ABSTRACT Background Cancer and its treatments are linked to accelerated biological aging, which may contribute to late adverse health outcomes in cancer survivors. Aims This scoping review evaluated biomarker‐defined aging in adult cancer populations, focusing on associations with treatment exposures and the effectiveness of interventions intended to mitigate accelerated biological aging. Methods We searched MEDLINE, Embase, Cochrane Library, CINAHL, and Web of Science for original studies in adults (≥ 18 years) survivors of cancer. Eligible studies included a comparison group and assessed biological aging using molecular or cellular biomarkers. Retrospective studies, pediatric studies, animal or in vitro studies, and non‐biomarker‐based studies were excluded. Two reviewers independently screened studies, with discrepancies resolved by a third reviewer. Results Among 1796 records, 44 studies met inclusion criteria. Most were prospective or randomized trials from North America and Europe, predominantly in breast cancer. Treatment exposures were commonly associated with increased epigenetic age acceleration, elevated senescence markers, and altered immune profiles; the effects may be more pronounced with intensive chemotherapy. Interventional trials ( n = 15) were of heterogenous quality with only eight phase 2/3 trials, and only seven studies enrolled more than 100 participants. Nearly all were conducted in solid tumors, except for one pilot study in myeloid malignancy. Lifestyle interventions generally did not change telomere length, although one large breast cancer trial showed reduced oxidative stress. Conclusions Current evidence supports an association between cancer treatment and multiple biological aging metrics, but biomarker validity, assay heterogeneity, and residual confounding remain important limitations. Furthermore, interventional data on preventing or reversing this acceleration remains limited and heterogeneous. The lack of consistent biomarker change in many trials may reflect short follow‐up durations and small sample sizes. Research is concentrated in breast cancer and high‐income countries, highlighting the need for adequately powered trials across diverse populations to identify strategies that preserve long‐term health.
ABSTRACT Aging is a progressive functional decline with increased susceptibility to human diseases. Among these age‐related diseases, adult acute myeloid leukemia (AML) is a fatal hematologic malignancy characterized by aggressive clonal expansion and arrested differentiation of myeloid progenitors. Although it is known that aging plays a crucial role in AML pathogenesis, treating this age‐related blood disease remains a huge challenge, which needs a deeper understanding of the mechanisms of aging in driving AML. This review updates recent advances on the relationship between aging and AML pathogenesis by focusing on the age‐related intrinsic and extrinsic factors. The aging of the hematopoietic system exhibits an expansion of phenotypic hematopoietic stem cells (HSCs), skewed differentiation to myeloid lineage, decreased repopulation ability, and altered clonal behaviors. We first discuss the role of aging in regulating the fate and fitness of HSCs, and summarize how aging contributes to the accumulation of genomic alterations and clonal hematopoiesis. In the following, epigenetic and metabolic alterations in hematopoietic cells and AML pathogenesis with aging are emphasized, and the aging‐related changes in extrinsic elements are also reviewed. Finally, we discuss the potential for aging intervention in treating hematopoietic malignancies. Overall, this review provides a comprehensive summary of the aging‐associated intrinsic and extrinsic factors for AML pathogenesis. Targeting these aging‐associated alterations in HSCs may provide new opportunities for AML intervention.
