: 12(6), P. 1663 - 1663

Published: June 3, 2020

Saturated fatty acids possess few health benefits compared to unsaturated acids. However, increasing experimental evidence demonstrates the nutritionally beneficial role of odd-chain saturated in human health. In this study, anti-cancer effects pentadecanoic acid were evaluated breast carcinoma MCF-7/stem-like cells (SC), a cell line with greater mobility, invasiveness, and cancer stem properties parental MCF-7 cells. Pentadecanoic exerted selective cytotoxic MCF-7/SC Moreover, reduced stemness suppressed migratory invasive ability as evidenced by results flow cytometry, mammosphere formation assay, an aldehyde dehydrogenase activity Western blot experiments conducted analyze expression markers—CD44, β-catenin, MDR1, MRP1—and epithelial–mesenchymal transition (EMT) markers—snail, slug, MMP9, MMP2. addition, interleukin-6 (IL-6)-induced JAK2/STAT3 signaling, induced cycle arrest at sub-G1 phase, promoted caspase-dependent apoptosis MCF-7/SC. These findings indicate that can serve novel signaling inhibitor suggest acid-rich food intake during treatments.

Language: Английский

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Small in Size, but Large in Action: microRNAs as Potential Modulators of PTEN in Breast and Lung Cancers

Biomolecules, Journal Year: 2021, Volume and Issue: 11(2), P. 304 - 304

Published: Feb. 18, 2021

MicroRNAs (miRNAs) are well-known regulators of biological mechanisms with a small size 19-24 nucleotides and single-stranded structure. miRNA dysregulation occurs in cancer progression. miRNAs can function as tumor-suppressing or tumor-promoting factors via regulating molecular pathways. Breast lung cancers two malignant thoracic tumors which the abnormal expression plays significant role their development. Phosphatase tensin homolog (PTEN) is tumor-suppressor factor that capable suppressing growth, viability, metastasis cells downregulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling. PTEN downregulation breast to promote PI3K/Akt expression, leading uncontrolled proliferation, metastasis, resistance chemotherapy radiotherapy. upstream mediators dually induce/inhibit signaling affecting behavior cells. Furthermore, long non-coding RNAs circular regulate miRNA/PTEN axis It seems anti-tumor compounds such baicalein, propofol, curcumin induce upregulation by These topics discussed current review focus on

Language: Английский

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