Signaling pathways in the regulation of cancer stem cells and associated targeted therapy

MedComm, Journal Year: 2022, Volume and Issue: 3(4)

Published: Oct. 5, 2022

Cancer stem cells (CSCs) are defined as a subpopulation of malignant tumor with selective capacities for initiation, self-renewal, metastasis, and unlimited growth into bulks, which believed major cause progressive phenotypes, including recurrence, treatment failure. A number signaling pathways involved in the maintenance cell properties survival CSCs, well-established intrinsic pathways, such Notch, Wnt, Hedgehog signaling, extrinsic vascular microenvironment tumor-associated immune cells. There is also intricate crosstalk between these signal cascades other oncogenic pathways. Thus, targeting pathway molecules that regulate CSCs provides new option therapy-resistant or -refractory tumors. These treatments include small molecule inhibitors, monoclonal antibodies target key well CSC-directed immunotherapies harness systems to CSCs. This review aims provide an overview regulating networks their interactions CSC development. We address update on development therapeutics, special focus those application approval under clinical evaluation.

Language: Английский

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Advances in siRNA delivery approaches in cancer therapy: challenges and opportunities

Molecular Biology Reports, Journal Year: 2023, Volume and Issue: 50(11), P. 9529 - 9543

Published: Sept. 23, 2023

Language: Английский

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Current Technologies and Future Perspectives in Immunotherapy towards a Clinical Oncology Approach

Biomedicines, Journal Year: 2024, Volume and Issue: 12(1), P. 217 - 217

Published: Jan. 18, 2024

Immunotherapy is now established as a potent therapeutic paradigm engendering antitumor immune response against wide range of malignancies and other diseases by modulating the system either through stimulation or suppression components such CD4+ T cells, CD8+ B monocytes, macrophages, dendritic natural killer cells. By targeting several checkpoint inhibitors blockers (e.g., PD-1, PD-L1, PD-L2, CTLA-4, LAG3, TIM-3) expressed on surface monoclonal antibodies polyclonal have been developed already translated clinically. In addition, cell-based, CAR cell therapies also shown to be promising effective immunotherapeutic approaches. particular, therapy has benefited from advancements in CRISPR-Cas9 genome editing technology, allowing generation modified cells with enhanced immunity. However, emerging SARS-CoV-2 infection could hijack patient’s releasing pro-inflammatory interleukins cytokines IL-1β, IL-2, IL-6, IL-10, IFN-γ TNF-α, respectively, which can further promote neutrophil extravasation vasodilation blood vessels. Despite significant development advanced technologies, after certain period treatment, cancer relapses due resistance immunotherapy. Resistance may primary (where tumor do not respond treatment), secondary acquired develop gradually ICIs therapy). this context, review aims address existing technologies mechanisms drugs, explain impact COVID-19 treatment. we will discuss what future implementation these strategies drug resistance. Finally, emphasize practical steps lay groundwork for enlightened policy intervention resource allocation care patients.

Language: Английский

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The role of lncRNA NEAT1 in human cancer chemoresistance

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 5, 2024

Abstract Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance an important reason for poor efficacy and prognosis, which has become urgent problem to be solved field chemotherapy. Therefore, it very deeply study analyze mechanism its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) been shown closely associated with cancer. NEAT1 induces cell chemotherapeutic drugs by regulating apoptosis, cycle, drug transport metabolism, DNA damage repair, EMT, autophagy, stem characteristics, metabolic reprogramming. This indicates that may target overcome expected a potential biomarker predict effect article summarizes expression characteristics different cancers, discusses role related molecular mechanisms, aiming clarify as new feasibility sensitizers, view providing therapeutic direction overcoming dilemma future.

Language: Английский

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Molecular Docking of Lactoferrin with Apoptosis-Related Proteins Insights into Its Anticancer Mechanism

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2023 - 2023

Published: Feb. 26, 2025

Human Lactoferrin (hLf), a multifunctional glycoprotein, has been analyzed through molecular docking to evaluate its role in apoptosis regulation and potential as an anticancer agent. The results highlight XIAP (X-linked Inhibitor of Apoptosis Protein) Caspase-3 the most reliable targets, where hLf disrupts XIAP's inhibition Caspase-9, potentially restoring apoptotic signaling; also stabilizes Caspase-3, enhancing activation intrinsic extrinsic pathways. Weaker interactions were observed with Fas, Bcl-2, Akt. hLf's Fas signaling is likely due expression upregulation rather than direct binding. In contrast, binding Bcl-2 may disrupt anti-apoptotic function, interaction Akt suggests interference pro-survival signaling. These findings suggest that promote by caspase modulating key regulators, supporting use cancer treatment. However, further experimental validation needed confirm these their therapeutic implications.

