Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Nov. 28, 2023

The advent of iPSCs has brought about a significant transformation in stem cell research, opening up promising avenues for advancing cancer treatment. formation is multifaceted process influenced by genetic, epigenetic, and environmental factors. offer distinctive platform investigating the origin cancer, paving way novel approaches to treatment, drug testing, tailored medical interventions. This review article will provide an overview science behind iPSCs, current limitations challenges iPSC-based therapy, ethical social implications, comparative analysis with other types also discuss applications tumorigenesis, future tumorigenesis highlight successful case studies utilizing research. conclusion summarize advancements made research importance continued investment iPSC unlock full potential these cells.

Language: Английский

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The Future of Precision Oncology

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12613 - 12613

Published: Aug. 9, 2023

Our understanding of the molecular mechanisms underlying cancer development and evolution have evolved rapidly over recent years, variation from one patient to another is now widely recognized. Consequently, one-size-fits-all approaches treatment been superseded by precision medicines that target specific disease characteristics, promising maximum clinical efficacy, minimal safety concerns, reduced economic burden. While oncology has very successful in some tumors with a large number patients do not yet access for their disease. The success next-generation depends on discovery new actionable rapid, accurate, comprehensive diagnosis complex phenotypes within each patient, novel trial designs improved response rates, worldwide targeted anticancer therapies all patients. This review outlines current technological trends, highlights multidisciplinary efforts are underway ensure many more will be able benefit near future.

Language: Английский

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Precision Oncology, Signaling Pathways Reprogramming and Targeted Therapy: A Holistic Approach to Molecular Cancer Therapeutics

Published: Jan. 8, 2025

Cancer is a fatal genetic disease involving unregulated cell growth and proliferation with varying underlying complexities including immune evasion, treatment resistance recurrence, optimized required for proper cure. Molecular studies have revealed that tumors are extremely heterogeneous in nature, leading to the complexity of cancer development, which ultimately linked its machinery. It would require effective targeting dysregulated molecular mechanisms factors, regulatory proteins, adhesion molecules, molecules system mainly driven by alterations tumor suppressor genes oncogenes may vary among different types. Importantly, patients same type respond differently available treatments, indicating need patient-specific options. Thus, in-depth genomic patients’ needed fully understand determinants initiation progression targeted therapy. Precision oncology has evolved as form therapy focused on profiling identify involved manifestation tailored individualized disease. Accordingly, there been great developments formulation production anticancer agents recent years owing advances technologies enabling precise oncogenic pathways progression. This article aims briefly explain foundations frontiers precision context advancements tools techniques associated process assess scope importance realizing intended goals.

Language: Английский

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Comprehensive Analysis of Ferroptosis Regulators With Regard to PD-L1 and Immune Infiltration in Clear Cell Renal Cell Carcinoma

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: July 5, 2021

Clear cell renal carcinoma (ccRCC) is one of the tumor types with sensitivity to ferroptosis, and immunotherapy has emerged as a standard pillar for metastatic ccRCC treatment, while it remains largely obscure whether ferroptosis influences immune microenvironment in ccRCC. Based on available data The Cancer Genome Atlas, divergent expression profiles regulators were noted normal tissues, we also found that correlated PD-L1 expression. Two independent subtypes determined by consensus clustering analysis according level Cluster 1 showed lower histological stage grade, more favorable prognosis, higher compared cluster 2. CIBERSORT revealed 2 harbored infiltrated levels CD8+ T cell, Tregs, follicular helper monocyte, M1 macrophage, M2 macrophage. Gene set enrichment indicated ERBB signaling JAK_STAT pathways significantly enriched 1. We subsequently identified CARS potentially key infiltration-related regulator, whose high dismal prognosis was positively verified upregulation tissues lines via qRT-PCR method. Additionally, pan-cancer demonstrated closely related checkpoint-related genes (especially PD-L1) an unfavorable diverse cancer types. In summary, our study suggested crucial role infiltration ccRCC, novel prognostic biomarker potential target immunotherapy.

Language: Английский

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How can we deliver on the promise of precision medicine in oncology and beyond? A practical roadmap for action

Health Science Reports, Journal Year: 2023, Volume and Issue: 6(6)

Published: June 1, 2023

Precision medicine (PM) is a form of personalized that recognizes individuals with the same condition may have different underlying factors and uses molecular information to provide tailored treatments. This approach can improve treatment outcomes transform lives through favorable risk/benefit ratios, avoidance ineffective interventions, possible cost savings, as evidenced in field lung cancer other oncology/therapeutic settings, including cardiac disease, diabetes, rare diseases. However, potential benefits PM yet be fully realized.

