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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To investigate the clinical characteristics and prognosis of childhood acute lymphoblastic leukemia (ALL) with PDGFRB rearrangement.

Clinical data from five patients with refractory/relapsed acute myeloid leukemia (AML) and RUNX1::RUNX1T1 fusion gene, treated with venetoclax, cytarabine, and homoharringtonine-based cytoreductive therapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT) at Ruijin Hospital between March 2023 and December 2024, were retrospectively reviewed. The median time from diagnosis to allo-HSCT was 315 days (range: 217-560) . All patients achieved full donor chimerism by day 30 post-allo-HSCT. Within 6 months after transplant, the RUNX1::RUNX1T1 fusion gene was undetectable in all patients, with a median time to negative conversion of 2 months (range: 1-6 months) . The median follow-up time was 625 days (range: 372-1 010) . All patients remained disease-free, with no events of measurable residual disease (MRD) positivity by flow cytometry or molecular analysis documented. These findings preliminarily confirm that venetoclax, cytarabine, and homoharringtonine-based cytoreductive therapy is a safe and effective bridging therapy for allo-HSCT in patients with refractory/relapsed AML and RUNX1::RUNX1T1 fusion gene.

Objective: To analyze the clinical characteristics, therapeutic regimens, and prognosis of double-hit multiple myeloma (DHMM) patients with concurrent 1q21 copy number gain (1q21+) and t (4;14) , and to explore effective strategies to improve outcomes of this high-risk subgroup. Methods: A retrospective analysis was performed on 96 newly diagnosed DHMM patients with both 1q21+ and t (4;14) admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from September 2014 to September 2024. Baseline clinical characteristics, prognosis, and independent prognostic factors were evaluated. A logistic regression model was used to analyze the correlation between induction regimens, autologous hematopoietic stem cell transplantation (auto-HSCT) , and minimal residual disease (MRD) negativity. Results: The median age of the 96 DHMM patients was 62 (range: 36-79) years. Among them, 50 cases (52% ) were at R2-ISS stage Ⅳ, 11 cases (11% ) had concurrent del (17p) , 35 cases (36% ) underwent auto-HSCT, 39 cases (41% ) received triple-agent induction therapy with proteasome inhibitor (PI) , immunomodulatory drug (IMiD) and anti-CD38 monoclonal antibody (CD38Ab) , 25 cases (26% ) achieved MRD-negative complete response (CR) . The clone size of 1q21+ was positively correlated with that of t (4;14) (r=0.46, P<0.001) , while the clonal burden of 1q21+ was significantly lower than that of t (4;14) . With a median follow-up of 36 (range: 6-126) months, the median progression-free survival (PFS) was 26 (95% CI: 22-50) months, and the estimated median overall survival (OS) was 4.3 (95% CI: 2.1-6.4) years. Extramedullary relapse occurred in 22 cases (23% ) . Multivariate analysis showed that newly diagnosed extramedullary involvement of soft tissue was an independent risk factor for both PFS and OS (all P<0.05) . Del (17p) shortened PFS, whereas MRD negativity significantly prolonged PFS. Both triple-agent induction therapy (PI+IMiD+CD38Ab) and auto-HSCT improved the MRD-negative rate (all P<0.05) . Conclusion: DHMM patients with concurrent 1q21+ and t (4;14) exhibit aggressive clinical features and poor prognosis. Triple-agent induction therapy (PI+IMiD+CD38Ab) and auto-HSCT are associated with MRD negativity and improved PFS, but achieving long-term survival remains challenging for these patients.

mRNA-targeted tumor drugs, featuring various types and distinct antitumor mechanisms of action, have demonstrated significant potential in tumor immunotherapy. Currently, nearly one hundred registered clinical trials initiated by pharmaceutical companies or sponsors are being conducted worldwide, and these trials have shown impressive efficacy. In China, multiple registered clinical trials have been conducted in the past two years, reflecting rapid development. Although mRNA tumor drugs still face certain challenges, the advantages of mRNA technology are clear, promoting the integrated development of immunotherapy, gene therapy, and cell therapy. With ongoing technological innovation and optimization, the demand for "mRNA therapy" for tumor prevention and treatment is expected to be met. This review discusses the distinct mechanisms of action, progress in basic research, clinical advancements, challenges, and future perspectives of both prophylactic and therapeutic mRNA cancer vaccines. It aims to enhance understanding of research progress in mRNA technology for oncological drug applications and to provide insights for future research and product development of mRNA-based interventions in oncology.