Language: Английский

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Integrin-αvβ3 as a Therapeutic Target in Glioblastoma: Back to the Future?

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(5), P. 1053 - 1053

Published: May 13, 2022

Glioblastoma (GBM), the most common primary malignant brain tumor, is associated with a dismal prognosis. Standard therapies including maximal surgical resection, radiotherapy, and temozolomide chemotherapy remain poorly efficient. Improving GBM treatment modalities is, therefore, paramount challenge for researchers clinicians. GBMs exhibit hallmark feature of aggressive invasion into surrounding tissue. Among cell surface receptors involved in this process, members integrin family are known to be key actors invasion. Upregulation integrins was reported both tumor stromal cells, making them suitable target innovative targeting patients, as their impairment disrupts proliferation invasive capacities. them, integrin-αvβ3 expression correlates high-grade GBM. Driven by plethora preclinical biological studies, antagonists αvβ3 rapidly became attractive therapeutic candidates impair tumorigenesis. In perspective, advent nuclear medicine currently one greatest components theranostic concept clinical research fields. review, we provided an overview emphasize agents developed. Advanced current future developments field finally discussed.

Language: Английский

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The Aryl Hydrocarbon Receptor: Impact on the Tumor Immune Microenvironment and Modulation as a Potential Therapy

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 472 - 472

Published: Jan. 23, 2024

The aryl hydrocarbon receptor (AhR) is a ubiquitous nuclear with broad range of functions, both in tumor cells and immune within the microenvironment (TME). Activation AhR has been shown to have carcinogenic effect variety organs, through induction cellular proliferation migration, promotion epithelial-to-mesenchymal transition, inhibition apoptosis, among other functions. However, impact on cell function more complicated, pro- anti-tumorigenic roles identified. Although targeting cancer significant promise pre-clinical studies, there limited efficacy phase III clinical trials date. With contrasting activation polarization, understanding necessary guide therapies AhR. This review article summarizes state knowledge TME, limitations current findings, potential for modulation as therapy.

Language: Английский

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Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Dec. 18, 2024

Cancer remains a significant global challenge, and despite the numerous strategies developed to advance cancer therapy, an effective cure for metastatic elusive. A major hurdle in treatment success is ability of cells, particularly stem cells (CSCs), resist therapy. These CSCs possess unique abilities, including self-renewal, differentiation, repair, which drive tumor progression chemotherapy resistance. The resilience linked certain signaling pathways. Tumors with pathway-dependent often develop genetic resistance, whereas those pathway-independent undergo epigenetic changes that affect gene regulation. can evade cytotoxic drugs, radiation, apoptosis by increasing drug efflux transporter activity activating survival mechanisms. Future research should prioritize identification new biomarkers molecules better understand use cutting-edge approaches, such as bioinformatics, genomics, proteomics, nanotechnology, offers potential solutions this challenge. Key include developing targeted therapies, employing nanocarriers precise delivery, focusing on CSC-targeted pathways Wnt, Notch, Hedgehog Additionally, investigating multitarget inhibitors, immunotherapy, nanodrug delivery systems critical overcoming resistance cells.

Language: Английский

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Understanding the molecular mechanisms that regulate pancreatic cancer stem cell formation, stemness and chemoresistance: A brief overview

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 88, P. 67 - 80

Published: Dec. 16, 2022

Language: Английский

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Patient-derived zebrafish xenografts of uveal melanoma reveal ferroptosis as a drug target

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: June 16, 2023

Uveal melanoma (UM) has a high risk to progress metastatic disease with median survival of 3.9 months after metastases detection, as UM responds poorly conventional and targeted chemotherapy is largely refractory immunotherapy. Here, we present patient-derived zebrafish xenograft model mimicking UM. Cells isolated from Xmm66 spheroids derived patient material were injected into 2 days-old larvae resulting in micro-metastases the liver caudal hematopoietic tissue. Metastasis formation could be reduced by navitoclax more efficiently combinations navitoclax/everolimus flavopiridol/quisinostat. We obtained spheroid cultures 14 10 primary tissues, which used for xenografts success rate 100%. Importantly, ferroptosis-related genes GPX4 SLC7A11 are negatively correlated patients (TCGA: n = 80; Leiden University Medical Centre cohort: 64), ferroptosis susceptibility loss BAP1, one key prognosticators UM, induction greatly metastasis model. Collectively, have established animal identified possible therapeutic strategy treatment patients.

Language: Английский

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