Enhancing precision in cancer treatment: the role of gene therapy and immune modulation in oncology

Frontiers in Medicine, Год журнала: 2025, Номер 11

Опубликована: Янв. 13, 2025

Gene therapy has long been a cornerstone in the treatment of rare diseases and genetic disorders, offering targeted solutions to conditions once considered untreatable. As field advances, its transformative potential is now expanding into oncology, where personalized therapies address immune-related complexities cancer. This review highlights innovative therapeutic strategies, including gene replacement, silencing, oncolytic virotherapy, CAR-T cell therapy, CRISPR-Cas9 editing, with focus on their application both hematologic malignancies solid tumors. CRISPR-Cas9, revolutionary tool precision medicine, enables precise editing cancer-driving mutations, enhancing immune responses disrupting tumor growth mechanisms. Additionally, emerging approaches target ferroptosis—a regulated, iron-dependent form death—offering new possibilities for selectively inducing death resistant cancers. Despite significant breakthroughs, challenges such as heterogeneity, evasion, immunosuppressive microenvironment (TME) remain. To overcome these barriers, novel like dual-targeting, armored cells, combination checkpoint inhibitors ferroptosis inducers are being explored. rise allogeneic “off-the-shelf” offers scalable more accessible options. The regulatory landscape evolving accommodate advancements, frameworks RMAT (Regenerative Medicine Advanced Therapy) U.S. ATMP (Advanced Therapy Medicinal Products) Europe fast-tracking approval therapies. However, ethical considerations surrounding CRISPR-based editing—such off-target effects, germline ensuring equitable access—remain at forefront, requiring ongoing oversight. Advances non-viral delivery systems, lipid nanoparticles (LNPs) exosomes, improving safety efficacy By integrating innovations addressing concerns, poised revolutionize cancer treatment, providing durable, effective,

Язык: Английский

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Therapy related acute myeloid leukemia secondary to CAR-T therapy in refractory/relapsed multiple myeloma patient showing poor prognosis

Annals of Hematology, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

There has been a growing concern regarding the adverse events including hematological malignancies which occurring in later stages following CAR-T immunotherapy. Here, we presented case of secondary MDS/AML immunotherapy our center. This refractory/relapsed MM patient who received systematic treatment chemotherapy and targeted drug as well autologous stem cell transplantation was developed into MDS AML especially after BCMA immunotherapy, even allogeneic hematopoietic could not save very poor prognosis. Further meta-analysis also demonstrated considerable heterogeneity through total studies CD19 subgroups. In conclusion, it is imperative that long-term close monitoring for patients undergoing with particular attention to potential development malignancies.

Язык: Английский

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From clinical observations to molecular insights: Decoding immune checkpoint inhibitors‐induced prostatitis

View, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Abstract Immune checkpoint inhibitors (ICIs) have dramatically transformed cancer treatment; however, their impact on the male reproductive system remains poorly understood. This study aims to elucidate incidence, risk factors, and molecular mechanisms underlying ICI‐associated prostatitis. We conducted an analysis of prostatitis utilizing U.S. Food Drug Administration Adverse Event Reporting System (FAERS) database evaluated through application reporting odds ratio. A mouse model ICI treatment was developed, subsequent transcriptomic changes in prostate tissue were investigated using high‐throughput sequencing. Hematoxylin eosin staining, immunohistochemistry, Von Frey testing, enzyme‐linked immunosorbent assay employed confirm ICI‐induced further delineate its mechanisms. Additionally, we therapeutic potential specifically targeting interleukin‐6 (IL‐6) extracellular signal‐regulated kinase (ERK) signaling pathways. FAERS demonstrated a statistically significant positive correlation between ( p < .05). In murine model, induced elevated inflammatory response tissue, characterized by enhanced cell infiltration upregulated expression IL‐6 tumor necrosis factor‐alpha. Transcriptomic revealed activation multiple inflammation‐related pathways following (false discovery rate 0.05). Targeted inhibition or ERK significantly attenuated symptoms, resulting improved pathology decreased factor .01). delineates characteristics prostatitis, thereby establishing theoretical foundation for development prevention strategies. modulation may present novel interventions thus warranting clinical validation.

