Oncology Research最新文献

{"title":"Gastric Cancer-Derived Exosomes Activate Mast Cells via the SCF/c-KIT Pathway to Drive Angiogenesis and Metastasis.","authors":"Shaoxiong Bai, Yilei Duan, Tian Yao, Yanan Shi, Xin Zhang, Xiaole Ma, Kai Jia","doi":"10.32604/or.2026.085030","DOIUrl":"10.32604/or.2026.085030","url":null,"abstract":"<p><p><b>Background:</b> Exosomes mediate intercellular communication within the tumor microenvironment. However, their role in modulating mast cell activity in gastric cancer (GC) remains unclear. This study aimed to elucidate whether GC-derived exosomes activate mast cells via the SCF/c-KIT pathway to promote angiogenesis and metastasis, and to assess the therapeutic potential of targeting this axis. <b>Methods:</b> Exosomes were isolated from GC cell lines (AGS, MKN1), a normal gastric epithelial cell line (GES-1), and mouse gastric tumor tissues, followed by characterization via NTA, TEM, and western blot. Mast cell (LAD2) degranulation was quantified by β-hexosaminidase release and ELISA. Cell recruitment was evaluated using Transwell migration assays, and angiogenesis was assessed by tube formation assay. Underlying signaling pathways were analyzed by Western blot. The functional role of the SCF/c-KIT axis was investigated using shRNA-mediated knockdown and neutralizing antibodies. A mouse model of gastric cancer lung metastasis was established to validate the <i>in vivo</i> effects. <b>Results:</b> GC-derived exosomes, but not GES-1-derived ones, were enriched with SCF and induced mast cell recruitment, degranulation, and tryptase release via SCF/c-KIT activation. Mast cell-derived tryptase promoted angiogenesis by activating the MAPK pathway and upregulating VEGF in endothelial cells. <i>In vivo</i>, tumor-derived exosomes accelerated lung metastasis and angiogenesis, effects abrogated by a c-KIT blocking antibody, confirming SCF/c-KIT dependence. <b>Conclusion:</b> Gastric cancer-derived exosomes deliver SCF to activate mast cells via the c-KIT receptor, thereby fostering angiogenesis and metastasis. Targeting the exosomal SCF/c-KIT signaling axis may offer a promising therapeutic strategy to impede gastric cancer progression.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"27"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged Disease Stability with Durvalumab and Tremelimumab Rechallenge Following Prior Immune Checkpoint Inhibitors: A Case Report.","authors":"Waseem Abdelrahim, Ebtesam Al-Najjar, Seif El Beheary, Abdullah Esmail","doi":"10.32604/or.2026.083193","DOIUrl":"10.32604/or.2026.083193","url":null,"abstract":"<p><p><b>Background:</b> Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a leading cause of cancer-related mortality worldwide due to frequent recurrence and early metastasis. While immune checkpoint inhibitor (ICPI)-based regimens have revolutionized the treatment landscape for advanced HCC, clinical evidence regarding the safety and efficacy of ICPI rechallenge following disease progression or severe immune-related adverse events (irAEs) remains sparse. This report describes a case of prolonged disease stability achieved through sequential immunotherapy using durvalumab and tremelimumab (Durva/Treme) after prior ICPI failure and high-grade toxicity. Case Description: A 65-year-old male with recurrent stage IV HCC and metastases to the adrenal glands and vertebral column was referred to our center after failing multiple lines of therapy, including atezolizumab/bevacizumab, sorafenib, and cabozantinib. Subsequent treatment with nivolumab plus ipilimumab was complicated by grade 3/4 immune-related hepatitis, necessitating a treatment hold and steroid intervention. Despite an initial response in hepatic lesions, imaging confirmed progression in the adrenal metastases. The patient was then transitioned to a rechallenge protocol with the STRIDE regimen (Durva/Treme). The patient completed 39 cycles of therapy over more than three years. Serial imaging demonstrated sustained stable disease (SD), and a significant reduction in alpha-fetoprotein (AFP) levels initially declined substantially during nivolumab/ipilimumab (Nivo/Ipi) therapy, rebounded prior to Durva/Treme initiation, and subsequently stabilized near baseline levels during ongoing Durva/Treme