Targeting cancer stem cell pathways for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Feb. 7, 2020

Abstract Since cancer stem cells (CSCs) were first identified in leukemia 1994, they have been considered promising therapeutic targets for therapy. These self-renewal capacity and differentiation potential contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, OCT4, Sox2, Nanog, KLF4, MYC. In addition, many intracellular signaling pathways, Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers activators transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target rapamycin), TGF (transforming growth factor)/SMAD, PPAR (peroxisome proliferator-activated receptor), well extracellular vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, mesenchymal cells, matrix, exosomes, shown be very important regulators CSCs. Molecules, vaccines, antibodies, CAR-T (chimeric antigen receptor T cell) developed specifically CSCs, some these factors already undergoing clinical trials. This review summarizes the characterization identification depicts major pathways that regulate CSC development, discusses targeted therapy

Language: Английский

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PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(9)

Published: Sept. 24, 2020

Abstract Multidrug resistance (MDR) is the dominant challenge in failure of chemotherapy cancers. Phosphatidylinositol 3-kinase (PI3K) a lipid kinase that spreads intracellular signal cascades and regulates variety cellular processes. PI3Ks are considered significant causes chemoresistance cancer therapy. Protein B (AKT) also downstream effecter PI3K signaling, it modulates several pathways, including inhibition apoptosis, stimulation cell growth, modulation metabolism. This review highlights aberrant activation PI3K/AKT as key link MDR. We summarize regulation numerous major targets correlated with pathway, which further related to MDR, expression apoptosis-related protein, ABC transport glycogen synthase kinase-3 beta (GSK-3β), synergism nuclear factor kappa (NF-κB) mammalian target rapamycin (mTOR), glycolysis.

Language: Английский

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Triple-Negative Breast Cancer: Current Understanding and Future Therapeutic Breakthrough Targeting Cancer Stemness

Cancers, Journal Year: 2019, Volume and Issue: 11(9), P. 1334 - 1334

Published: Sept. 9, 2019

Triple-negative breast cancer (TNBC) is that tested as negative for estrogen receptors (ER), progesterone (PR), and excess human epidermal growth factor receptor 2 (HER2) protein which accounts 15%–20% of all cases. TNBC considered to be a poorer prognosis than other types cancer, mainly because it involves more aggressive phenotypes are similar stem cell–like cells (cancer cell, CSC). Thus, targeted treatment remains major challenge in clinical practice. This review article surveys the latest evidence concerning role genomic alteration current responses, trials potential targeting sites, CSC drug resistance, strategies CSCs TNBC. Furthermore, insulin-like 1 (IGF-1R) nicotinic acetylcholine (nAChR) stemness expression, chemoresistance, metastasis their relevance treatments also discussed highlighted.

Language: Английский

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Exosomes and breast cancer drug resistance

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(11)

Published: Nov. 17, 2020

Abstract Drug resistance is a daunting challenge in the treatment of breast cancer (BC). Exosomes, as intercellular communicative vectors tumor microenvironment, play an important role BC progression. With in-depth understanding heterogeneity, emerging exosomes drug has attracted extensive attention. The functional proteins or non-coding RNAs contained secreted from and stromal cells mediate by regulating efflux metabolism, pro-survival signaling, epithelial–mesenchymal transition, stem-like property, microenvironmental remodeling. In this review, we summarize underlying associations between discuss unique biogenesis exosomes, change exosome cargo, pattern release response to treatment. Moreover, propose candidate biomarker predicting monitoring therapeutic potential target carrier reverse BC.

Language: Английский

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The role of polyphenols in overcoming cancer drug resistance: a comprehensive review

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: Jan. 3, 2022

Abstract Chemotherapeutic drugs are used to treat advanced stages of cancer or following surgery. However, cancers often develop resistance against drugs, leading failure treatment and recurrence the disease. Polyphenols a family organic compounds with more than 10,000 members which have three-membered flavan ring system in common. These natural known for their beneficial properties, such as free radical scavenging, decreasing oxidative stress, modulating inflammation. Herein, we discuss role polyphenols (mainly curcumin, resveratrol, epigallocatechin gallate [EGCG]) different aspects drug resistance. Increasing uptake by tumor cells, metabolism enzymes (e.g. cytochromes glutathione-S-transferases), reducing efflux some mechanisms increase sensitivity cells chemotherapeutic agents. also affect other targets overcoming chemoresistance including cell death (i.e. autophagy apoptosis), EMT, ROS, DNA repair processes, stem epigenetics miRNAs).

