Elevated BEAN1 expression correlates with poor prognosis, immune evasion, and chemotherapy resistance in rectal adenocarcinoma

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 14, 2024

Language: Английский

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Induction immunochemotherapy followed by definitive chemoradiotherapy for unresectable locally advanced non‐small cell lung cancer: a multi‐institutional retrospective cohort study

MedComm, Journal Year: 2024, Volume and Issue: 5(3)

Published: March 1, 2024

Abstract This study aimed to evaluate the efficacy and safety of induction immunochemotherapy followed by definitive chemoradiotherapy (CRT) for unresectable locally advanced non‐small cell lung cancer (LA‐NSCLC). We identified stage III NSCLC patients who received immunochemotherapy. Overall survival (OS) progression‐free (PFS) were primary endpoints. From February 2019 August 2022, 158 enrolled. Following completion immunochemotherapy, objective response rate (ORR) disease control (DCR) 52.5% 83.5%, respectively. The ORR CRT was 73.5%, representing 68.4% total cohort. median PFS 17.8 months, OS 41.9 significantly higher than in alone ( p < 0.001). Patients with concurrent demonstrated markedly improved = 0.012) 0.017) those undergoing sequential CRT. Additionally, a programmed‐death ligand 1 (PD‐L1) expression 50% or showed elevated ORRs (72.2% vs. 47.2%, 0.011) superior (median 44.8 28.6 0.004) compared PD‐L1 below 50%. Hematologic toxicities severe adverse events (grade ≥ 3) encountered, no unforeseen treatment‐related toxicities. Thus, encouraging tolerable LA‐NSCLC.

Language: Английский

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Chemotherapy-free radiotherapy combined with immune checkpoint inhibitors: a new regimen for locally advanced non-small cell lung cancer?

Cancer Biology and Medicine, Journal Year: 2024, Volume and Issue: 20(12), P. 1035 - 1046

Published: Feb. 5, 2024

Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC). The efficacy of pembrolizumab without chemotherapy stage IV NSCLC has incited interest similar approaches for LA-NSCLC. Several recent investigations involving synergistic potential combined radiotherapy (iRT) have generated encouraging results. This review discusses existing studies and prospective directions chemotherapy-free iRT strategies Although initial findings shown promising efficacy, we must consider methodologic limitations current myriad challenges that accompany implementation iRT. These include determining optimal dose fractionation, precise target volume delineation, identification additional suitable patient cohorts. Furthermore, feasibility as a novel treatment modality select LA-NSCLC is contingent upon validation through randomized phase III trials.

Language: Английский

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Innovative dual-gene delivery platform using miR-124 and PD-1 via umbilical cord mesenchymal stem cells and exosome for glioblastoma therapy

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: March 25, 2025

Abstract Addressing the challenges of identifying suitable targets and effective delivery strategies is critical in pursuing therapeutic solutions for glioblastoma (GBM). This study focuses on potential microRNA-124 (miR-124), known its tumor-suppressing properties, by investigating ability to target key oncogenic pathways GBM. The results reveal that CDK4 CDK6—cyclin-dependent kinases promote cell cycle progression—are significantly overexpressed GBM brain samples, underscoring their role tumor proliferation them as miR-124 intervention. However, delivering miRNA-based therapies remains a major obstacle due instability RNA molecules difficulty achieving targeted, efficient delivery. To address these issues, this research introduces an innovative, non-viral dual-gene platform utilizes umbilical cord mesenchymal stem cells (UMSCs) exosomes transport programmed death protein-1 (PD-1). efficacy system was validated using orthotopic model, which closely mimics microenvironment seen patients. Experimental demonstrate UMSC/ miR-124-PD-1 complex successfully induce apoptosis cells, inhibiting growth. Notably, treatments show minimal cytotoxic effects normal glial highlighting safety selectivity. Moreover, highlights immunomodulatory properties exosomes, enhancing activation immune such T dendritic while reducing immunosuppressive populations like regulatory myeloid-derived suppressor cells. orchestrated UMSCs showcased targeted inhibition positive modulation, emphasizing promising approach

