Purinergic Signalling, Journal Year: 2024, Volume and Issue: unknown
Published: Aug. 31, 2024
Language: Английский
Non-coding RNA Research, Journal Year: 2024, Volume and Issue: 9(2), P. 277 - 287
Published: Jan. 26, 2024
The intricate molecular landscape of cancer pathogenesis continues to captivate researchers worldwide, with Circular RNAs (circRNAs) emerging as pivotal players in the dynamic regulation biological functions. study investigates elusive link between circRNAs and Transforming Growth Factor-β (TGF-β) signalling pathway, exploring their collective influence on progression metastasis. Our comprehensive investigation begins by profiling circRNA expression patterns diverse types, revealing a repertoire intricately linked TGF-β pathway. Through integrated bioinformatics analyses functional experiments, we elucidate specific circRNA-mRNA interactions that modulate signalling, unveiling regulatory controls governing this crucial Furthermore, provide compelling evidence impact circRNA-mediated modulation key cellular processes, including epithelial-mesenchymal transition (EMT), migration, cell proliferation. In addition mechanistic roles, have shown promise diagnostic prognostic biomarkers, well potential targets for therapy. Their ability critical pathways, such axis, underscores significance biology clinical applications. interplay is dissected, uncovering novel circuits contribute complexity biology. This review unravels previously unexplored dimension carcinogenesis, emphasizing role shaping landscape.
Language: Английский
Citations
16
Cancers, Journal Year: 2022, Volume and Issue: 15(1), P. 62 - 62
Published: Dec. 22, 2022
Recent studies have shown that oxidative phosphorylation (OXPHOS) is a target for the effective attenuation of cancer drug resistance. OXPHOS inhibitors can improve treatment responses to anticancer therapy in certain cancers, such as melanomas, lymphomas, colon leukemias and pancreatic ductal adenocarcinoma (PDAC). However, effect on resistance complex associated with cell types tumor microenvironment (TME). Cancer cells universally promote activity through activation various signaling pathways, this required therapy. Resistant are prevalent among stem (CSCs), which main metabolic phenotype increased OXPHOS. CSCs depend survive targeting by drugs be selectively eradicated inhibitors. In contrast cells, mitochondrial significantly downregulated tumor-infiltrating T impairing antitumor immunity. review, we summarize novel research showing resistance, thereby explaining how process plays dual role progression. We highlight underlying mechanisms reprogramming it vital discovering new targets.
Language: Английский
Citations
56
Cancer Cell, Journal Year: 2024, Volume and Issue: 42(12), P. 2064 - 2081.e19
Published: Nov. 7, 2024
Language: Английский
Citations
12
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7030 - 7030
Published: April 10, 2023
The first discovery of cancer stem cells (CSCs) in leukaemia triggered active research on stemness neoplastic tissues. CSCs represent a subpopulation malignant cells, defined by unique properties: dedifferentiated state, self-renewal, pluripotency, an inherent resistance to chemo- and radiotherapy, the presence certain epigenetic alterations, as well higher tumorigenicity comparison with general population cells. A combination these features highlights high-priority target during treatment. has been confirmed multiple malignancies, including pancreatic ductal adenocarcinoma, entity that is known for its dismal prognosis. As aggressive course carcinoma partly attributable treatment resistance, could contribute adverse outcomes. aim this review summarize current information regarding markers molecular adenocarcinoma therapeutic options remove them.
Language: Английский
Citations
15
Gastroenterology, Journal Year: 2023, Volume and Issue: 166(1), P. 139 - 154
Published: Sept. 20, 2023
The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is linked to the presence cancer stem-like cells (CSCs) that respond poorly current chemotherapy regimens. epigenetic mechanisms regulating CSCs are currently insufficiently understood, which hampers development novel strategies for eliminating CSCs.
