A novel UBE2T inhibitor suppresses Wnt/β-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitination

Oncogene, Journal Year: 2020, Volume and Issue: 40(5), P. 1027 - 1042

Published: Dec. 15, 2020

Abstract Dysregulation of the Wnt/β-catenin signaling pathway is critically involved in gastric cancer (GC) progression. However, current Wnt inhibitors being studied preclinical or clinical settings for other cancers such as colorectal and pancreatic are either too cytotoxic insufficiently efficacious GC. Thus, we screened new potent targets from β-catenin destruction complex associated with GC progression samples, found that scaffolding protein RACK1 deficiency plays a significant role progression, but not APC, AXIN, GSK3β. Then, identified its upstream regulator UBE2T which promotes via hyperactivating through ubiquitination degradation at lysine K172, K225, K257 residues independent an E3 ligase. Indeed, level negatively prognosis patients, suggesting promising target therapy. Furthermore, novel inhibitor, M435-1279, suggested M435-1279 acts inhibit hyperactivation blocking UBE2T-mediated RACK1, resulting suppression lower cytotoxicity meantime. Overall, increased levels promote inhibitor providing balance between growth inhibition well, offer opportunity specific patients aberrant signaling.

Language: Английский

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The multidimensional role of the Wnt/β‐catenin signaling pathway in human malignancies

Journal of Cellular Physiology, Journal Year: 2021, Volume and Issue: 237(1), P. 199 - 238

Published: Aug. 25, 2021

Abstract Several signaling pathways have been identified as important for developmental processes. One of such cascades is the Wnt/β‐catenin pathway, which can regulate various physiological processes embryonic development, tissue homeostasis, and regeneration; while its dysregulation implicated in several pathological conditions especially cancers. Interestingly, deregulation pathway has reported to be closely associated with initiation, progression, metastasis, maintenance cancer stem cells, drug resistance human malignancies. Moreover, genetic experimental models support inhibition answer key issues related development. The present review focuses on different regulators Wnt how distinct mutations, deletion, amplification these could possibly play an essential role development cancers colorectal, melanoma, breast, lung, leukemia. Additionally, we also provide insights diverse classes inhibitors are currently preclinical clinical trial against

Language: Английский

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Targeting the crosstalk between canonical Wnt/β-catenin and inflammatory signaling cascades: A novel strategy for cancer prevention and therapy

Pharmacology & Therapeutics, Journal Year: 2021, Volume and Issue: 227, P. 107876 - 107876

Published: April 27, 2021

Language: Английский

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Prostate Cancer: A Journey Through Its History and Recent Developments

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 194 - 194

Published: Jan. 9, 2025

Prostate cancer is one of the most common diseases among men worldwide and continues to pose a serious threat health. This review shows history new developments in management prostate cancer, with an emphasis on range therapeutic approaches, such as hormone therapy, radiation surgery, innovative targeted therapeutics. The evolution these treatments examined light clinical outcomes, patient quality life, emerging resistance mechanisms, recently shown vitamin D-based strategies. New that have potential increase survival rates reduce side effects are also discussed, including PARP inhibitors (PARPis), immunotherapy, tailored medication. Additionally, use biomarkers sophisticated imaging methods decision-making explored, focus how tools might improve care. absolute necessity for multidisciplinary approach improving treatment strategies becoming more apparent our understanding biology deepens. ensures patients receive customized medicines fit their unique profiles. Future avenues investigation will resolving issues dealing efficacy results, ultimately leading disease cure patients.

Language: Английский

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Taking a Full Snapshot of Cancer Biology: Deciphering the Tumor Microenvironment for Effective Cancer Therapy in the Oncology Clinic

OMICS A Journal of Integrative Biology, Journal Year: 2020, Volume and Issue: 24(4), P. 175 - 179

Published: March 16, 2020

A bottleneck that is hindering therapeutics innovation in cancers the current lack of integration what we have learned tumor biology as well microenvironment (TME). This because tumors are complex tissues composed cancer cells, stromal and extracellular matrix (ECM). Although genetic alterations might cause initial uncontrolled growth, resistance to apoptosis cells play additional key roles within TME thus influence initiation, progression, therapy resistance, metastasis. Therapies targeting usually insufficient when component causes resistance. For treatment take a full snapshot biology, anticancer drug design must, therefore, target both component. expert review critically examines components such cancer-associated fibroblasts ECM can be reprogrammed create tumor-suppressive environment, thereby aiding treatment. Better experimental models mimic spheroids, microfluidics, three dimensional (3D) bioprinted models, organoids will allow deeper investigations complexity lead translation basic effective treatments. Ultimately, innovative treatments and, by extension, improvement patients' outcomes emerge from combinatorial development strategies TME. Combinatorial form chemotherapy radiotherapy (targeting components) immunotherapy able regulate immune responses against cells. addresses previously neglected knowledge gap broadening focus so empower disruptive health care innovations oncology clinic.

