To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes.

To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and carries substantial morbidity. Metformin, a widely used antidiabetic agent, shows promise for HNSCC prevention, but resistance arises in a subset of tumors. In a recent issue of Cancer Prevention Research, Hoang and colleagues use CRISPR screening to identify key mediators of metformin resistance, including AMPK and protein kinase A (PKA), and demonstrate that the cyclooxygenase 2-prostaglandin E2 axis acts upstream of PKA. Because this pathway is readily inhibited by common nonsteroidal anti-inflammatory drugs (NSAID), the findings support clinical evaluation of combined metformin and NSAID therapy to improve HNSCC chemoprevention. See related article by Hoang et al., p. 79 .

Colorectal cancer incidence is rising globally among individuals younger than 50 years and remains poorly explained by established risk factors. In this study, we advance the hypothesis that early-childhood exposure to mutagen-producing bacteria contributes to lifetime colorectal cancer risk by imprinting oncogenic mutations in the developing colorectal epithelium, thereby initiating tumorigenesis decades before clinical diagnosis and redefining early-onset colorectal cancer as a disease rooted in early-life mutagenic exposure.

Increasing knowledge in molecular biology, enabled by multiomic technologies, data science, and global collaboration, extends cancer research beyond advanced disease settings toward earlier detection, interception, and more effective therapies. Through partnership, workforce development, and a commitment to equity and trust in science, discovery can be catalyzed into meaningful patient impact.

We propose a physics-based framework in which cancer cell state is defined by position and velocity in a continuous space of directly measurable physical variables-cell surface area (S) and volume (V)-and motion through S-V space as an interpretable proxy for plasticity. Therapy generates S-V vector fields that govern trajectories, enabling the design of drug combinations to steer heterogeneous cell populations toward nonviable states, offering a predictive and physically interpretable alternative to therapies directed against oncogenic mutations and/or predefined cell subpopulations.

Breast malignant phyllodes tumours are rare fibroepithelial neoplasms arising from periductal stromal cells, characterized by rapid progression and a high recurrence rate. The poor prognosis largely stems from the lack of effective therapeutic strategies, underscoring the insufficient understanding of their molecular mechanisms and therapeutic targets. Moreover, most previous studies have mainly focused on the tumour core, while the molecular features of the surrounding peritumoural tissue remain insufficiently explored.

Fusion protein AML1-ETO and chemokine receptor CXCR4 are crucial therapeutic targets for AML, the former plays a key role in differentiation blockade and leukemogenesis, and the latter is closely associated with drug resistance and relapse. This work developed a unified platform (referred as to E5-LNP@siAE) to integrate AML1-ETO-targeted RNA interference (RNAi) and CXCR4 antagonism by employing lipid nanoparticle (LNP) technology and antagonistic peptide E5 modification. The E5-LNP@siNC was slightly negative charged with 121.8 nm in diameter, showing homogenous spherical morphology and stability in PBS and 10% FBS. The E5-LNP@siAE could be specifically taken up by Kasumi-1 cells, down regulated levels of AML1-ETO, p-Erk and p-p38, and E5-LNP@siNC inhibited the CXCL12-mediated migration. In a refractory AML mouse model, E5-LNP@siAE monotherapy significantly reduced AML cells in peripheral blood, as well as infiltrations in the liver, lung and spleen. The expressions of CD11b, CD41a and Ter119 were upregulated while c-Kit decreased in the spleen of AML mice received E5-LNP@siAE treatment. The differentiation inductive effects were also observed in bone marrow mononuclear cells separated from AML patients with t(8;21) translocation. Moreover, E5-LNP@siAE significantly enhanced the therapeutic efficacy of doxorubicin (DOX) in the AML mice, evidenced by the reduced AML cells in peripheral blood, bone marrow and multiple organs, meanwhile, did not bring negative impacts on the counts of red blood cells and platelets. Consequently, the combination regimen achieved the much better result of survival prolongation than E5-LNP@siAE monotherapy, and the other control groups did not show therapeutic effects on the survival of the AML mice.

Distal cholangiocarcinoma (dCCA) is a malignant tumor characterized by a challenging diagnosis, high invasiveness, and extremely poor prognosis. Research on dCCA is limited by the scarcity of reliable patient-derived preclinical tumor models. This study established a novel human distal cholangiocarcinoma cell line, CBC3T-3, and systematically characterized its biological properties, genomic features, and potential for clinical application. This cell line was extracted from postoperative distal cholangiocarcinoma tumor from a 54-year-old male patient. It was stably passaged (> 50 generations) through primary culture and condition optimization, preserving the same pathology as that of the primary tumor. Whole-exome sequencing (WES) confirmed somatic mutations, tumor mutation burden, single-sample clonal structure, driver genes, and drug resistance genes in CBC3T-3 cells, revealing their genomic characteristics. Functional assays demonstrated that CBC3T-3 cells exhibit strong capabilities for proliferation, migration, and invasion in vitro. In a subcutaneous xenograft model in immunodeficient mice, palpable tumor nodules developed within 4 weeks, reflecting the clinical characteristics of rapidly progressive disease. Drug sensitivity analysis revealed that, compared with TFK-1 cells, CBC3T-3 cells presented significantly greater responses to paclitaxel, gemcitabine, and oxaliplatin but relatively poor responses to 5-FU and cisplatin. The integration of drug resistance gene findings from WES suggests that TP53 missense mutations may mediate primary resistance to cisplatin. The establishment of the CBC3T-3 cell line enhances the research toolkit for dCCA. Its genomic characteristics and functional plasticity provide a reliable preclinical tumor model for developing precision therapies and investigating drug resistance mechanisms.

