International journal of oncology最新文献

{"title":"Triptonide enhances DNA damage by inhibiting TRIP13‑mediated DNA repair and synergizes with bortezomib to suppress multiple myeloma.","authors":"Fen He, Junjun Li, Lijun Peng, Hongyan Zhao, Maoyou Lu, Ruixin Gao, Siqi Wang, Yu Chen, Ruihan Tang, Zhengguo Li, Linlin Zhang, Xinyu Zhang, Qianhao Li, Weihui Chen, Jiayu Liu, Cong Luo, Xi Zeng, Jiliang Xia","doi":"10.3892/ijo.2026.5919","DOIUrl":"10.3892/ijo.2026.5919","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a malignant disorder of plasma cells. Combinations of bortezomib (BTZ) with other therapeutic agents remain the mainstay of MM treatment. However, the rising incidence of drug resistance among patients with MM underscores an urgent need for novel therapeutic strategies. The present study identified triptonide (TN), a small‑molecule monomer extracted from the traditional Chinese herb <i>Tripterygium wilfordii</i> Hook. f., as a synergistic agent that enhanced the anti‑MM activity of BTZ, following a screening of 198 compounds from a ubiquitination‑focused library. TN effectively inhibited cell proliferation, induced apoptosis, and reduced cell viability in MM cells. Furthermore, the synergistic anti‑MM effect between TN and BTZ was validated across MM cell lines, primary MM cells, and xenograft mouse models of MM. Mechanistic investigations revealed that TN synergizes with BTZ by enhancing DNA damage through the suppression of TRIP13‑mediated DNA repair pathways, including non‑homologous end joining and homologous recombination. Notably, TRIP13 knockdown attenuated TN‑induced DNA damage and apoptosis, and diminished the synergistic effect of TN and BTZ on MM cells. Collectively, TN represents a novel anti‑MM agent, and the combination of TN with BTZ constitutes a promising therapeutic strategy for the treatment of MM.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 3","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycolysis‑driven immunosuppression in gastric cancer: Metabolic crosstalk between tumor cells and the immune microenvironment (Review).","authors":"Bo Zhang, Lihan Shang, Ziyu Kuang, Chaoran Wang, Bingsheng Sun, Fanming Kong","doi":"10.3892/ijo.2026.5912","DOIUrl":"10.3892/ijo.2026.5912","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a major cause of cancer‑related mortality worldwide, and only a subset of patients achieves durable benefit from immune checkpoint blockade (ICB). This suggests that non‑genomic barriers within the tumor microenvironment (TME) substantially limit antitumor immunity. Increasing evidence indicates that tumor‑intrinsic glycolytic reprogramming and lactate accumulation contribute to this immune resistance. Oncogenic signaling, hypoxia‑inducible factor‑1α (HIF‑1α), phosphoinositide 3‑kinase/protein kinase B/mechanistic target of rapamycin (mTOR) pathways and noncoding RNA networks promote the expression of glycolytic enzymes and lactate transporters, including hexokinase 2, 6‑phosphofructo‑2‑kinase/fructose‑2,6‑biphosphatase 3 (PFKFB3), pyruvate kinase M2, lactate dehydrogenase A (LDHA) and monocarboxylate transporters, thereby establishing a glycolysis‑high, lactate‑rich TME. Within this metabolic niche, lactate functions as a bioactive mediator that impairs dendritic cell differentiation and cross‑priming, weakens cytotoxic T‑cell and natural killer‑cell activity, and promotes M2‑like macrophages and myeloid‑derived suppressor cells through hydroxycarboxylic acid receptor 1/G protein‑coupled receptor 81‑dependent signaling and histone lactylation. Cancer‑associated fibroblasts and mesenchymal stem/stromal cells further reinforce this state through glycolysis, lactate shuttling, cytokine secretion, extracellular matrix remodeling and exosome‑mediated transfer of glycolysis‑promoting noncoding RNAs. These interactions generate spatially organized immunometabolic niches characterized by lactate accumulation, stromal remodeling, abnormal angiogenesis and poor CD8⁺ T‑cell infiltration. The present review summarizes the molecular drivers of glycolytic reprogramming in GC, the mechanisms by which lactate‑centered crosstalk reshapes stromal and immune