treatment. Notably, the rechallenge was well-tolerated with no recurrence of high-grade hepatotoxicity. <b>Conclusions:</b> This case demonstrates that ICPI rechallenge with Durva/Treme may provide durable disease control in selected patients with advanced HCC, even those with a history of severe immune-related toxicity. While the localized response was likely augmented by interval radiotherapy, the overall clinical course suggests that the STRIDE regimen may offer a feasible sequential immunotherapy option. These findings warrant further prospective investigation into the biological mechanisms of immune re-priming and the safety of immunotherapy sequencing in advanced oncology.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"28"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Non-Invasive Blood Markers for Intraductal Papillary Mucinous Neoplasm Grading.","authors":"Liang Chen, Yitong Yuchi, Qian Zhu","doi":"10.32604/or.2026.084411","DOIUrl":"10.32604/or.2026.084411","url":null,"abstract":"<p><p>Intraductal Papillary Mucinous Neoplasm (IPMN) is a major precancerous lesion of pancreatic ductal adenocarcinoma. Accurate risk stratification of IPMN is key to preventing and controlling pancreatic cancer. At present, clinicians mainly grade IPMN following the Kyoto consensus guidelines, together with imaging examinations and traditional serum biomarkers like CA19-9 and CEA. This review unveils the latest research progress of non-invasive blood biomarkers for the grading of IPMN, including the diagnostic performance, molecular mechanisms, and current clinical translation of several types of markers. ApoAII has already been applied in clinical practice, and miRNA combinations, circulating cell-free DNA (cfDNA) methylation panels, and other markers show excellent value in IPMN stratification. However, the field still faces bottlenecks in clinical translation. In the future, researchers should focus on exploring specific targets for IPMN malignant transformation, unifying detection standards, and building multi-dimensional combined evaluation models. These efforts will help promote the application of non-invasive blood biomarkers in accurate IPMN grading and support the early screening and treatment of pancreatic cancer. It not only enables doctors to comprehensively understand the research status of existing non-invasive blood markers for IPMN, but also provides guidance for exploring promising non-invasive biomarkers in future studies.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"10"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Metabolic States in TNBC: Orchestrating Spatiotemporal Adaptation and Therapy.","authors":"Yida Wang, Haiyue You, Jingyi Gao, Feng Zhang, Xin Ning, Xinfeng Yang, Zhiwen Qian, Ying Jiang, Lu Liu, Danping Wu, Yanfang Gu, Daozhen Chen, Yan Zhang","doi":"10.32604/or.2026.085967","DOIUrl":"10.32604/or.2026.085967","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is characterized by marked metabolic plasticity, spatial heterogeneity, and therapy-induced adaptive remodeling. However, TNBC metabolism is often discussed as isolated pathways, making it difficult to link metabolic rewiring to immune exclusion, drug-tolerant persister cells, and treatment windows. Here, we propose a functional metabolic operating-state framework to organize recurrent adaptive programs in TNBC. Importantly, the S1-S5 framework is not a clinically validated subtype classification, but a set of coexisting and reversible operating states shaped by microenvironmental and therapeutic pressures. S1 represents a glycolysis-lactate/acidosis barrier; S2 denotes fatty acid oxidation (FAO)/oxidative phosphorylation (OXPHOS)-supported persister-like survival; S3 reflects NADPH and one-carbon metabolism-mediated reductive defense; S4 captures lipogenesis, cholesterol metabolism, and membrane remodeling; and S5 represents a ferroptosis tipping window emerging when redox and lipid-peroxide defenses fail. We further highlight flux-valve nodes that redirect carbon, nitrogen, lipid, and redox allocation, thereby biasing transitions among these states. Integrating evidence from spatial omics, metabolic imaging, tumor immunology, and therapeutic studies, we discuss how metabolic isozones reinforce immune suppression and