Cancer Stemness Meets Immunity: From Mechanism to Therapy

Cell Reports, Journal Year: 2021, Volume and Issue: 34(1), P. 108597 - 108597

Published: Jan. 1, 2021

Cancer stem cells (CSCs) are self-renewing that facilitate tumor initiation, promote metastasis, and enhance cancer therapy resistance. Transcriptomic analyses across many types have revealed a prominent association between stemness immune signatures, potentially implying biological interaction such hallmark features of cancer. Emerging experimental evidence has substantiated the influence CSCs on cells, including tumor-associated macrophages, myeloid-derived suppressor T in microenvironment and, reciprocally, importance sustaining CSC its survival niche. This review covers cellular molecular mechanisms underlying symbiotic interactions how heterotypic signaling maintains tumor-promoting ecosystem informs therapeutic strategies intercepting this co-dependency.

Language: Английский

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CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer

Cells, Journal Year: 2020, Volume and Issue: 9(7), P. 1651 - 1651

Published: July 9, 2020

Radiotherapy (RT) is a modality of oncologic treatment that can be used to treat approximately 50% all cancer patients either alone or in combination with other modalities such as surgery, chemotherapy, immunotherapy, and therapeutic targeting. Despite the technological advances RT, which allow more precise delivery radiation while progressively minimizing impact on normal tissues, issues like radioresistance tumor recurrence remain important challenges. Tumor heterogeneity responsible for variation response different subpopulations. A main factor related presence stem cells (CSC) inside tumors, are metastases, relapses, RT failure, poor prognosis patients. The plasticity CSCs, process highly dependent epithelial–mesenchymal transition (EMT) associated cell dedifferentiation, complicates identification eradication CSCs it might involved disease relapse progression after irradiation. microenvironment interactions their niches also play an role RT. This review provides deep insight into characteristics mechanisms both primary metastasis radiation, radiobiological principles CSC Finally, we summarize major clinical trials development CSC-based therapies combined overcome radioresistance. better understanding potential targets radiosensitization will provide safer efficient strategies, turn improve live expectancy curability

Language: Английский

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Glutathione S-Transferases in Cancer

Antioxidants, Journal Year: 2021, Volume and Issue: 10(5), P. 701 - 701

Published: April 29, 2021

In humans, the glutathione S-transferases (GST) protein family is composed of seven members that present remarkable structural similarity and some degree overlapping functionalities. GST proteins are crucial antioxidant enzymes regulate stress-induced signaling pathways. Interestingly, overactive a frequent feature many human cancers. Recent evidence has revealed biology most complex multifaceted these actively participate in tumorigenic processes such as cell survival, proliferation, drug resistance. Structural pharmacological studies have identified various inhibitors, molecules progressed to clinical trials for treatment cancer other diseases. this review, we discuss recent findings their roles development, contribution chemoresistance, development inhibitors treatment.

Language: Английский

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Nano-Based Approved Pharmaceuticals for Cancer Treatment: Present and Future Challenges

Biomolecules, Journal Year: 2022, Volume and Issue: 12(6), P. 784 - 784

Published: June 4, 2022

Cancer is one of the main causes death worldwide. To date, and despite advances in conventional treatment options, therapy cancer still far from optimal due to non-specific systemic biodistribution antitumor agents. The inadequate drug concentrations at tumor site led an increased incidence multiple resistance appearance many severe undesirable side effects. Nanotechnology, through development nanoscale-based pharmaceuticals, has emerged provide new innovative drugs overcome these limitations. In this review, we overview approved nanomedicine for rationale behind their designs applications. We also highlight approaches that are currently under investigation perspectives challenges nanopharmaceuticals, focusing on microenvironment disseminate cells as most attractive effective strategies treatments.

Language: Английский

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Molecular and cellular paradigms of multidrug resistance in cancer

Cancer Reports, Journal Year: 2020, Volume and Issue: 5(12)

Published: Oct. 13, 2020

The acquisition of resistance to chemotherapy is a major hurdle in the successful application cancer therapy. Several anticancer approaches, including chemotherapies, radiotherapy, surgery and targeted therapies are being employed for treatment cancer. However, cells reprogram themselves multiple ways evade effect these therapies, over period time, drug becomes inactive due development multi-drug (MDR). MDR complex phenomenon where malignant become insensitive drugs attain ability survive even after several exposures drugs. In this review, we have discussed molecular cellular paradigms multidrug cancer.An Extensive research biology revealed that result perpetuated intracellular extracellular mechanisms such as efflux, inactivation, target alteration, oncogenic mutations, altered DNA damage repair mechanism, inhibition programmed cell death signaling, metabolic reprogramming, epithelial mesenchymal transition (EMT), inherent heterogeneity, epigenetic changes, redox imbalance, or any combination mechanisms. An inevitable cross-link between inflammation has been discussed. This review provided insight mechanism understand vulnerabilities develop resistance.MDR an outcome interplays intricate pathways responsible inactivation resistance. obstacle regimens anti-cancer improved understanding multi reprogramming can provide promising opportunity combat intensify therapy upcoming future.

Language: Английский

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Flavonoids in Cancer Metastasis

Cancers, Journal Year: 2020, Volume and Issue: 12(6), P. 1498 - 1498

Published: June 8, 2020

Metastasis represents a serious complication in the treatment of cancer. Flavonoids are plant secondary metabolites exerting various health beneficiary effects. The effects flavonoids against cancer associated not only with early stages process, but also progression and spread into distant sites. showed potent anti-cancer models vitro vivo, mediated via regulation key signaling pathways involved migration invasion cells metastatic progression, including regulators epithelial-mesenchymal transition or regulatory molecules such as MMPs, uPA/uPAR, TGF-β other contributors complex process spread. Moreover, modulated expression genes improved inflammatory status, part development metastasis. documented clear potential to improve effectiveness conventional chemotherapeutic agents. Most importantly, represent environmentally-friendly cost-effective substances; moreover, wide spectrum different demonstrated safety minimal side during long-termed administration. In addition, bioavailability can be by their conjugation metal ions structural modifications radiation. conclusion, flavonoids, targeting all phases carcinogenesis should implemented clinical research order strengthen use future targeted prevention therapy high-risk individuals patients aggressive disease potential.

Language: Английский

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Surmounting cancer drug resistance: New insights from the perspective of N6-methyladenosine RNA modification

Drug Resistance Updates, Journal Year: 2020, Volume and Issue: 53, P. 100720 - 100720

Published: Aug. 20, 2020

Language: Английский

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Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer

Pharmacological Research, Journal Year: 2021, Volume and Issue: 171, P. 105759 - 105759

Published: July 8, 2021

Language: Английский

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Epithelial-Mesenchymal Transition (EMT) as a Therapeutic Target

Cells Tissues Organs, Journal Year: 2021, Volume and Issue: 211(2), P. 157 - 182

Published: Jan. 5, 2021

Metastasis is the spread of cancer cells from primary tumour to distant sites and organs throughout body. It cause morbidity mortality, estimated account for 90% cancer-related deaths. During initial steps metastatic cascade, epithelial undergo an epithelial-mesenchymal transition (EMT), as a result become migratory invasive mesenchymal-like while acquiring stem cell properties therapy resistance. As EMT involved in such broad range processes associated with malignant transformation, it has increasingly interesting target development novel therapeutic strategies. Anti-EMT strategies could potentially not only prevent invasion dissemination cells, formation lesions, but also attenuate stemness increase effectiveness more classical chemotherapeutics. In this review, we give overview about pros cons therapies targeting discuss some already existing candidate drug targets high-throughput screening tools identify anti-EMT compounds.

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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