Язык: Английский

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From bench to bedside: elucidating VEGF(R) inhibitor-related heart failure in cancer treatment

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 23, 2025

Abstract Background Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors play a pivotal role in treating various tumors; however, the clinical characteristics molecular mechanisms of their associated heart failure (HF) remain incompletely understood. Methods We investigated epidemiological or VEGFR [VEGF(R)i]-related (VirHF) using global pharmacovigilance database Vigibase. The phenotypic features VirHF were characterized VEGF(R)i-treated mouse models through combination echocardiography, histopathological analysis, transcriptome sequencing. Furthermore, we performed retrospective analysis cardiac function parameters patients undergoing VEGF(R)i treatment at local hospitals. Results In 1871 cases, elderly (≥ 65 years) female subjects demonstrated an elevated risk occurrence. Experimental studies mice revealed that both acute chronic administration resulted reduced left ventricular EF, cardiomyocyte hypertrophy, myocardial fibrosis. Transcriptomic identified significant dysregulation multiple key signaling pathways, including DNA repair (R = 0.46), mitochondrial ATP synthesis 0.39), glycogen metabolism regulation 0.45), proteasome-mediated protein degradation 0.45). Moreover, upregulation was observed inflammatory specifically those involving IL-1, IL-6, TNF-α, IRF3/IRF7-mediated immune responses. Clinical cohort analyses elevations injury biomarkers (NT-proBNP, CK-MB, cTnT) mediators (CRP) following administration. Conclusions Our findings present first comprehensive characterization elucidate its underlying mechanisms, thereby providing theoretical framework for optimizing safety therapy.

Язык: Английский

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Second primary malignancies following CAR T-cell therapy in patients with hematologic malignancies

Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)

Опубликована: Март 18, 2025

Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the management of patients with relapsed/refractory (R/R) hematologic malignancies, including B-cell lymphomas and multiple myeloma (MM). While data pertaining to efficacy toxicity associated CAR-T have been widely reported, there are limited on long-term complications. We retrospectively analyzed 246 treated for R/R lymphoma (n = 228) MM 18) at Ohio State University from 2016 2022, a minimum two years follow-up. The median age was 66 years, number prior treatments four. With follow-up 38 months (range 11–66), 21 (8.5%) developed second primary malignancy (SPM), non-melanoma skin cancer being most common (52%), followed by malignancies (33%) non-skin solid tumors (14%). Squamous cell carcinoma accounted 38% cancers, while myelodysplastic syndrome acute myeloid leukemia were predominant malignancies. Solid included bladder, prostate, breast cancer. distinct pattern SPMs suggests potential CAR-T-related risks, warranting vigilant post-treatment surveillance. Further studies necessary elucidate underlying mechanism predictive factors guide SPM risk in survivors.

Язык: Английский

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Risk comparison of adverse reactions between gemcitabine monotherapy and gemcitabine combined with albumin-bound paclitaxel in pancreatic cancer: insights from the FDA Adverse Event Reporting System (FAERS) database

BMC Pharmacology and Toxicology, Год журнала: 2025, Номер 26(1)

Опубликована: Март 19, 2025

Pancreatic cancer (PC) is a highly aggressive malignancy with limited treatment options. Although gemcitabine monotherapy (G treatment) has long been standard treatment, combination therapies, such as albumin-bound paclitaxel (AG treatment), have shown improved outcomes and were approved by the FDA for PC. However, AG also associated increased adverse events (AEs), which remain inadequately evaluated in real-world settings. We utilized Adverse Event Reporting System (FAERS) to conduct large-scale pharmacovigilance analysis comparing safety profiles of G treatments By analyzing event data from third quarter 2013 second 2024 quantifying AE signals reporting odds ratio (ROR) proportional (PRR) methods, we compared risk AEs between groups. Time onset (TTO), subgroup logistic regression analyses performed. The study revealed higher proportion male (n = 2307, 54.1%) elderly patients (age ≥ 65years, n 2172, 50.9%) group group. found 17 preferred terms positive at top 50 common AEs, especially gastrointestinal blood systems. Cardiac neurological needed be vigilant. Biliary sepsis infectious enterocolitis newly identified deserve attention. Median TTO was 34 (IQR: 8-103) days (G) 41 10–104) (AG), most occurring within first month (48.3% 44%). Subgroup that using had highest immune-mediated hepatitis (ROR 23.51, 95% CI 3.21–172.1), while elevated risks presyncope 24.84, 3.40–181.28) falls 18.60, 2.53–136.97). Logistic showed higher-risk fatal males (adjusted OR 1.42, 1.15–1.76, P < 0.01) 1.36, 1.10–1.69, 0.01). This research offers critical insights settings, emphasizing heightened informing clinical decision-making PC treatment.