Language: Английский

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An Update on Protein Kinases as Therapeutic Targets—Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17600 - 17600

Published: Dec. 18, 2023

Protein kinases are one of the most significant drug targets in human proteome, historically harnessed for treatment cancer, cardiovascular disease, and a growing number other conditions, including autoimmune inflammatory processes. Since approval first kinase inhibitors late 1990s early 2000s, field has grown exponentially, comprising 98 approved therapeutics to date, 37 which were between 2016 2021. While many these small-molecule protein that interact orthosterically with ATP binding pocket have been massively successful oncological indications, their poor selectively isozymes limited them due toxicities application disease spaces. Thus, recent attention turned use alternative allosteric mechanisms improved platforms such as modified peptides design modulators enhanced selectivity pharmacological properties. Herein we review role different C (PKC) isoforms cancer particular PKC-family inhibitors. We discuss translational examples carefully consider advantages limitations each compound (Part I). also advances modulators, leverage molecular docking model inhibitor-kinase interactions, propose action will aid next-generation II).

Language: Английский

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Challenges and solutions to system-wide use of precision oncology as the standard of care paradigm

Cambridge Prisms Precision Medicine, Journal Year: 2024, Volume and Issue: 2

Published: Jan. 1, 2024

The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus drug development on these specific targets. To ensure we continue build concerted momentum improve outcomes across all cancer types, financial, and operational barriers need be addressed. For example, complete integration certification 'molecular tumour board' into 'standard care' ensures a unified clinical decision pathway that both counteracts fragmentation is cornerstone evidence-based delivery inside outside research setting. Generally, integrated has been restricted (common) types either within major centres or small regional networks. Here, solutions real-world genomics, pathology, surgery, oncological treatments, data from source systems analysis whole-body imaging as digital can facilitate cost-effectiveness analysis, trial recruitment, outcome assessment. This urgent imperative for also extends early diagnosis adjuvant treatment interventions, individualised vaccines, immune cell therapies, synthetic lethal therapeutics screening prevention. Oncology care worldwide require proactive step-changes include inter-operative working solve patient centred challenges inclusive, quality, sustainable, fair cost-effective adoption efficient delivery. Here highlight workforce, technical, clinical, regulatory economic prevent implementation precision at scale, offer systematic roadmap standard based minimal essential tools. These support tools, quality control, flows an ethical legal framework, training certification, monitoring feedback. Bridging operational, gaps demands joint actions public industry stakeholders national global boundaries.

Language: Английский

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Prognosis and immune infiltration analysis of endoplasmic reticulum stress-related genes in bladder urothelial carcinoma

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 15, 2022

Background: Abnormal activation of endoplasmic reticulum (ER) stress sensors and their downstream signalling pathways is a key regulator tumour growth, metastasis the response to chemotherapy, targeted therapy immunotherapy. However, study ER on immune microenvironment bladder urothelial carcinoma (BLCA) still insufficient. Methods: Firstly, 23 genes were selected analyse expression differences prognostic value in BLCA based existing genome atlas data. According level stress-related BLCA, two independent clusters identified using consensus cluster analysis. Subsequently, correlation between these terms was analysed. Finally, we analysed gene HSP90B1 its corresponding mechanism that affects microenvironment. Results: Consensus clustering showed worse prognosis higher immunoassay site-related (HAVCR2, PDCD1, CTLA4, CD274, LAG3, TIGIT PDCD1LG2) 1 compared with 2. Additionally, both TIMER CIBERSORT algorithms infiltrating cells significantly than as high indicated poor closely related PD1. We also immune-infiltrating cell biomarkers, which positive results. verified an immunohistochemical assay tissue microarray 100 patients validating potential biomarker BLCA. Conclusion: Our work reveals play crucial role immunological milieu, therapeutic target for cancer

Language: Английский

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Predicting cell line-specific synergistic drug combinations through a relational graph convolutional network with attention mechanism

Briefings in Bioinformatics, Journal Year: 2022, Volume and Issue: 23(6)

Published: Aug. 24, 2022

Identifying synergistic drug combinations (SDCs) is a great challenge due to the combinatorial complexity and fact that SDC cell line specific. The existing computational methods either did not consider specificity of SDC, or perform well by building model for each independently. In this paper, we present novel encoder-decoder network named SDCNet predicting line-specific SDCs. learns common patterns across different lines as features in one combinations. This realized considering graphs relational graph, constructing graph convolutional (R-GCN) encoder learn fuse deep representations drugs lines. An attention mechanism devised integrate from layers R-GCN according their relative importance so representation learning further enhanced. are exploited through partial parameter sharing decoders, which only reconstruct known SDCs but also predict new ones line. Experiments on various datasets demonstrate superior state-of-the-art robust when generalized training ones. Finally, case study again confirms effectiveness our method reliable

Language: Английский

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Molecular glues: enhanced protein-protein interactions and cell proteome editing

Medicinal Chemistry Research, Journal Year: 2022, Volume and Issue: 31(7), P. 1068 - 1087

Published: May 12, 2022

Abstract The druggable genome is limited by structural features that can be targeted small molecules in disease-relevant proteins. While orthosteric and allosteric protein modulators have been well studied, they are to antagonistic/agonistic functions. This approach modulation leaves many proteins as undruggable targets. Recently, protein-protein interaction has emerged a promising therapeutic field for previously Molecular glues heterobifunctional degraders such PROTACs facilitate interactions bring the proteasome into proximity induce degradation. In this review, we discuss function rational design of molecular glues, degraders, hydrophobic tag degraders. We also review historic novel targets challenges opportunities new field.

Language: Английский

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