Journal of Hazardous Materials, Год журнала: 2024, Номер 480, С. 136351 - 136351
Опубликована: Ноя. 1, 2024
Язык: Английский
Drug Resistance Updates, Год журнала: 2024, Номер 78, С. 101170 - 101170
Опубликована: Ноя. 15, 2024
Язык: Английский
Процитировано
24
Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)
Опубликована: Май 2, 2024
Abstract Anticancer immune surveillance and immunotherapies trigger activation of cytotoxic cytokine signaling, including tumor necrosis factor-α (TNF-α) TNF-related apoptosis-inducing ligand (TRAIL) pathways. The pro-inflammatory TNF-α may be secreted by stromal cells, tumor-associated macrophages, cancer indicating a prominent role in the microenvironment (TME). However, tumors manage to adapt, escape surveillance, ultimately develop resistance effects TNF-α. mechanisms which cells evade host immunity is central topic current research. Resistance mediated diverse molecular mechanisms, such as mutation or downregulation TNF/TRAIL receptors, well anti-apoptotic enzymes transcription factors. signaling also sphingosine kinases (SphK1 SphK2), are responsible for synthesis growth-stimulating phospholipid, sphingosine-1-phosphate (S1P). Multiple studies have demonstrated crucial S1P its transmembrane receptors (S1PR) both regulation inflammatory responses progression cancer. Considering that SphK/S1P/S1PR axis mediates resistance, this sphingolipid pathway mechanistic significance when considering immunotherapy-resistant malignancies. exact mechanism sphingolipids contribute evasion abrogation TNF-α-induced apoptosis remains largely unclear. This study reviews TNF-α-resistance with emphasis on pro-survival immunomodulatory sphingolipids. Inhibition SphK/S1P-linked branch facilitate reactivation pro-apoptotic TNF superfamily effects, although SphK/S1P inhibitors TME lymphocyte trafficking should thoroughly assessed future studies.
Язык: Английский
Процитировано
13
Cancer Communications, Год журнала: 2024, Номер 44(3), С. 408 - 432
Опубликована: Фев. 26, 2024
Chimeric antigen receptor T (CAR-T) therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignancies, but cancer-intrinsic mechanisms underlying resistance to CAR-T cells remain yet be fully understood. This study aims explore molecular determinants cancer cell sensitivity cell-mediated killing and provide a better understanding potential modulation improve efficacy.
Язык: Английский
Процитировано
12
ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown
Опубликована: Март 25, 2025
Breast cancer cells are characterized by heightened autophagy, which impairs tumor-associated antigen presentation and represents a significant barrier to the antitumor immunity. In this study, PD-L1-targeting autophagy modulator (PFC@CQ) is fabricated activate photoimmunotherapy against breast cancer. Specifically, hydrophobic photosensitizer protoporphyrin IX (PpIX) covalently linked peptide FFVLK sequence CLQKTPKQC, resulting in formation of an amphiphilic photosensitizer-peptide conjugate (PpIX-FFVLK-CLQKTPKQC, called PFC), capable encapsulating inhibitor chloroquine (CQ). PFC@CQ can not only facilitate targeted drug codelivery PD-L1-overexpressing cells, but also effectively disrupt their immune evasion blocking PD-1/PD-L1 pathway. Upon light irradiation, photodynamic therapy (PDT) induces tumor cell destruction immunogenic death (ICD), causing release damage-associated molecular patterns (DAMPs). Simultaneously, inhibit pathway mediate upregulation MHC-I, thereby enhancing presentation. This cascade immunomodulation promotes dendritic maturation CD8+ T activation, leading synergistic suppression both primary metastatic tumors. work introduces innovative modulation strategy with potent immunomodulatory capability, demonstrating potential trigger systemic responses through local treatment.
Язык: Английский
Процитировано
1
Frontiers in Pharmacology, Год журнала: 2024, Номер 15
Опубликована: Сен. 30, 2024
Cancer, the world’s second leading cause of death after cardiovascular diseases, is characterized by hallmarks such as uncontrolled cell growth, metastasis, angiogenesis, hypoxia, and resistance to therapy. Autophagy, a cellular process that can both support inhibit cancer progression, plays critical role in development progression. This involves formation autophagosomes ultimately fuse with lysosomes degrade components. A key regulator this Sirtuin 1 (SIRT1), which significantly influences autophagy. review delves into SIRT1 modulating autophagy its broader impacts on carcinogenesis. regulates crucial mediators, AMP-activated protein kinase (AMPK) mammalian target rapamycin (mTOR), effectively promoting or suppressing Beyond direct effects autophagy, SIRT1’s regulatory actions extend other processes, including apoptosis ferroptosis, thereby influencing tumor proliferation, chemotherapy responses. These insights underscore complex interplay between significant implications for Targeting associated pathways presents promising strategy manipulate treatment. underscores potential therapeutic target, opening new avenues enhancing treatment efficacy.
Язык: Английский
Процитировано
5
Translational Oncology, Год журнала: 2024, Номер 49, С. 102099 - 102099
Опубликована: Авг. 19, 2024
With the growing interest to harness cancer metabolism and energy reprogramming, this mini review aimed explain metabolic programming revealing mechanisms regarding treatment resistance. This summarized prominent reprogramming on macromolecules. In addition, explaining immune response resistance as well are briefly discussed. Finally, some prospects in MR for reversing drug highlighted.