Language: Английский

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Chemotherapy-Free Treatment with Radiotherapy and Immunotherapy for Locally Advanced Non-Small Cell Lung Cancer

Cancers, Journal Year: 2025, Volume and Issue: 17(9), P. 1524 - 1524

Published: April 30, 2025

Background: Concurrent chemoradiotherapy (CRT) followed by immunotherapy is a standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC), yet many patients are ineligible due to treatment-related toxicity or poor functional status. Chemotherapy-free approaches using radiotherapy (RT) and may offer safer equally effective alternative in select patient populations. Methods: A comprehensive literature review was conducted PubMed, Google Scholar, relevant conference proceedings focusing on trials between 2000 2024. Studies investigating chemotherapy-free regimens combining RT LA-NSCLC were analyzed, with emphasis clinical outcomes, biomarker use, sequencing, radiation dose/fractionation, safety. Results: Multiple Phase I/II reported promising efficacy one-year progression-free survival (PFS) ranging from 39% 76%. Toxicity generally acceptable, though higher-grade adverse events more frequent older, frail Trials integrating PD-L1 expression, tumor mutational burden (TMB), circulating DNA (ctDNA) showed potential improved stratification. Variation timing (induction, concurrent, consolidation) schedules highlight the need optimization. Conclusions: represent strategy LA-NSCLC, especially those that CRT. Biomarker-driven selection rational integration of critical improving outcomes. Randomized warranted establish safety these emerging approaches.

Language: Английский

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The role of chemoradiotherapy and immunotherapy in stage III NSCLC

Pathology & Oncology Research, Journal Year: 2024, Volume and Issue: 30

Published: April 19, 2024

Locally advanced non-small lung cancer encompasses a diverse range of tumors. In the last few years, treatment stage III unresectable has evolved significantly. The PACIFIC trial opened new therapeutic era in locally NSCLC, establishing durvalumab consolidation therapy as standard care worldwide. A careful evaluation this type and discussion management these patients within multidisciplinary team represents crucial step defining best strategy for each patient. For definitive concurrent chemoradiotherapy (CCRT) was historically recommended with 5-year survival rate ranging from 20% to 30%. study conducted 2017 compared use maintenance anti-PD-L1 monoclonal antibody placebo NSCLC who had not experienced disease progression. prospective, randomized, phase III. administration medication cell (NSCLC) demonstrated notable improvement overall survival. Multiple clinical trials are currently exploring various immune checkpoint inhibition regimens enhance efficacy cancer. Our goal is offer an up-to-date summary planned options, focusing on significant obstacles prospects post-PACIFIC era.

Language: Английский

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Fraction Dose Escalation of Hypofractionated Radiotherapy with Concurrent Chemotherapy and Subsequent Consolidation Immunotherapy in Locally Advanced Non–Small Cell Lung Cancer: A Phase I Study

Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 30(13), P. 2719 - 2728

Published: April 23, 2024

Abstract Purpose: This phase I trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients locally advanced non–small cell lung cancer. Patients Methods: Split-course hypo-RT hypoboost was administered at three levels (DL), using a stepwise dose-escalation protocol. The sophisticated esophagus-sparing technique implemented restrict esophagus. who did not experience disease progression or unresolved ≥grade 2 (G2+) toxicities after RT received cICI. Each DL treat six patients. MTFD defined as highest which ≤2 were treated experienced treatment-related G3+ toxicity ≤1 patient G4+ within 12 months post-RT. Results: Eighteen enrolled, in each DL. All completed chemotherapy, 16 (88.9%) least one infusion cICI, median 10 infusions. Within 12-month assessment period, DL1 G3 pneumonitis, DL3 developed tracheobronchitis. reached. objective response rate 100%. With follow-up 20.9 months, 1-year overall survival progression-free rates 94.4% 83.3%, respectively. Conclusions: Utilizing split-course approach, 5 Gy total 60 Gy, well yielded promising outcomes.