To develop a machine-learning model that integrates routine clinical parameters with tumor mutational burden (TMB) and to evaluate its performance in predicting responses to programmed death-1 (PD-1)/programmed death-ligand 1(PD-L1) inhibitors across various cancer types.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare and highly aggressive mesenchymal neoplasm that is frequently associated with anaplastic lymphoma kinase (ALK) gene fusion. Surgical resection remains the cornerstone of treatment for patients with early- and intermediate-stage EIMS; however, a standardized therapeutic approach for advanced-stage EIMS has yet to be established. Primary pulmonary EIMS is exceedingly rare, with only a limited number of cases reported in the literature. While treatment with ALK-tyrosine kinase inhibitors (TKIs) is considered a viable therapeutic option, and clinical outcomes with monotherapy using ALK-TKIs have frequently been suboptimal. This study presents a case of advanced primary pulmonary EIMS with a TPM3-ALK fusion. The patient received first-line targeted therapy with the second-generation ALK-TKI Ensartinib, in conjunction with radiotherapy for residual and metastatic lesions. This treatment regimen resulted in significant tumor reduction and sustained disease control. The progression-free survival (PFS) exceeded 32 months, with no significant treatment-related adverse events observed. This study investigates the feasibility of combining targeted therapy with local radiotherapy, guided by genetic testing, to offer novel treatment strategies for patients with advanced primary pulmonary EIMS.
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Cancer treatment is a significant challenge facing global medicine, with complex molecular mechanisms and drug resistance being key factors limiting treatment outcomes. Abnormal lipid metabolism is one of the important characteristics of tumors, providing metabolic support for the growth, proliferation, migration, and invasion of tumor cells. Tumor suppressor p53 protein and sterol O-acyltransferase 1 (SOAT1) play an important role in regulating cellular lipid metabolism and are closely related to the occurrence, development, and prognosis of various tumors. p53 protein regulates tumor lipid metabolism through multiple signaling pathways, while SOAT1, as a key enzyme in cholesterol esterification, is highly expressed in many tumors and accelerates tumor progression. Recent studies have shown that there may be a functional association between p53 protein and SOAT1, coordinating the regulation of lipid homeostasis in tumor cells. This article reviews the research progress on p53 protein and SOAT1 in tumor lipid metabolism, focusing on the potential mechanisms of action of the p53-SOAT1 axis in tumor development, and prospects its application prospects as a target for cancer treatment.
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Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC), and epidermal growth factor receptor (EGFR) mutation is its primary molecular driver event. Although the third-generation tyrosine kinase inhibitors (TKIs) Osimertinib has become the standard first-line therapy for such patients, the development of drug resistance severely limits long-term survival benefits. However, increasing evidence suggests that epigenetic remodeling is a crucial non-genetic mechanism contributing to resistance. Specifically, hypermethylation of DNA promoter regions can assist tumor cells in evading drug cytotoxicity by silencing key tumor suppressor genes or metabolic regulatory genes. This study aims to identify key genes regulating Osimertinib sensitivity through machine learning and high-throughput screening, and to dissect the role of methylation modifications in regulating primary resistance to Osimertinib.

