Acute myeloid leukemia (AML) exemplifies how malignant transformation can be driven by both epigenetic deregulation and genetic mutation. Aberrant DNA methylation, histone modifications, and chromatin remodelling cooperate to block myeloid differentiation, sustain leukemic self-renewal, and promote immune evasion. This review examines the molecular mechanisms underlying epigenetic dysregulation in AML and highlights recent advances in epigenetic and immune-based therapeutic strategies.

Recent studies have identified multiple druggable epigenetic regulators, including DNA methyltransferases, TET dioxygenases, histone methyltransferases and demethylases, and histone acetyltransferases and deacetylases. These discoveries have led to the development of hypomethylating agents, mutant IDH1/2 inhibitors, menin-MLL and DOT1L antagonists, EZH2 and LSD1 inhibitors, and class-specific HDAC inhibitors, several of which are approved or undergoing advanced clinical evaluation. Beyond reprogramming leukemic transcriptional networks, epigenetic therapies also remodel the immune microenvironment by influencing antigen presentation and immune checkpoint pathways, providing a rationale for combination approaches with antibody-drug conjugates, bispecific T-cell or NK-cell engagers, aptamer-directed therapeutics, vaccines, and CAR-T/NK cell therapies targeting CD33, CD123, FLT3, CLL-1, and other AML-associated antigens. The integration of epigenetic modulation with immunotherapeutic and precision medicine approaches represents a promising strategy to overcome disease heterogeneity and therapeutic resistance in AML. By bridging mechanistic insights with translational advances, clinical trial evidence, and emerging patent landscapes, this review highlights epigenetic dysregulation as both a fundamental driver of leukemogenesis and a clinically actionable therapeutic interface that may enable more rational treatment sequencing and personalized AML management.

While chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies, there are significant hurdles to overcome, such as antigen escape, T-cell exhaustion, limited persistence in the body, severe toxicities, manufacturing complexity, high costs, and low effectiveness in the treatment of solid tumors. There are many reviews describing novel CAR-T technologies, the evidence strength, clinical maturity and unmet translational risks of each are largely included in those reviews. This review highlights the ways in which next-generation engineering increases the safety, efficacy and programmability of CAR-T. The primary and authoritative clinical, regulatory and preclinical evidence on recent advances from 2022 to 2026 was carefully evaluated, including the quality and quality control of the evidence for each strategy. New innovations are Armored CARs, dual-target and logic-gated/synNotch systems, universal and switchable platforms, CRISPR/Cas9 and base/prime editing, allogeneic CAR-Ts, non-viral manufacturing, and lipid-nanoparticles in vivo CAR-T generation. Additionally, the engineering and combination approaches for the treatment of solid tumors with checkpoint inhibitors, radiotherapy, oncolytic viruses, nanotechnology, and artificial intelligence are discussed. An evidence-to-maturity framework separates the clinically proven methods from the emerging technologies and highlights some of the critical translation hurdles related to safety, immunogenicity, durability, manufacturing and scale. Precision Immunotherapy is becoming more and more possible with the next generation CAR-T engineering, however the validation and translational optimization of these cells is dominant to their eventual clinical use.

Sequential lymphoid neoplasms are rare and diagnostically challenging, with a variable clonal relationship. Here we present the case of a 59-year-old woman with mediastinal grey zone lymphoma (MGZL), who, shortly after achieving complete remission, developed a subsequent cutaneous neoplasm. Comparative molecular studies were performed using high-throughput sequencing (HTS), which demonstrated that both neoplasms shared high-allele-frequency EP300:p.P2333L and PTPRK:p.R532K variants. In addition, each neoplasm harboured private, mutually exclusive variants-NFKBIA:p.R245Sfs*39 and BTG2:c.142+5G>C in the MGZL and JAK1:p.Q562* and JAK1:p.G1097D in the skin. Integrating the clinical course with HTS, we diagnosed lymphomatoid papulosis and excluded relapse of the MGZL. Interestingly, the shared variants were likely germline rather than clonal, suggesting they created a permissive background predisposing to two independent transforming events along the B- and T-cell lineages. Molecular studies may help to reveal the genetic basis of composite lymphomas and to resolve diagnostically discordant, complex presentations.

Well-characterized patient-derived models of adult ependymoma (EPN) remain limited. We established a patient-derived organoid (PDO) platform from adult EPN and evaluated its histopathologic and immunophenotypic characteristics, transcriptomic relationship to parental tumors, and in vivo tumorigenicity.

Fresh surgical specimens from 22 adult patients with EPN were processed for PDO establishment. Tumor-PDO fidelity was assessed by histology and immunofluorescence. Three matched tumor-PDO pairs underwent RNA sequencing followed by paired differential-expression, gene-set enrichment, microenvironmental signature, and ESTIMATE analyses. Selected PDO models were further evaluated by subcutaneous and intracranial xenografting.