ABSTRACT Introduction Lung cancer remains the leading cause of cancer‐related mortality worldwide. Despite advances in treatment, postoperative recurrence rates in early‐stage and locally advanced non‐small cell lung cancer (NSCLC) remain substantial. Prognostic models may support risk stratification and guide posttreatment management. Objective To systematically identify and compare prognostic models predicting survival and recurrence outcomes in patients with NSCLC treated with curative intent. Methods This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. MEDLINE, EMBASE, and the Cochrane Library were searched from inception to November 29, 2022, with an updated search to capture newly published studies. Eligible studies reported quantitative performance measures of prognostic models predicting recurrence‐free survival (RFS), cancer‐specific survival (CSS), or overall survival (OS) in patients with curatively treated NSCLC. Data extraction followed the CHARMS checklist, and risk of bias was assessed using the PROBAST tool. The review protocol was registered with PROSPERO (CRD42021226091). Results Of 6369 screened records, 40 studies met inclusion criteria. Most models employed Cox proportional hazards regression and varied widely in predictor selection. Common predictors included age (n = 40), sex (n = 40), and tumor characteristics (n = 36). Radiomic features were incorporated in 11 models and were associated with improved discrimination. Reported model performance ranged from poor to excellent (AUROC 0.5–0.9), with most models demonstrating acceptable to good discrimination (AUROC > 0.7). The highest reported 3‐year OS AUROC was 0.90 (95% CI: 0.85–0.95). However, only four models underwent external validation, and reporting of calibration and other performance metrics was inconsistent. Conclusion Prognostic models for survival and recurrence in resected NSCLC frequently demonstrate good discrimination but are limited by inadequate external validation and variable reporting. Future research should prioritize transparent model development, robust validation, and clinical usability to improve posttreatment decision‐making.
ABSTRACT Background Nucleophosmin (NPM1), a multifunctional nucleolar protein, plays critical roles in ribosome biogenesis, chromatin organization, and genome stability. In one‐third of adult acute myeloid leukemia (AML) cases, mutations in NPM1, most frequently a 4‐bp insertion in exon 12 generates an aberrant nuclear export signal in C‐terminus, resulting in the cytoplasmic mislocalization of NPM1 (NPM1c). NPM1c defines a distinct molecular entity characterized by aberrant activation of HOXA/B clusters and MEIS1, which sustain an oncogenic transcriptional program. Aims This review aims to summarize recent advances in the molecular mechanisms of NPM1c‐driven leukemogenesis and discuss its implications for clonal evolution and targeted therapies. Methods and Results Recent findings revealed that NPM1c forms neomorphic chromatin‐bound condensates with the Menin–MLL complex, XPO1, and the super‐elongation complex, amplifying leukemogenic transcriptional hubs while suppressing HDAC activity. Within the framework of age‐associated clonal hematopoiesis (CH), NPM1c acts as a late gatekeeping mutation that transforms preleukemic clones harboring early epigenetic lesions in DNMT3A, TET2, or IDH1/2 into overt AML cells. Insights from mouse models support this hierarchical evolution and underscore the requirement for cooperating mutations, such as FLT3‐ITD. Emerging therapies including Menin–MLL, XPO1, DOT1L, HBO1, and ENL inhibitors target NPM1c‐driven HOX/MEIS1 dysregulation, whereas early intervention at the CH stage in hematopoietic stem and progenitor cells (HSPCs) harboring IDH or DNMT3A mutations offers a promising preventive strategy. Conclusion This review integrates mechanistic advances from biochemistry, genetic and epigenetic regulation, and clonal evolution to provide a unified model of NPM1c‐mediated leukemogenesis and highlights future directions for precision therapy in AML.
ABSTRACT Objectives This prospective study aimed to assess the outcomes of laparoscopic sphincter‐preserving surgery in elderly patients with rectal cancer. Methods This study included patients over 65 years old with rectal cancer who underwent laparoscopic sphincter‐preserving surgery between 2015 and 2018. Patients with prior malignancies or abdominal surgeries were excluded. All patient data were collected, and the follow‐up was conducted over 5 years. Results A total of 78 patients underwent surgery with a median follow‐up of 65 months. The overall survival was approximately 80% at 3 years and 70% at 5 years. Notably, nearly half of the total deaths (11 out of 24) resulted from non‐cancer causes, including COVID‐19 and other comorbidities. Advanced T‐stage and tumor invasion were identified as the primary factors significantly associated with increased recurrence and mortality in univariate analyses. However, these factors did not remain statistically significant in multivariate models, likely due to the limited sample size of this geriatric cohort. Conclusion Laparoscopic sphincter‐preserving surgery is feasible for elderly patients, achieving a 70% 5‐year survival rate. However, the high recurrence risk in advanced T‐stage and invasive cases underscores the need for personalized geriatric protocols and more aggressive preoperative strategies for high‐risk subgroups.