Language: Английский

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Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management

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

Published: July 18, 2022

Drug resistance represents a major obstacle in cancer management, and the mechanisms underlying stress adaptation of cells response to therapy-induced hostile environment are largely unknown. As central organelle for cellular energy supply, mitochondria can rapidly undergo dynamic changes integrate signaling pathways provide bioenergetic biosynthetic flexibility cells, which contributes multiple aspects tumor characteristics, including drug resistance. Therefore, targeting therapy overcoming has attracted increasing attention various types cancer. Multiple mitochondrial processes, dynamics, metabolism, apoptotic regulatory machinery, have been demonstrated be potential targets. However, recent insights into revealed complexity structure functions, elusive functions biology, inaccessibility mitochondria, posed challenges clinical application mitochondrial-based therapeutic strategies. discovery both novel mitochondria-targeting agents innovative approaches is urgently required. Here, we review most literature summarize molecular their intricate connection with In addition, an overview emerging strategies target effectively chemoresistance highlighted, emphasis on repositioning delivery approaches, may accelerate compounds therapy.

Language: Английский

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Tumor microenvironment enriches the stemness features: the architectural event of therapy resistance and metastasis

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Dec. 22, 2022

Cancer divergence has many facets other than being considered a genetic term. It is tremendous challenge to understand the metastasis and therapy response in cancer biology; however, it postulates opportunity explore possible mechanism surrounding tumor environment. Most deadly solid malignancies are distinctly characterized by their microenvironment (TME). TME consists of stromal components such as immune, inflammatory, endothelial, adipocytes, fibroblast cells. stem cells (CSCs) or stem-like small sub-set population within believed be responsible player self-renewal, metastasis, The correlation between CSCs remains an enigma understanding events resistance biology. Recent evidence suggests that dictates maintenance arbitrate progression metastasis. adipocyte, release growth factors, cytokines, chemokines, microRNAs, exosomes provide cues for gain CSC features. These intricate cross-talks fueled evolve into aggressive, invasive, migratory phenotypes development. In this review, we have abridged recent developments role factors how these influence transition further translate cancer.

Language: Английский

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Cancer Stem Cells—Key Players in Tumor Relapse

Cancers, Journal Year: 2021, Volume and Issue: 13(3), P. 376 - 376

Published: Jan. 20, 2021

Tumor relapse and treatment failure are unfortunately common events for cancer patients, thus often rendering an uncurable disease. Cancer stem cells (CSCs) a subset of endowed with tumor-initiating self-renewal capacity, as well high adaptive abilities. Altogether, these features contribute to CSC survival after one or multiple therapeutic approaches, leading tumor progression/relapse. Thus, elucidating the molecular mechanisms associated stemness-driven resistance is crucial development more effective drugs durable responses. This review will highlight exploited by CSCs overcome different strategies, from chemo- radiotherapies targeted therapies immunotherapies, shedding light on their plasticity insidious trait responsible adaptation/escape. Finally, novel CSC-specific approaches be described, providing evidence preclinical clinical applications.

Language: Английский

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Natural killer cells: a promising immunotherapy for cancer

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: May 23, 2022

Abstract As a promising alternative platform for cellular immunotherapy, natural killer cells (NK) have recently gained attention as an important type of innate immune regulatory cell. NK can rapidly kill multiple adjacent cancer through non-MHC-restrictive effects. Although tumors may develop resistance mechanisms to endogenous cell attack, in vitro activation, expansion, and genetic modification greatly enhance their anti-tumor activity give them the ability overcome drug resistance. Some these approaches been translated into clinical applications, trials infusion patients with hematological malignancies solid thus far yielded many encouraging results. CAR-T exhibited great success treating malignancies, but drawbacks include high manufacturing costs potentially fatal toxicity, such cytokine release syndrome. To issues, CAR-NK were generated engineering demonstrated significant responses lower adverse effects compared therapy. In this review, we summarize recent advances focusing on biology function, types therapy, future perspectives

Language: Английский

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Cancer stem cells: advances in knowledge and implications for cancer therapy

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

Published: July 5, 2024

Abstract Cancer stem cells (CSCs), a small subset of in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, maintain tumor heterogeneity. continues be significant global disease burden. In the past, surgery, radiotherapy, chemotherapy were main cancer treatments. The technology treatments develop advance, emergence targeted therapy, immunotherapy provides more options for patients certain extent. However, limitations efficacy treatment resistance still inevitable. Our review begins with brief introduction historical discoveries, original hypotheses, pathways regulate CSCs, such as WNT/β-Catenin, hedgehog, Notch, NF-κB, JAK/STAT, TGF-β, PI3K/AKT, PPAR pathway, their crosstalk. We focus on role CSCs various therapeutic outcomes resistance, including how affect content alteration related molecules, CSCs-mediated clinical value targeting refractory, progressed or advanced tumors. summary, efficacy, method is difficult determine. Clarifying regulatory mechanisms biomarkers currently mainstream idea.

Language: Английский

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