Язык: Английский

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Adverse drug reaction patterns of GLP‐1 receptor agonists approved for obesity treatment: Disproportionality analysis from global pharmacovigilance database

Diabetes Obesity and Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

This study aims to compare adverse drug reaction patterns of liraglutide, semaglutide and tirzepatide-glucagon-like peptide-1 receptor agonists (GLP-1 RAs) approved for anti-obesity medications-to evaluate their real-world safety. disproportionality analysis utilized a case-control design with VigiBase. The focused on reports events associated tirzepatide, selected based warnings in the US Food Drug Administration approval labels each drug. Data were restructured using unique identifiers differentiate individuals affected by reactions. Multivariable logistic regression models estimated adjusted reporting odds ratios (aRORs) 95% confidence intervals (CIs) assess association between various GLP-1 RAs, adjusting age, sex, region, reporter qualification, year concomitant medication. information component (IC) was analysed, signals reactions considered significant only when both aROR IC statistically significant. Our targeted included 24 725 21 454 11 538 tirzepatide. Tirzepatide had fewer compared other two drugs, its pharmacovigilance strength lowest. Semaglutide, however, significantly several unusual events, including suicidal ideation behaviour (IC, 1.53 [IC025, 1.28]; aROR, 2.52 [95% CI, 2.18-2.93]), hair loss 0.78 0.63]; 1.42 1.30-1.55]) vision 1.27 1.13]; 1.80 1.66-1.97]). findings emphasize need cautious prescribing further research ensure safe use these medications.

Язык: Английский

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NK Cell Senescence in Cancer: From Molecular Mechanisms to Therapeutic Opportunities

Aging and Disease, Год журнала: 2025, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2025

P Natural killer (NK) cells function as crucial effectors in the innate immune response against tumors. Nevertheless, NK cell senescence, characterized by phenotypic and functional changes, substantially compromises their antitumor response. This review provides a comprehensive summary of molecular mechanisms governing senescence its implications for cancer immunotherapy. We propose refined definition based on distinct biomarkers, including elevated CD57 expression, reduced cytotoxicity, altered cytokine secretion. Moreover, we investigate complex interactions between tumor microenvironment (TME) highlighting influence chronic inflammation, immunosuppressive cytokines, persistent antigenic stimulation. Additionally, this underscores potential utility senescent biomarkers assessing efficacy examines adverse effects Lastly, summarize current approaches to mitigate such gene editing techniques modulation, which may enhance cell-based immunotherapies. By establishing framework understanding within TME, aims guide future research development innovative therapeutic strategies targeting improve immunotherapy outcomes.

Язык: Английский

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Worldwide burden of antidiabetic drug-induced sarcopenia: An international pharmacovigilance study

Archives of Gerontology and Geriatrics, Год журнала: 2024, Номер 129, С. 105656 - 105656

Опубликована: Окт. 11, 2024

Язык: Английский

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Genetic and immunological features of immune deficiency and dysregulation‐associated lymphoproliferations and lymphomas as a basis for classification

Histopathology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 22, 2024

Immune deficiency and dysregulation‐associated lymphoproliferative disorders lymphomas (IDD‐LPDs) encompass a heterogeneous clinical pathological spectrum of that range from indolent lymphoproliferations to aggressive lymphomas. They arise in variety settings are associated with oncogenic viruses such as the Epstein–Barr virus (EBV) Kaposi sarcoma‐associated herpesvirus/human herpes (KSHV/HHV8) some, but not all, cases. The recognition IDD‐LPDs distinct LPDs immune competent patients is essential tailor management options for affected patients. 5th edition World Health Organisation classification has introduced an integrated goal standardising diagnoses among different enhance decision support. In parallel, new knowledge field, particularly surrounding role tumour microenvironment, led clearer understanding complex pathogenesis how these features can be precisely harnessed therapeutic purposes. this perspective, we highlight need multidisciplinary decision‐making augment patient care well key areas where evolving concepts offer challenges opportunities management, research future iterations classification.

Язык: Английский

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