A disintegrin and metalloprotease with thrombospondin type 1 repeats, 1 (ADAMTS1) is a metalloproteinase essential for ovarian follicle development and ovulation. It is also involved in organizing vascular and lymphatic networks within ovary. ADAMTS1 is expressed by granulosa cells in ovarian follicles, and its expression and function are regulated by gonadotropins, follicle-stimulating hormone, and luteinizing hormone. This enzyme cleaves extracellular matrix (ECM) proteins to remodel the ECM and provide the necessary space for the growing ovarian follicles. ADAMTS1 is also essential for breaking down the follicular wall by cleaving proteoglycans, thereby releasing oocytes during ovulation. Loss of ADAMTS1 impairs remodeling of the ECM and decreases ovulation in mice. Dysregulation of ADAMTS1 is also linked to pathological conditions like polycystic ovary syndrome and premature ovarian failure, highlighting the precise activity of this enzyme. This chapter discusses the known and potential functions of ADAMTS1 in ovarian biology.

Isocitrate dehydrogenase 1 (IDH1) mutations confer distinct biological properties to gliomas, including the reshaping of the tumor immune microenvironment. While T cell dysfunction in glioblastoma has been extensively characterized, the role of innate lymphoid cells (ILCs)-critical regulators of tissue homeostasis and early immune responses- remains poorly understood.

Resistance to 5-fluorouracil (5-FU) remains a major challenge in the treatment of colorectal cancer (CRC). Here, we identify ETS variant transcription factor 7 (ETV7) as significantly upregulated in CRC tissues and cell lines, with elevated expression associated with poor clinical prognosis. Functional assays demonstrate that ETV7 enhances CRC cell proliferation, invasion, and resistance to 5-FU. Mechanistically, ETV7 transcriptionally upregulates CXCL1, leading to increased neutrophil recruitment and enhanced formation of neutrophil extracellular traps (NETs). The resulting NETs-enriched tumor microenvironment promotes tumor aggressiveness and chemoresistance. Pharmacological inhibition of CXCL1 or degradation of NETs effectively attenuates ETV7-driven malignant phenotypes in vitro and in vivo. Collectively, these findings establish an ETV7-CXCL1-NETs axis that contributes to 5-FU resistance in CRC and suggest that targeting this pathway may improve chemotherapy response.

Although targeted therapy has made significant advances in cancer treatment throughout these years, drug resistance still remains a major obstacle. Plenty of evidence has proved that abnormal expression of receptor tyrosine kinase AXL is associated with targeted therapy resistance and poor clinical outcomes. AXL drives drug resistance through diverse mechanisms, including altering tumor cell phenotypes, orchestrating DNA damage response process, promoting the activation of bypass signals, or interacting with other receptor tyrosine kinases. Preclinical and clinical studies have demonstrated that combined inhibition of AXL and the other target can enhance the efficacy of various targeted therapies and improve outcomes for patients with drug resistance. This review summarizes recent advances in the specific roles of AXL in targeted therapy resistance and AXL-targeted treatment strategies. It further explores the potential clinical value of combinatorial approaches involving AXL inhibition and discusses future directions for its application in developing novel targeted therapies and advancing precision oncology treatment. 
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Metabolic reprogramming is a hallmark of cancer, with the Warburg effect-driven aerobic glycolysis leading to a substantial accumulation of lactate in the tumor microenvironment. For a long time, lactate was considered a mere metabolic end product; however, recent studies have found that it acts as an important signaling molecule, profoundly influencing tumor progression by inducing a novel post-translational modification - lactylation. Lactylation, driven by lactate, occurs on both histones and non-histone proteins and is finely regulated by the 'writer' 'eraser' and 'reader' mechanisms, thereby altering the function of target proteins and gene expression. This review systematically explores the bidirectional regulatory network between glycolytic reprogramming and lactylation: on one hand, key glycolytic regulators promote lactate production, thereby increasing lactylation levels; on the other hand, lactylation can feedback to regulate the activity and expression of key glycolytic enzymes, forming a pro-tumor positive feedback loop. This interaction plays a central role in tumor proliferation, metastasis, DNA damage repair, and immune evasion. Consequently, targeting lactate production, lactate transport, or the lactylation process itself has emerged as a highly promising anti-cancer strategy and shows potential synergy with existing therapies such as immune checkpoint inhibitors. In-depth analysis of the glycolysis-lactylation axis will provide a crucial theoretical basis for developing novel cancer treatment approaches.
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First-line immunotherapy for advanced non-small cell lung cancer (NSCLC) shows significant survival benefits in patients without driver mutations, but the optimal duration of treatment remains controversial. Some studies support limiting immunotherapy to 2 years, arguing that longer treatment does not bring additional survival benefits; while other studies believe that treatment should continue until disease progression to maximize survival benefits. This article systematically reviews the current research progress on the duration of immunotherapy and discusses the potential predictive value of biomarkers such as circulating tumor DNA (ctDNA), the best efficacy response, and programmed cell death ligand 1 (PD-L1) expression levels in individualized treatment decisions. More prospective studies, especially biomarker-driven trials, are still needed to clarify the optimal duration of treatment and establish an individualized treatment strategy based on multidimensional indicators.
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Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide, and its occurrence and development are closely related to complex molecular mechanisms. Alternative splicing of precursor mRNA is a key step in gene expression regulation, and its dysregulation is common in tumors. The serine/arginine-rich splicing factor (SRSF) family, a core protein family in splicing regulation, has been confirmed to play oncogenic roles in various cancers. However, systematic research on the SRSF family in NSCLC remains insufficient. This study aims to systematically analyze the specific expression patterns, clinical prognostic value, collaborative mechanisms and potential biological functions of SRSF individual members in NSCLC by the combination of bioinformatics analysis and experimental verification.