how staged interventions may exploit state-specific vulnerabilities. This framework is intended to generate monitorable and falsifiable decision hypotheses for biomarker development, combination therapy design, and future prospective validation in TNBC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"13"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenoid Cystic Carcinoma of the Breast: Clinicopathological Features and Long-Term Outcomes from a 20-Year Retrospective Cohort.","authors":"Iseult M Browne, Susanna Slater, Myrto Kastrisiou, Mae Alghawas, Edward Phillips, Mark Beresford, Stephen R D Johnston, Zoe Kemp, Emma Kipps, Marina Parton, Nicholas C Turner, Alicia F C Okines","doi":"10.32604/or.2026.085356","DOIUrl":"10.32604/or.2026.085356","url":null,"abstract":"<p><strong>Background: </strong>Adenoid cystic carcinoma (ACC) of the breast is a rare triple-negative malignancy with an indolent clinical course distinct from conventional triple-negative breast cancer (TNBC). Optimal management remains undefined due to limited prospective data. This study aimed to characterise the clinicopathological features, treatment patterns, and long-term outcomes of breast ACC at a high-volume specialist centre, contributing real-world evidence to inform management in the absence of prospective trial data.</p><p><strong>Methods: </strong>A single-institution retrospective cohort study was conducted of 24 patients with histopathologically confirmed breast ACC treated at The Royal Marsden NHS Foundation Trust between 2000 and 2020. Clinicopathological and outcome data were analysed descriptively; overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) were estimated using the Kaplan-Meier method.</p><p><strong>Results: </strong>Median age was 57 years. Nodal involvement was rare (8%). Adjuvant radiotherapy was administered in 88% of patients; only two patients (8%) received chemotherapy for breast ACC. Five patients (21%) experienced disease relapse after a median of 2.3 years (range 1.3-14.0). The estimated 5- and 10-year OS were both 88.4% (95% CI 74.5-100%) and DSS were both 93.3% (95% CI 81.5-100%).</p><p><strong>Conclusions: </strong>To our knowledge this represents the largest single-institution cohort study of breast ACC reported to date. The clinical behaviour of breast ACC more closely resembles salivary gland ACC than conventional TNBC, supporting a conservative locoregionally focused management approach and questioning the routine use of chemotherapy on the basis of triple-negative receptor status alone. The propensity for late relapse supports long-term surveillance beyond the standard 5-year window.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"20"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Dysfunction in Renal Cell Carcinoma: A Comprehensive Review of Pathogenic Mechanisms and Emerging Therapeutic Opportunities.","authors":"Yanhong Wang, Junbo Liu, Qiaoping Xu, Zhao Ma","doi":"10.32604/or.2026.082432","DOIUrl":"10.32604/or.2026.082432","url":null,"abstract":"<p><p>In renal cell carcinoma (RCC), alterations in cellular metabolism are a defining feature, among which impaired mitochondrial function stands out as a key factor influencing both tumor aggressiveness and patient responses to therapy. The aim of this review is to systematically synthesize current knowledge on the role of mitochondrial dysfunction in RCC pathogenesis and to explore emerging therapeutic strategies targeting mitochondrial vulnerabilities. This comprehensive analysis examines the integrated dysregulation of core mitochondrial processes-bioenergetic metabolism, organelle dynamics, programmed cell death pathways, redox homeostasis, and selective autophagy-in driving RCC pathogenesis. Our synthesis reveals how genetic drivers, molecular regulators, and microenvironmental cues converge to remodel mitochondrial function, creating both adaptive advantages and therapeutic vulnerabilities. A paradoxical duality emerges in mitochondrial biology: processes such as fission, mitophagy, and reactive oxygen species (ROS) generation can simultaneously support tumor adaptation while rendering cells susceptible to targeted interventions. We evaluate emerging therapeutic approaches directed at mitochondrial vulnerabilities, including metabolic inhibitors, nanoscale delivery systems, and phytochemical agents, while addressing current limitations in specificity and resistance mechanisms. Based on current preclinical evidence, this integrated perspective establishes mitochondrial dysfunction as a central determinant of RCC malignancy and suggests potential combinatorial strategies for precision oncology approaches that warrant further investigation.