Language: Английский
Citations
11
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: April 27, 2024
The lethality, chemoresistance and metastatic characteristics of cancers are associated with phenotypically plastic cancer stem cells (CSCs). How the non-cell autonomous signalling pathways cell-autonomous transcriptional machinery orchestrate cell-like CSCs is still poorly understood. Here we use a quantitative proteomic approach for identifying secreted proteins in pancreatic cancer. We uncover that E2F1/4-pRb/RBL2 axis balances non-cell-autonomous healthy ductal but becomes deregulated upon KRAS mutation. E2F1 E2F4 induce whereas pRb/RBL2 reduce WNT ligand expression (e.g. WNT7A, WNT7B, WNT10A, WNT4) thereby regulating self-renewal, invasiveness both PDAC breast cancer, fibroblast proliferation. Screening epigenetic enzymes identifies GCN5 as regulator deposits H3K9ac onto promoters enhancers. Collectively, paracrine controlled by E2F-GCN5-RB diverse this could be therapeutic target eliminating CSCs.
Language: Английский
Citations
4
MedComm, Journal Year: 2024, Volume and Issue: 5(8)
Published: Aug. 1, 2024
Abstract Currently, cancer is still a leading cause of human death globally. Tumor deterioration comprises multiple events including metastasis, therapeutic resistance and immune evasion, all which are tightly related to the phenotypic plasticity especially epithelial–mesenchymal (EMP). cells with EMP manifest in three states as transition (EMT), partial EMT, mesenchymal–epithelial transition, orchestrate switch heterogeneity tumor via transcriptional regulation series signaling pathways, transforming growth factor‐β, Wnt/β‐catenin, Notch. However, due complicated nature EMP, diverse process not fully understood. In this review, we systematically conclude biological background, regulating mechanisms well role therapy response. We also summarize range small molecule inhibitors, immune‐related approaches, combination therapies that have been developed target for outstanding EMP‐driven deterioration. Additionally, explore potential technique EMP‐based mechanistic investigation research, may burst vigorous prospects. Overall, elucidate multifaceted aspects progression suggest promising direction treatment based on targeting EMP.
Language: Английский
Citations
4
Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 102018 - 102018
Published: March 1, 2025
Highlights•Neoadjuvant PARPi + ARSi shows efficacy with manageable toxicity in high-risk PCa•Biallelic HRR/BRCA2 alterations correlate faster PSA decline•Post-treatment analysis reveals MYC suppression and reduced proliferation-related pathways•Drug-tolerant persister cells exhibit enhanced EMT AP-1 activationSummaryPreclinical studies suggest synergistic effects between androgen receptor inhibitors poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors. This phase 2 trial (NCT05223582) evaluates neoadjuvant fuzuloparib plus abiraterone 35 treatment-naive men localized prostate cancer. Patients receive six cycles of therapy followed by radical prostatectomy. Primary endpoints are pathological complete response (pCR) minimal residual disease (MRD, ≤5 mm). The combined pCR/MRD rate is 46% (95% confidence interval [CI]: 29%–63%), a 53% 2-year biochemical progression-free survival rate. Grade ≥3 adverse events occur 23% patients. Biallelic homologous recombination repair/BRCA2 prostate-specific antigen decline. Post-treatment genomic analyses reveal amplification proliferation markers, alongside activated epithelial-mesenchymal transition/activator protein 1 (AP-1) pathways. meets its primary endpoint, demonstrating feasibility preliminary efficacy, while exploratory biomarkers may guide future studies.Graphical abstract
Language: Английский
Citations
0
Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)
Published: March 18, 2025
In the domain of addressing cancer resistance, challenges such as limited effectiveness and treatment resistance remain persistent. Hypoxia is a key feature solid tumors strongly associated with poor prognosis in patients. Another significant portion development acquired drug attributed to tumor stemness. Cancer stem cells (CSCs), small cell subset self-renewal proliferative abilities, are crucial for initiation, metastasis, intra-tumoral heterogeneity. Studies have shown association between hypoxia CSCs context resistance. Recent studies reveal strong link stemness, which together promote survival progression during treatment. This review elucidates interplay CSCs, well their correlation therapeutic drugs. Targeting pivotal genes stemness holds promise novel therapeutics combat
Language: Английский
Citations
0
Oncogene, Journal Year: 2025, Volume and Issue: unknown
Published: April 14, 2025
Language: Английский
Citations
0