Язык: Английский
Процитировано
3
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 588 - 588
Опубликована: Янв. 12, 2025
MEK inhibitors, such as trametinib, have shown therapeutic potential in head and neck squamous cell carcinoma (HNSCC). However, the factors influencing cancer sensitivity resistance to inhibition remain poorly understood. In our study, we observed that significantly reduced expression of MYC, a transcription factor critical for response. MYC overexpression markedly enhanced HNSCC cells evidenced by delayed wound healing colony formation. Cell cycle analysis revealed trametinib induced G1 phase arrest, whereas accelerated progression, with induction p27 p21 diminished decreases E2F1 phospho-Ser2/5 levels. Flow cytometry protein analyses demonstrated amplified trametinib-induced apoptosis DNA damage, elevated levels pro-apoptotic markers (p53, cleaved PARP, BIM) γH2AX. vivo xenograft models confirmed these findings, showing increased MYC-overexpressing tumors. Moreover, autophagy cells, resistance. Inhibiting further apoptotic death. These findings suggest play crucial roles HNSCC’s response inhibition. Combining may improve outcomes HNSCC.
Язык: Английский
Процитировано
0
Experimental Hematology and Oncology, Год журнала: 2025, Номер 14(1)
Опубликована: Фев. 1, 2025
Abstract Secretory autophagy is a classical form of unconventional secretion that integrates with the secretory process, relying on highly conserved autophagy-related molecules and playing critical role in tumor progression treatment resistance. Traditional responsible for degrading intracellular substances by fusing autophagosomes lysosomes. However, uses signaling to mediate specific regulate microenvironment (TME). Cytoplasmic are preferentially secreted rather than directed toward lysosomal degradation, involving various selective mechanisms. Moreover, released convey biological signals TME, inducing immune dysregulation contributing drug Therefore, elucidating mechanisms underlying essential improving clinical treatments. This review systematically summarizes current knowledge autophagy, from initiation secretion, considering inter-tumor heterogeneity, explores its across different types. Furthermore, it proposes future research directions highlights unresolved challenges.
Язык: Английский
Процитировано
0
Molecular Cancer, Год журнала: 2025, Номер 24(1)
Опубликована: Май 7, 2025
Cancer immunotherapy, encompassing both experimental and standard-of-care therapies, has emerged as a promising approach to harnessing the immune system for tumor suppression. Experimental strategies, including novel immunotherapies preclinical models, are actively being explored, while established treatments, such checkpoint inhibitors (ICIs), widely implemented in clinical settings. This comprehensive review examines historical evolution, underlying mechanisms, diverse strategies of cancer highlighting its applications ongoing advancements. The delves into essential components anticancer immunity, dendritic cell activation, T priming, surveillance, addressing challenges posed by evasion mechanisms. Key immunotherapeutic vaccines, oncolytic viruses, adoptive transfer, ICIs, discussed detail. Additionally, role nanotechnology, cytokines, chemokines, adjuvants enhancing precision efficacy were explored. Combination particularly those integrating immunotherapy with radiotherapy or chemotherapy, exhibit synergistic potential but necessitate careful management reduce side effects. Emerging factors influencing outcomes, heterogeneity, gut microbiota composition, genomic epigenetic modifications, also examined. Furthermore, molecular mechanisms therapeutic resistance analyzed, focus on contributions noncoding RNAs alterations, along innovative intervention strategies. emphasizes recent advancements, particular attention biomarker-driven approaches aimed at optimizing patient prognosis. Challenges immunotherapy-related toxicity, limited solid tumors, production constraints highlighted critical areas future research. Advancements personalized therapies delivery systems proposed avenues enhance treatment effectiveness accessibility. By incorporating insights from multiple disciplines, this aims deepen understanding application ultimately fostering more effective accessible solutions.
Язык: Английский
Процитировано
0
ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown
Опубликована: Май 7, 2025
Immune checkpoint blockade (ICB) therapy, represented by anti-PD-1/PD-L1 antibodies, is confronted with difficulties of unsatisfied response rates owing to the prevalence "cold" immune tumor microenvironment (TME) in most cancers. Blocking cytoprotective autophagy has emerged as a potential strategy remodel inflammatory TME. Nevertheless, dual roles progression, coupled poor pharmacokinetic properties small-molecule inhibitors, significantly restrict clinical applications. To address these challenges, low-intensity focused ultrasound (LIFU) responsive phase-change nanodroplet delivery platform (SP@Lip-PEG) elaborately developed deliver specific inhibitor SAR405 for activating typical tumor-resident cells. The PEG-modified nanodroplets effectively accumulate into site. Upon LIFU activation, SP@Lip-PEG transforms microbubbles through acoustic droplet vaporization (ADV) effects, enabling controlled release under imaging guidance. released triggered upregulation proinflammatory factors CCL5 and CXCL10 manipulation, creating an TME facilitate recruitment natural killer (NK) cells CD8+ T cells, along promoting dendritic cell (DC) maturation synergistically enhancing ICB efficacy. With high specificity controllable therapeutic process irradiation, this noninvasive, efficient, cost-effective drug vector opened new horizons conquering dilemma rescuing rates.
Язык: Английский
Процитировано
0