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"14"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Immunotherapy for Cervical Cancer: Next Therapeutics Frontiers.","authors":"Danning Zhao, Qin Liu","doi":"10.32604/or.2026.084736","DOIUrl":"10.32604/or.2026.084736","url":null,"abstract":"<p><p>Cervical cancer, particularly its advanced stages, requires novel therapeutic paradigms. Cellular immunotherapy exploits the constitutive expression of HPV E6/E7 oncoproteins as near-ideal tumor-specific antigens. This review systematically evaluates four principal platforms under investigation: tumor-infiltrating lymphocytes (TILs), TCR-engineered T cells, CAR-T cells, and CAR-NK cells. We critically analyze the preclinical rationale, clinical trial landscape, safety considerations, and manufacturing challenges for each modality. TIL therapy has achieved durable complete responses and an FDA Breakthrough Therapy designation. TCR-T cells enable precise targeting of intracellular viral epitopes but are HLA-restricted. CAR-T cells offer potent, MHC-independent recognition, yet face on-target/off-tumor toxicity and a suppressive tumor microenvironment. CAR-NK cells present a favorable safety profile and off-the-shelf potential. We conclude that the future of this field lies in rational combination strategies (e.g., with immune checkpoint blockade) and next-generation engineering (e.g., armored CARs, logic gates, allogeneic platforms) to overcome manufacturing complexity, toxicity, and high costs. Overcoming these barriers is essential to extend these therapies to resource-limited settings where the burden of cervical cancer is highest.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"9"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase II Clinical Trial of Chemotherapy Rechallenge with or without Targeted Therapy in Refractory Metastatic Colorectal Cancer.","authors":"Chenchen Wang, Mingzhu Huang, Wenhua Li, Xuedan Sheng, Xiaoying Zhao, Xiaodong Zhu, Zhiyu Chen, Zhe Zhang, Haiming Li, Weijian Guo","doi":"10.32604/or.2026.084378","DOIUrl":"10.32604/or.2026.084378","url":null,"abstract":"<p><p><b>Background:</b> Patients with refractory metastatic colorectal cancer (mCRC) face limited treatment options after failure of standard therapies. This single-arm, phase II study aimed to evaluate the efficacy and safety of rechallenge strategies using previously effective regimens in late-line mCRC. <b>Methods</b>: Patients who progressed after ≥2 lines of prior chemotherapy, with a prior progression-free survival (PFS) ≥4 months and a ≥4-month treatment-free interval on that regimen were enrolled. Patients received rechallenge chemotherapy (oxaliplatin-, irinotecan-, or raltitrexed-based) with or without targeted agents (bevacizumab or cetuximab). Primary endpoint was investigator-assessed PFS. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. <b>Results</b>: Forty-three patients were enrolled (31 received chemotherapy plus targeted agents; 12 received chemotherapy alone). One patient discontinued treatment, leaving 42 patients evaluable for tumor response. The median PFS and OS were 3.97 months (95% CI: 2.46-5.48) and 13.03 months (95% CI: 9.68-16.38), respectively, while the ORR and DCR were 2.4% and 61.9%. Subgroup analysis showed that patients receiving chemotherapy plus targeted agents had higher DCRs (80.0% for bevacizumab-based regimens and 72.7% for cetuximab-based regimens vs. 18.2% for chemotherapy alone;) and longer median PFS (4.17 and 4.50 months vs. 1.57 months, respectively). Grade 3 or 4 adverse events were reported in 39.5% of patients, with no severe adverse events or treatment-related deaths observed. <b>Conclusion</b>: Chemotherapy rechallenge strategies, particularly when combined with targeted agents, demonstrated promising clinical activity and acceptable safety in selected heavily pretreated patients with mCRC who previously achieved sustained disease control.