Leptomeningeal metastasis (LM) is a devastating complication of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), with a poor prognosis. While high-dose third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can enhance drug concentrations in the central nervous system, their efficacy as monotherapy remains limited. Intrathecal Pemetrexed (IP) offers a promising local treatment approach by bypassing the blood-brain barrier and acting directly within the cerebrospinal fluid. However, clinical data on the efficacy and safety of combining high-dose third-generation EGFR-TKIs Furmonertinib (160 mg/d) with IP in EGFR-mutant NSCLC-LM patients are still scarce. Therefore, this study aims to evaluate the efficacy and safety of this combination regimen in this population to provide real-world data support for clinical practice.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a newly defined type of epithelial tumor in the 2021 World Health Organization (WHO) fifth edition classification of thoracic tumors, with a low incidence. Currently, its treatment and prognosis remain unclear. Pathologically, it can be distinguished from SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) based on histological morphology and immunohistochemistry, yet whether there are differences in their clinical features, sensitivity to radiotherapy, and prognosis remains unknown. This study aimed to analyze the clinical characteristics of patients with SMARCA4-UT and SMARCA4-dNSCLC and to identify prognostic factors.

To evaluate the associations of serum methotrexate (MTX) concentrations and MTHFR gene polymorphisms with delayed metabolism of high-dose MTX and adverse reactions in children with acute lymphoblastic leukemia (ALL).

Ultraviolet (UV) radiation, one of the critical environmental carcinogenic factors, promotes skin photoaging and carcinogenesis by inducing DNA damage, oxidative stress, and chronic inflammatory cascades. N6-methyladenosine (m6A)-modifying enzymes (writers, erasers, and readers) play bidirectional regulatory roles in UV-mediated skin pathology. In photoaging, the reactive oxygen species (ROS)-m6A axis accelerates collagen degradation and epithelial-mesenchymal transition (EMT) through modulation of matrix metalloproteinases (MMPs), inflammatory mediators, DNA damage repair, apoptosis, and collagen metabolism. In skin cancers, m6A regulators promote tumor progression by influencing oncogenic signaling, proliferation, invasion, metastasis, and immune evasion. Bioactive monomeric compounds derived from traditional Chinese medicine, including polyphenols, saponins, and alkaloids, can regulate the activity of m6A enzymes to interfere with photoaging and UV-induced skin carcinogenesis. This study integrates current evidence to establish an m6A-targeted epigenetic intervention framework for UV-induced skin injury and highlights the potential of synergistic multi-component m6A-modulating therapeutic strategies as a future research priority.

Given the high incidence, poor prognosis, and scarcity of high-quality multimodal research data for acral melanoma in the Chinese population, this study aims to build a representative multimodal disease-specific cohort to provide a high-quality data foundation for characterizing disease features and exploring mechanisms of prognosis.

The occurrence, metastasis, and drug resistance of melanoma pose major challenges to patient prognosis, and predictive models capable of accurately forecasting patient outcomes and guiding treatment are still lacking. This study aims to develop predictive models for melanoma prognosis and drug sensitivity based on mechanisms of programmed cell death (PCD).

Breast cancer is one of the most common malignant tumors in women worldwide, and its high incidence and mortality rate seriously threaten women's health. Studies show that the forkhead box O3a (FoxO3a) plays a key role in the occurrence and progression of breast cancer, particularly in the regulation of apoptosis. As a major member of the FoxO family, FoxO3a exerts tumor-suppressive functions by participating in apoptosis regulation and cell-cycle control. In breast cancer cells, FoxO3a acts as a downstream signaling hub of multiple upstream pathways including phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), mitogen-activated protein kinase (MAPK), and serum- and glucocorticoid-regulated kinase 1 (SGK1). Through nucleocytoplasmic shuttling and alterations in transcriptional activity, FoxO3a precisely modulates the expression of apoptosis-related target genes such as Bcl-2-interacting mediator of cell death (Bim) and p53-upregulated modulator of apoptosis (PUMA), thereby influencing cell survival or death. In addition, multiple natural compounds and combination therapies can induce apoptosis in breast cancer cells by restoring or enhancing FoxO3a activity, and may partially overcome treatment resistance. Systematic elucidation of the complexity of the FoxO3a signaling network and its dual roles in breast cancer therapy may provide theoretical support for understanding tumor-drug resistance mechanisms and for developing precision therapeutic strategies targeting FoxO3a nodes. Future research should further clarify the functional differences among FoxO3a splice variants and FoxO family members, reveal the molecular basis of FoxO3a functional switching in the tumor microenvironment, and promote the clinical translation of biomarkers and targeted drugs.