PDOs were successfully established from 20 of 22 specimens (90.9%). Established PDOs broadly retained parental tumor morphology and expression of major ependymoma-associated and neural/progenitor markers. Selected morphologic and immunophenotypic features remained detectable during prolonged culture. Transcriptomic profiling of three matched tumor-PDO pairs demonstrated high global expression similarity (Pearson r = 0.84-0.88) together with substantial culture-associated remodeling. Endothelial signatures and ESTIMATE-derived stromal scores were reduced in all three PDOs, whereas other immune and stromal signatures showed patient-specific changes. Paired transcriptomic analysis further identified enrichment of ribosome/translation and oxidative-phosphorylation programs in PDOs, accompanied by reduced cilia- and axoneme-associated programs. Selected PDO-derived models demonstrated tumorigenic capacity in subcutaneous and intracranial settings.

Adult EPN can be propagated efficiently as PDOs that retain selected tumor-associated features while undergoing measurable transcriptional and microenvironment-associated adaptation to ex vivo culture. Selected models also retained tumorigenic capacity in vivo. These models provide a complementary experimental platform for studying adult EPN biology.

Time toxicity has emerged as an important concept in oncology, reflecting the burden of time patients spend receiving care. However there is no consensus on how time toxicity is defined or measured. We conducted a systematic review to characterise the definitions and measurement methods.

MEDLINE, EMBASE, and Cochrane Library were searched from inception to 10th March 2026. Studies were included if they involved cancer patients and reported a definable measure of time-related burden associated with care. Data were extracted on study characteristics, sample size, data sources, and definitions of time toxicity.

Fifty-six studies were included. Most studies were observational (n = 45, 80.4%) and conducted in high-income countries, predominantly the United States (n = 29, 51.8%). Time toxicity was most commonly defined using direct healthcare time measures (n = 31, 55.4%), representing days involving healthcare encounters such as clinic visits, treatment sessions, hospitalisations, and emergency department visits. Time away from healthcare measures, including days alive and out of hospital or days at home, were used in 20 studies (35.7%). Healthcare process time incorporating non-clinical and logistical aspects of care were used in 5 studies (8.9%). No studies used patient-reported definitions of time toxicity. Most measures were derived from administrative, electronic health record, or clinical trial data, capturing healthcare utilisation but not patients' perceived burden or value of healthcare-related time.

Current definitions of time toxicity in cancer care are heterogeneous and predominantly system-derived, with minimal incorporation of patient-centred perspectives. We propose an empirical framework comprising three objective measurement domains: direct healthcare time, time away from healthcare, and healthcare process time-with patient-reported experience incorporated as an evidence-informed extension.

Cancer-associated autonomic dysfunction may suppress heart rate variability (HRV), yet no meta-analysis has pooled between-group differences in established HRV indices across cancer types. This review quantified HRV differences versus non-cancer controls, HRV-fatigue associations, and longitudinal HRV trajectories.

PubMed, MEDLINE, CINAHL, Embase, and the Cochrane Library were searched through March 2026. Adults with physician-confirmed malignancy and ECG- or PPG-based HRV were eligible. Because time-domain indices scale with recording length, the DerSimonian-Laird random-effects pool was restricted a priori to short-term resting recordings (5-10 min) with age-matched non-cancer controls (Part A); long-term ambulatory recordings (12-30 h) were reported separately, and remaining studies synthesized narratively (Part B) or longitudinally (Part C). Certainty was assessed using GRADE (PROSPERO CRD42026130103).

Twenty-eight studies (3232 participants; 9 cancer categories) were included; five met pooling criteria. Cancer patients showed lower SDNN (MD = -14.05 ms [95% CI -18.20, -9.90]), RMSSD (-16.76 ms [-21.23, -12.28]), and pNN50 (-6.05% [-9.36, -2.74]); all p < 0.001, I² = 22.1-33.7%. HF power was non-significant (p = 0.118). Leave-one-out analyses confirmed robustness, and within-cancer studies consistently showed inverse HRV-fatigue correlations. All pooled outcomes were Very Low certainty.

Cancer patients show consistently suppressed short-term time-domain HRV, a clinically plausible signal of autonomic impairment. Because it aggregates mechanistically distinct sources (malignancy, cardiotoxicity, perioperative vagal withdrawal, survivorship remodeling), the pooled estimate cannot attribute suppression to any cause, and Very Low certainty precludes recommending HRV as an established clinical biomarker. Treatment-phase-stratified studies with standardized protocols and non-linear indices are needed.

