New insight towards development of paclitaxel and docetaxel resistance in cancer cells: EMT as a novel molecular mechanism and therapeutic possibilities

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 141, P. 111824 - 111824

Published: June 25, 2021

Epithelial-to-mesenchymal transition (EMT) mechanism is responsible for metastasis and migration of cancer cells to neighboring tissues. Morphologically, epithelial are transformed mesenchymal cells, at molecular level, E-cadherin undergoes down-regulation, while an increase occurs in N-cadherin vimentin levels. Increasing evidence demonstrates role EMT mediating drug resistance cells. On the other hand, paclitaxel (PTX) docetaxel (DTX) two chemotherapeutic agents belonging taxene family, capable inducing cell cycle arrest via preventing microtubule depolymerization. Aggressive behavior resulted from EMT-mediated can lead PTX DTX resistance. Upstream mediators such as ZEB1/2, TGF-β, microRNAs, so on involved regulating response DTX. Tumor-suppressing factors inhibit promote sensitivity Furthermore, three different strategies including using anti-tumor compounds, gene therapy delivery systems have been developed suppressing EMT, enhancing cytotoxicity against that mechanistically discussed current review.

Language: Английский

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NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

Journal of Cellular Physiology, Journal Year: 2022, Volume and Issue: 237(7), P. 2770 - 2795

Published: May 13, 2022

Metastasis of tumor cells is a complex challenge and significantly diminishes the overall survival prognosis cancer patients. The epithelial-to-mesenchymal transition (EMT) well-known mechanism responsible for invasiveness cells. A number molecular pathways can regulate EMT in nuclear factor-kappaB (NF-κB) one them. translocation NF-κB p65 induce transcription several genes involved induction. present review describes interaction their association progression. Due to oncogenic role signaling, its activation enhances metastasis via This has been confirmed various cancers including brain, breast, lung gastric cancers, among others. ZEB1/2, transforming growth factor-β, Slug as inducers undergo upregulation by promote After induction driven NF-κB, significant decrease occurs E-cadherin levels, while N-cadherin vimentin levels an increase. noncoding RNAs potentially also function upstream mediators modulate NF-κB/EMT axis cancers. Moreover, mediating drug resistance Thus, suppressing sensitivity chemotherapeutic agents.

Language: Английский

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The long and short non-coding RNAs modulating EZH2 signaling in cancer

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

Published: March 2, 2022

Non-coding RNAs (ncRNAs) are a large family of RNA molecules with no capability in encoding proteins. However, they participate developmental and biological processes their abnormal expression affects cancer progression. These can function as upstream mediators different signaling pathways enhancer zeste homolog 2 (EZH2) is among them. Briefly, EZH2 belongs to PRCs exert functional roles cells due its methyltransferase activity. gene via inducing H3K27me3. In the present review, our aim provide mechanistic discussion ncRNAs role regulating cancers. MiRNAs dually induce/inhibit affect downstream targets such Wnt, STAT3 EMT. Furthermore, miRNAs regulate therapy response affecting signaling. It noteworthy that reduce miRNA by binding promoter exerting Small-interfering (siRNA) short-hairpin (shRNA) synthetic, short capable reducing suppressing LncRNAs mainly targeting miRNAs. lncRNAs induce modulating expression. Circular (CircRNAs), like lncRNAs, areas discussed review focus on molecular leading clinical translation.

Language: Английский

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Hyaluronic acid-based nanoplatforms for Doxorubicin: A review of stimuli-responsive carriers, co-delivery and resistance suppression

Carbohydrate Polymers, Journal Year: 2021, Volume and Issue: 272, P. 118491 - 118491

Published: July 27, 2021

An important motivation for the use of nanomaterials and nanoarchitectures in cancer therapy emanates from widespread emergence drug resistance. Although doxorubicin (DOX) induces cell cycle arrest DNA damage by suppressing topoisomerase activity, resistance to DOX has severely restricted its anti-cancer potential. Hyaluronic acid (HA) been extensively utilized synthesizing nanoparticles as it interacts with CD44 expressed on surface cells. Cancer cells can take up HA-modified through receptor-mediated endocytosis. Various types nanostructures such carbon nanomaterials, lipid polymeric nanocarriers have modified HA enhance delivery acid-based advanced materials provide a platform co-delivery genes drugs along efficacy overcome chemoresistance. In present review, potential methods application are discussed.

Language: Английский

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Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis

Cancers, Journal Year: 2021, Volume and Issue: 13(8), P. 1882 - 1882

Published: April 14, 2021

In cancer cells, a vital cellular process during metastasis is the transformation of epithelial cells towards motile mesenchymal called to transition (EMT). The cytoskeleton an active network three intracellular filaments: actin cytoskeleton, microtubules, and intermediate filaments. These filaments play central role in structural design cell behavior are necessary for EMT. During EMT, undergo as manifested by elongation, migration, invasion, coordinated reorganization. extremely dynamic structure, controlled balance assembly disassembly Actin-binding proteins regulate polymerization depolymerization. Microtubule reorganization also plays important migration polarization. Intermediate rearranged, switching vimentin-rich network, this protein used marker cell. Hence, targeting EMT regulating activities their key components may be potential solution metastasis. This review summarizes research done on physiological functions its process, effect multidrug-resistant (MDR) cells—highlight some future perspectives therapy cytoskeleton.