Language: Английский

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Integration of Circulating Tumor DNA and Metabolic Parameters on ¹⁸F‐Fludeoxyglucose Positron Emission Tomography for Outcome Prediction in Unresectable Locally Advanced Non‐Small Cell Lung Cancer

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 16, 2025

Abstract This prospective study explores the prognostic value of circulating tumor DNA (ctDNA) and positron emission tomography/computed tomograpy (PET/CT) in unresectable locally advanced non‐small cell lung cancer (LA‐NSCLC) treated with definitive chemoradiotherapy (CRT). The discovery set includes 62 patients, baseline 53 post‐CRT plasma samples. PET/CT is performed at baseline, 33 patients undergo mid‐treatment scans after 40 Gy. Baseline ctDNA detected 71.0% patients. Pre‐treatment concentration correlates total metabolic volume (TMTV) ( p < 0.001) lesion glycolysis (TLG) = but not treatment response or survival. However, undetectable low TMTV show significantly longer progression‐free survival (PFS) (34.2 vs 10.1 months, 0.027). Post‐CRT, 47.2% while 0.005) variant allele frequency (VAF) decline. Undetectable associates PFS overall (OS) 0.001). Higher ∆TMTV improved OS. Similar findings were obtained a test 19 These results highlight as robust markers, potentially identifying who may forgo ICI consolidation.

Language: Английский

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Current Research in Drug-Free Cancer Therapies

Bioengineering, Journal Year: 2025, Volume and Issue: 12(4), P. 341 - 341

Published: March 26, 2025

Cancer treatment has historically depended on conventional methods like chemotherapy, radiation, and surgery; however, these strategies frequently present considerable limitations, including toxicity, resistance, negative impacts healthy tissues. In addressing challenges, drug-free cancer therapies have developed as viable alternatives, utilizing advanced physical biological to specifically target tumor cells while reducing damage normal This review examines several strategies, such high-intensity focused energy beams, nanosecond pulsed electric fields, photothermal therapy well the use of inorganic nanoparticles promote selective apoptosis. We also investigate significance targeting microenvironment, precision medicine, immunotherapy in progression personalized therapies. Although approaches demonstrate significant promise, challenges scalability, safety, regulatory obstacles must be resolved for clinical application. paper presents an overview current research therapies, emphasizing recent advancements, underlying scientific principles, steps required implementation.

Language: Английский

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Neoadjuvant immunotherapy for NSCLC: superior combination strategies, optimal treatment cycles, and predictive indicators from a Bayesian meta-analysis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 27, 2025

Background Neoadjuvant immune checkpoint inhibitors (ICIs) have emerged as a promising treatment strategy for resectable non-small cell lung cancer (NSCLC). However, optimal combination strategies, cycles, and predictive indicators long-term outcomes remain unclear. This study aimed to evaluate the efficacy of various neoadjuvant ICI-based therapies in NSCLC, identify cycles immunochemotherapy, assess prognostic value pathological complete response (pCR) major (MPR) event-free survival (EFS). Methods A systematic literature search was conducted PubMed, EMBASE, Cochrane CENTRAL, Web Science, including studies published up October 2024. Bayesian models were used analyze different combinations, impact immunochemotherapy on MPR pCR, examine pCR EFS. Results Data from 34 included, consisting 32 single-arm (reported 26 papers) 8 RCTs, involving 4,593 patients. Immunochemotherapy combined with anti-angiogenesis agents most effective strategy, significantly improving both pCR. No significant improvement observed when number exceeded 3 cycles. Both strong predictors showed stronger negative correlation event risk compared log (HR) -2.110 (95% CI: -4.150, -0.071) MPR, -1.665 -2.419, -0.992) Conclusion appears be highly NSCLC. Three demonstrated this study. are valuable EFS, showing value. These findings offer important insights optimizing strategies informing clinical decision-making Systematic review registration PROSPERO, identifier CRD42024592346.

Language: Английский

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