The hallmarks of cancer, first introduced by Hanahan and Weinberg in 2000 and updated in 2011 and in 2022, summarize the core processes that drive the stepwise development of tumors. This framework has proven highly effective for interpreting the vast complexity of cancer and its underlying biology. However, advances in spatially resolved single-cell technologies and more advanced imaging approaches have revealed additional layers of regulation that shape tumor behavior, particularly involving interactions between tumors and the nervous system. Although the influence of innervation on tumor cells and tumor vasculature has been widely studied, the impact of neurotransmitters, neural-derived factors, or neuropeptides on tumor-infiltrating immune cells remains largely unexplored and unexploited. Importantly, immune cells within the tumor microenvironment express receptors for various neural-derived signals, and can shift their phenotypes and adapt their functions in response to these inputs. Here, we highlight neuropeptide-driven pathways that modulate tumor-infiltrating immune cells to influence hallmark functions and, ultimately, shape tumor progression. Neural regulation of the tumor microenvironment is therefore emerging as a promising and potentially targetable layer that could complement existing cancer therapies.

SRSF3 (SRp20) is an essential RNA splicing factor. By conditional knockout (KO) of Srsf3, we found Srsf3 at its physiological level plays a tumor-suppressive role in mouse liver carcinogenesis. Srsf3 KO in hepatocytes disrupted sex disparity in the development of DEN-induced liver cancer and resulted in high incidence of liver cancer in both male and female mice. In contrast, Srsf3 is oncogenic in the mouse mammary glands and Srsf3 KO significantly delayed the development of Erbb2 breast cancer. Srsf3 KO significantly increased the expression of transcription factors Sox4, E2f1, and Myc, calcium channel factor Trpv4, and zinc-binding Trim6 in liver cancer, but did not in Erbb2 breast cancer. Srsf3 KO enhanced the expression of glucose transmembrane transporter Mfsd4a and translation initiator Eif4a2 in DEN-induced liver cancer but reduced Mfsd4a and Eif4a2 expression in breast cancer. More importantly, Srsf3 KO reduced the expression of hepatocyte ERα and transcription factor Foxa family genes essential for sexual dimorphism in liver cancer and their downstream targets leukemia inhibitory factor receptor Lifr and epidermal growth factor receptor Egfr, but increased the expression of Myc. We further evidenced that SRSF3 binds to FOXA1 promoter and is responsible for FOXA1 promoter activity and FOXA1 expression in liver cancer cells. Together, our data highlight a functional paradigm of SRSF3 at its physiological level in tissue context-dependent gene regulation and in facilitating hepatocyte ERα and FOXA1 expression for sex disparity in liver cancer development.

Pituitary adenomas constitute up to 20% of primary brain tumors, yet somatic mutations are only found in 15% of pituitary adenomas. Epigenomic dysregulation has been proposed as a tumorigenic mechanism in pituitary adenomas causing Cushing's disease (CD). We created paired datasets of human CD adenomas and en-route margin adult human pituitary glands, and assayed their chromatin accessibility, DNA methylation, transcriptomic, proteomic, and phospho-proteomic landscapes. In CD adenomas, we found epigenetic reactivation of a neurodevelopmental phosphoprotein program typically lost in the postnatal pituitary gland. CD cells overexpressed PPP1R17, an endogenous inhibitor of the protein phosphatase PP2A. Mechanistically, PPP1R17 overexpression in normal murine pituitary cells recapitulated the adenoma phenotype, and the resulting hyperproliferation was reversed in a PP2A-dependent manner by fingolimod, an FDA-approved small molecule, both in vitro and in vivo. Our findings highlight kinase-phosphatase imbalance as a targetable mechanism in CD.

Brain tumors are typically diagnosed after symptoms appear and requires definitive analysis of biopsy which takes a long time. Therefore, it is important to find markers for early diagnosis of different brain tumors. We aimed to validate and construct miRNA-based diagnostic panel for minimally-invasive differential diagnosis of brain tumors using plasma samples.

Circulating miRNAs were isolated from 67patients with glioblastoma, 33 with astrocytoma; 6 with oligodendroglioma; 33 with meningioma; 14 with lung cancer brain metastases and 25 with breast cancer brain metastases. Targeted and references miRNAs genetic expression was studied with RT-qPCR. Bioinformatics tools were used to develop diagnostic models and then functional enrichment for target genes and signalling pathways was conducted using KEGG, Reactome and WikiPathways databases.

Based on genetic expression of 10-miRNAs, validated models for differential diagnosis of each studied brain tumor were constructed. It was found that CASP3, EIF2S2, FYN, GNAQ, ITPR1, KPNB1, KREMEN1, MTOR, SREBF1, TYMS, VPS4B, and WASL were the most significant target genes of these miRNAs.

This study is among the first to include the three types of malignant brain tumors in addition to the benign brain tumor and also two types of secondary brain tumors. Results could be used as a minimally-invasive approach for early detection and monitoring recurrence of primary and metastatic brain lesions.