Language: Английский

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STAT3-EMT axis in tumors: Modulation of cancer metastasis, stemness and therapy response

Pharmacological Research, Journal Year: 2022, Volume and Issue: 182, P. 106311 - 106311

Published: June 15, 2022

Language: Английский

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Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: March 22, 2022

Abstract Prostate cancer is a leading cause of death worldwide and new estimates revealed prostate as the in men 2021. Therefore, strategies are pertinent treatment this malignant disease. Macroautophagy/autophagy “self-degradation” mechanism capable facilitating turnover long-lived toxic macromolecules organelles. Recently, attention has been drawn towards role autophagy how its modulation provides effective therapy. In present review, we provide mechanistic discussion cancer. Autophagy can promote/inhibit proliferation survival cells. Besides, metastasis cells affected (via induction inhibition) by autophagy. affect response to therapy such chemotherapy radiotherapy, given close association between apoptosis. Increasing evidence demonstrated that upstream mediators AMPK, non-coding RNAs, KLF5, MTOR others regulate Anti-tumor compounds, for instance phytochemicals, dually inhibit or induce For improving therapy, nanotherapeutics chitosan nanoparticles have developed. With respect context-dependent cancer, genetic tools siRNA CRISPR-Cas9 be utilized targeting autophagic genes. Finally, these findings translated into preclinical clinical studies improve prognosis patients. Graphical abstract

Language: Английский

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EMT mechanism in breast cancer metastasis and drug resistance: Revisiting molecular interactions and biological functions

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 155, P. 113774 - 113774

Published: Oct. 3, 2022

One of the malignant tumors in women that has involved both developed and developing countries is breast cancer. Similar to other types tumors, cancer cells demonstrate high metastatic nature. Besides, tumor have ability drug resistance. EMT related mechanism metastasis focus current manuscript highlighting function malignancy Breast increase their migration by induction During EMT, N-cadherin vimentin levels increase, E-cadherin decrease mediate EMT-induced invasion. Different kinds anti-cancer agents such as tamoxifen, cisplatin paclitaxel mediates chemoresistance feature cells. Furthermore, correlates with radio-resistance tumor. Clinical aspect reversing preventing chemotherapy or radiotherapy failure patients improving survival time. The anti-tumor suppress can be used for decreasing invasion increasing chemosensitivity lncRNAs, miRNAs factors modulate progression are discussed here.

Language: Английский

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Biological impact and therapeutic perspective of targeting PI3K/Akt signaling in hepatocellular carcinoma: Promises and Challenges

Pharmacological Research, Journal Year: 2022, Volume and Issue: 187, P. 106553 - 106553

Published: Nov. 16, 2022

Cancer progression results from activation of various signaling networks. Among these, PI3K/Akt contributes to proliferation, invasion, and inhibition apoptosis. Hepatocellular carcinoma (HCC) is a primary liver cancer with high incidence rate, especially in regions prevalence viral hepatitis infection. Autoimmune disorders, diabetes mellitus, obesity, alcohol consumption, inflammation can also lead initiation development HCC. The treatment HCC depends on the identification oncogenic factors that tumor cells develop resistance therapy. present review article focuses role progression. Activation promotes glucose uptake, favors glycolysis increases cell proliferation. It inhibits both apoptosis autophagy while promoting survival. stimulates epithelial-to-mesenchymal transition (EMT) matrix-metalloproteinase (MMP) expression during metastasis. In addition increasing colony formation capacity facilitating spread cells, angiogenesis. Therefore, silencing prevents aggressive behavior. confer drug resistance, particularly sorafenib, decreases radio-sensitivity cells. Anti-cancer agents, like phytochemicals small molecules suppress by limiting Being upregulated tissues clinical samples, be used as biomarker predict patients' response

Language: Английский

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Long non-coding RNAs and exosomal lncRNAs: Potential functions in lung cancer progression, drug resistance and tumor microenvironment remodeling

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 150, P. 112963 - 112963

Published: April 22, 2022

Among the different kinds of tumors threatening human life, lung cancer is one that commonly observed in both males and females. The aggressive behavior interactions occurring tumor microenvironment enhances malignancy this tumor. cells have demonstrated capacity developing chemo- radio-resistance. LncRNAs are a category non-coding RNAs do not encode proteins, but their aberrant expression responsible for development, especially cancer. In present review, we focus on lncRNAs exosomal cancer, ability regulating proliferation metastasis. Cell cycle progression molecular mechanisms related to metastasis such as EMT MMPs regulated by lncRNAs. interact with miRNAs, STAT, Wnt, EZH2, PTEN PI3K/Akt signaling pathways affect cells. demonstrate tumor-suppressor tumor-promoting functions They can be considered biomarkers body fluids potential tools minimally invasive diagnosis. Furthermore, discuss regulation anti-cancer drugs genetic well role these factors therapy response

Language: Английский

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