Language: Английский

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Development of artificial intelligence technology in diagnosis, treatment, and prognosis of colorectal cancer

World Journal of Gastrointestinal Oncology, Journal Year: 2022, Volume and Issue: 14(1), P. 124 - 152

Published: Jan. 10, 2022

Artificial intelligence (AI) technology has made leaps and bounds since its invention. AI can be subdivided into many technologies such as machine learning deep learning. The application scope prospect of different are also totally different. Currently, play a pivotal role in the highly complex wide-ranging medical field, image recognition, biotechnology, auxiliary diagnosis, drug research development, nutrition. Colorectal cancer (CRC) is common gastrointestinal that high mortality, posing serious threat to human health. Many CRCs caused by malignant transformation colorectal polyps. Therefore, early diagnosis treatment crucial CRC prognosis. methods diagnosing divided imaging endoscopy, pathology diagnosis. Treatment endoscopic treatment, surgical treatment. weak era does not have communication capabilities. current mainly used for recognition analysis without in-depth with patients. This article reviews prognosis provides prospects broader CRC.

Language: Английский

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The critical role of the phytosterols in modulating tumor microenvironment via multiple signaling: A comprehensive molecular approach

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 37(4), P. 1606 - 1623

Published: Feb. 9, 2023

Abstract Cancer is the leading cause of mortality and morbidity worldwide, its cases are rapidly increasing every year. Several factors contribute to development tumorigenesis. including radiation, dietary lifestyle, smoking, environmental, genetic factors. The cell cycle regulated by a variety molecular signaling proteins. However, when proteins involved in regulation altered, cellular growth proliferation significantly affected. Natural products provide an important source new drug for ailments. cancer. Phytosterols (PSs) class natural compounds reported numerous pharmacological activities, Various PSs, such as ergosterol, stigmasterol, sitosterol, withaferin A, etc., have been their anti‐cancer activities against cancer modulating tumor microenvironment via pathways discussed within article. These associated with production pro‐inflammatory mediators, factors, chemokines, pro‐apoptotic anti‐apoptotic genes. mediators upstream very active tumors these signalings, thus PS exhibits promising activities. further high‐quality studies needed firmly establish clinical efficacy well safety phytosterols.

Language: Английский

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Applications of quantum computing in clinical care

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: April 23, 2025

Introduction This review examines quantum computing (QC) applications in clinical care, emphasizing advancements directly impacting patient outcomes. QC holds transformative potential medicine, particularly through enhancing diagnostic accuracy, optimizing treatment plans, and enabling real-time decision-making. Methods A systematic analysis of 35 studies published between 2015 2024 was conducted. The were evaluated for their contributions to diagnostic, therapeutic, decision-support improvements care enabled by technologies. Results revealed QC’s promise improving accuracy medical imaging, treatments oncology, QC-driven algorithms demonstrated enhance computational efficiency. These could enable earlier detection diseases such as Alzheimer’s, cancer, osteoarthritis, supporting more timely interventions better prognoses. Discussion Despite promising outcomes, current limitations—such hardware scalability, error mitigation, ethical considerations—hinder widespread adoption settings. Overcoming these challenges will require interdisciplinary collaboration technological innovation. underscores capacity deliver precise, personalized, efficient advocating its integration into healthcare workflows advance precision medicine improve

Language: Английский

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Targeting Wnt/β-Catenin Pathway by Flavonoids: Implication for Cancer Therapeutics

Nutrients, Journal Year: 2023, Volume and Issue: 15(9), P. 2088 - 2088

Published: April 26, 2023

The Wnt pathway has been recognized for its crucial role in human development and homeostasis, but dysregulation also linked to several disorders, including cancer. signaling is the metastasis of kinds Moreover, members have proven be effective biomarkers promising cancer therapeutic targets. Abnormal stimulation initiation advancement both clinical research vitro investigations. A reduction incidence rate an improvement survival may result from targeting Wnt/β-catenin pathway. As a result, blocking this focus research, candidates that can targeted are currently being developed. Flavonoids derived plants exhibit growth inhibitory, apoptotic, anti-angiogenic, anti-migratory effects against various malignancies. flavonoids influence different pathways, Wnt, exert their anticancer effects. In review, we comprehensively evaluate on by focusing pathway, provide evidence impact number molecular Overall, review will enhance our understanding these natural products as modulators.

Language: Английский

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Broadening Drug Design and Targets to Tumor Microenvironment? Cancer-Associated Fibroblast Marker Expression in Cancers and Relevance for Survival Outcomes

OMICS A Journal of Integrative Biology, Journal Year: 2020, Volume and Issue: 24(6), P. 340 - 351

Published: June 1, 2020

Solid tumors have complex biology and structure comprising cancer cells, stromal the extracellular matrix. While most therapeutics target recent data suggest that cell behavior response to treatment are markedly influenced by tumor microenvironment (TME). In particular, cancer-associated fibroblasts (CAFs) abundant play a significant contextual role in shaping initiation, progression, metastasis. CAFs therefore emerged as part of next-generation drug design discovery innovation strategy. We report here new findings on differential expression prognostic significance CAF markers several cancers. utilized two publicly available resources: The Cancer Genomic Atlas Gene Expression Profiling Interactive Analysis. examined markers, ACTA2, S100A4, platelet-derived growth factor receptor-beta [PDGFR-β], CD10, fibroblast activation protein-alpha (FAP-α), tissues versus adjacent normal tissues. found were differentially expressed various different such colon, breast, esophageal cancers melanoma. No marker is same pattern all cancers, however. Importantly, we patients with colon adenocarcinoma carcinoma expressing high FAP-α respectively, had significantly shorter overall survival, compared those low levels these (p < 0.05). call for continued research TME clinical evaluation PDGFR-β, relation prognosis solid large population samples. An effective roadmap 21st century ought be broadly framed, include molecular targets informed both variations.

Language: Английский

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