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"25"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-152-3p Overcomes Temozolomide Resistance in Glioblastoma by Targeting TGF-α and Enhancing Apoptosis.","authors":"Chun-Nun Chao, Chiung-Yao Fang, Chia-Hsin Hou, Jen-Tsung Yang, Yu-Ping Wu, Jui-Chieh Chen","doi":"10.32604/or.2026.083962","DOIUrl":"10.32604/or.2026.083962","url":null,"abstract":"<p><p><b>Objectives:</b> Temozolomide (TMZ) resistance remains a major challenge in glioblastoma (GBM) treatment. This study investigated the role of miR-152-3p and its downstream target, transforming growth factor-α (TGF-α), in regulating TMZ sensitivity in GBM. <b>Methods:</b> Public GEO and CGGA datasets were analyzed to evaluate the expression and prognostic significance of miR-152-3p. TMZ-resistant GBM cell lines (U87MGR and DBTRG-05MGR) were established by continuous TMZ exposure. Gain- and loss-of-function experiments were performed using miR-152-3p mimics and inhibitors. Cell viability, apoptosis, and TGF-α expression were assessed by MTT, qRT-PCR, and Western blot analyses. <b>Results:</b> miR-152-3p expression was significantly decreased in recurrent GBM and was associated with poor overall survival. TMZ-resistant GBM cells exhibited lower miR-152-3p expression than parental cells. Bioinformatic analyses identified TGF-α as a potential target of miR-152-3p. Overexpression of miR-152-3p suppressed TGF-α expression, reduced cell viability, and enhanced TMZ-induced apoptosis in resistant GBM cells. TGF-α knockdown similarly restored TMZ sensitivity. Conversely, inhibition of miR-152-3p increased TGF-α expression and attenuated TMZ-induced apoptotic signaling in TMZ-sensitive M059K cells. <b>Conclusion:</b> Together, our findings demonstrate that the miR-152-3p/TGF-α axis plays a critical role in regulating TMZ sensitivity in GBM, and targeting this pathway may represent a therapeutically relevant signaling axis to overcome chemoresistance.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"19"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.","authors":"Xueping Zhu, Misi He, Ling Wang, Rui Su, Lin Zhong, Ting Guo, Haixia Wang, Dongling Zou","doi":"10.32604/or.2026.083902","DOIUrl":"10.32604/or.2026.083902","url":null,"abstract":"<p><p>Nucleocytoplasmic transport (NCT) regulates the spatial distribution of proteins and RNA between the nucleus and cytoplasm. NCT dysregulation can mislocalize tumor suppressors, DNA-repair factors, transcription factors, and drug targets in cancer. In this review, we conceptualize NCT-dependent protein mislocalization as a spatial regulatory framework for anticancer drug resistance, rather than as a catalogue of transport components. We systematically discuss how nuclear pore complex (NPC) remodeling, transport-receptor imbalance, post-translational modification (PTM)-regulated cargo routing, signaling-NCT crosstalk, nuclear localization signal/nuclear export signal (NLS/NES) alterations, and tumor microenvironmental pressures jointly drive aberrant nucleocytoplasmic distribution. These processes can further regulate apoptosis, DNA-damage repair, oncogenic transcription, oxidative stress adaptation and drug-target accessibility, which ultimately promote drug tolerance and therapeutic resistance. We further distinguish clinically validated mechanisms from preclinical phenotypes and correlative observations. At present, the most advanced therapeutic evidence mainly supports exportin 1/chromosome region maintenance 1 (XPO1/CRM1) inhibition, particularly selinexor in selected hematologic malignancies; in contrast, strategies targeting the NPC, importins, PTM pathways, microenvironmental cues, or localization signals remain largely investigational. By integrating mechanistic, preclinical, translational, and clinical evidence, this review aims to synthesize current evidence on NCT-dependent protein mislocalization as a resistance-relevant axis and to highlight the need for cargo-specific biomarkers and rational combination strategies to translate this biology into anticancer therapy.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"11"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}