The prognosis for non-small cell lung cancer (NSCLC) with leptomeningeal metastasis (LM) is extremely poor. However, in oncogene addicted patients, the emergence of targeted therapies with high central nervous system (CNS) penetration is significantly reshaping the treatment landscape. Existing guidelines, which often favor conservative strategies, are no longer sufficient to meet the demands of precision medicine. To address this challenge, the Metastasis Lung Cancer Collaboration Group, Youth Specialists Committee of Beijing Medical Reward Foundation convened multidisciplinary experts from Medical Oncology, Radiology, Pathology, Radiotherapy, and Neurosurgery. Based on evidence-based medicine from the past decade and clinical practice experience, they have developed the Chinese expert consensus on clinical management of oncogene addicted NSCLC with leptomeningeal metastasis (2026 edition). This consensus emphasizes that the diagnosis of LM should be based on a comprehensive assessment of clinical symptoms, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) cytology. It also highlights the critical role of CSF molecular liquid biopsy in clarifying driver gene status and assessing treatment efficacy. In terms of treatment, this consensus advocates for a fundamental paradigm shift: therapy should be led by a multidisciplinary team (MDT), with high-CNS-penetration targeted therapies as the first-line intervention, while local treatments (such as intrathecal injection and radiotherapy) are positioned as supplementary measures. The consensus provides a series of expert recommendations on key aspects, including the selection of high-CNS-penetration tyrosine kinase inhibitors (TKIs), the application of intrathecal chemotherapy, the timing of radiotherapy, and palliative surgery. It aims to establish proactive, individualized treatment standards for patients with NSCLC LM in China, based on molecular subtyping and MDT collaboration, thereby improving patient survival outcomes.
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Tumor mutational burden (TMB) and PD-L1 are established biomarkers for guiding immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC). As ICI use expands into early-stage disease, we explored the feasibility of using TMB, which can be determined via a comprehensive genomic profiling assay along with EGFR and ALK genomic alterations, as a biomarker for outcomes in both neoadjuvant and adjuvant settings. TMB-high status (≥10 mut/Mb) showed a numerically higher, but not statistically significant, rate of pathological complete response among patients receiving neoadjuvant ICI and significantly associated with more favorable time to recurrence in patients receiving adjuvant ICI, particularly among patients with PD-L1 expression <50%. TMB should be considered in future early-stage NSCLC ICI clinical trials to further validate these results.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The higher incidence and earlier onset of HCC in sub-Saharan Africa suggest a potential role for a genetic predisposition. This study evaluated the association of TERT-rs2242652-(A), a variant linked to lower HCC risk, with HCC in populations from Ghana, Nigeria, and Cameroon, compared with a population from the United States.

Gliomas exhibit significant prognostic heterogeneity, and single-omics data/existing technologies struggle to balance multi-omics integration efficiency, prediction accuracy, and clinical adaptability-hindering the clinical translation of precise prognostic assessment. Focussing on glioblastoma (GBM) and lower-grade glioma (LGG), this study proposes an integrated solution: three-step multi-omics feature selection combined with the limited random forest (FRF) model, using TCGA-derived transcriptomic, genomic, epigenomic and clinical survival data. Prognosis-related features are first screened using univariate Cox regression, refined by random forest-based feature importance for dimensionality reduction and then integrated into a multi-omics matrix through sample matching. The FRF model balances efficiency and accuracy by limiting decision tree number and depth, optimising node splitting criteria, and adding a dual-weighted correction mechanism. Results show that FRF achieves an AUC of 0.96 for GBM, outperforms logistic regression (LR) and support vector machine (SVM) across all LGG metrics, and reduces training time to minutes-meeting the 2-h clinical prognostic demand. Ablation experiments confirm that the multi-omics model improves performance by 11.63% compared with the optimal single-omics model, with core features consistent with glioma molecular mechanisms. This resolves the challenge of rapid integration and precise prediction, providing an efficient tool for glioma prognostic assessment and supporting multi-omics clinical translation.