compartments, and emerging therapeutic strategies targeting LDHA/monocarboxylate transporter 4, PFKFB3, HIF‑1α/mTOR, epigenetic regulators and repurposed metabolic drugs in combination with programmed death‑1/programmed death‑ligand 1 blockade. It is also discussed how fluorine‑18 fluorodeoxyglucose positron emission tomography/computed tomography, radiomics, glycolysis‑ and lactylation‑related gene signatures, exosomal biomarkers and dynamic metabolic monitoring may support patient stratification and response prediction. Viewing selected GC subtypes through a glycolysis‑centered immunometabolic framework may help guide the rational integration of metabolic and immune interventions to overcome metabolically protected, ICB‑refractory disease.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 3","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T‑box transcription factor 15 regulated by methyltransferase‑like 3‑mediated N6‑methyladenosine modification promotes immune escape and progression of gastric cancer by activating matrix metalloproteinase 14 transcription.","authors":"Hongsai Hu, Rong He, Minji Liu, Xuli Liu, Qiongjia Ai, Min Chen, Qian Wang, Wenhui Chen, Weiming Qu","doi":"10.3892/ijo.2026.5913","DOIUrl":"10.3892/ijo.2026.5913","url":null,"abstract":"<p><p>The present study aimed to investigate the involvement of T‑box transcription factor 15 (TBX15) in the immune evasion by gastric cancer (GC) cells, as well as the molecular pathways that regulate TBX15 upstream and downstream. GC and paracancerous tissues were collected to verify the expression of TBX15, matrix metalloproteinase 14 (MMP14) and methyltransferase‑like 3 (METTL3) using reverse transcription‑quantitative PCR and western blotting. The co‑culture system of GC cell‑tumor‑associated macrophages (TAMs) and mouse forestomach carcinoma (MFC) cell‑CD8⁺ T cells was constructed. TBX15, MMP14 and METTL3 were highly expressed in GC tissues. Kaplan‑Meier analyses were performed, and high <i>TBX15</i> expression predicted a poor prognosis for patients with GC. Silencing <i>TBX15</i> promoted GC cell apoptosis and inhibited tumor development and the activity of proliferation, migration and invasion. TBX15 targeted the <i>MMP14</i> promoter by using ChIP‑qPCR. Overexpression of <i>MMP14</i> attenuated the reduction caused by <i>TBX15</i> silencing. METTL3 targets <i>TBX15</i> mRNA and regulates the m6A level of <i>TBX15</i>. TBX15 is associated with macrophage and CD8⁺ T cell infiltration. In the co‑culture system of GC‑TAM and MFC‑CD8⁺ T cells, <i>TBX15</i> overexpression alleviated the decrease in M2 polarization and activation of CD8⁺ T cell antitumor activity caused by <i>METTL3</i> silencing. However, <i>MMP14</i> overexpression resulted in <i>TBX15</i> silence‑induced decreases in M1 macrophage polarization and CD8⁺ T cell activity. These data suggested that TBX15, correlated with poor prognosis in patients with GC, promotes immune escape in GC cells. TBX15, regulated by m6A methylation, targeted the MMP14 promoter, thereby regulating MMP14 expression. The METTL3/TBX15/MMP14 signaling axis was involved in GC cell development, M2 macrophage polarization and CD8⁺ T cell antitumor activity activation. These findings provide a fundamental experimental rationale for TBX15 as a potential therapeutic target for GC.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 3","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF‑β1 in cancer: From tumour suppressor to promoter, molecular mechanisms, and precision therapeutic strategies (Review).","authors":"Chao Huang","doi":"10.3892/ijo.2026.5914","DOIUrl":"10.3892/ijo.2026.5914","url":null,"abstract":"<p><p>Transforming growth factor‑β1 (TGF‑β1) plays a dual role in cancer progression, acting as both a tumour suppressor and a tumour promoter, with complex and stage‑dependent mechanisms of action. This article systematically reviews the molecular switching mechanism of TGF‑β1 from a tumour suppressor to a tumour promoter and its systemic regulatory network in the tumour microenvironment. In the process through which TGF‑β1 regulates cancer progression, its signalling pathways promote tumour invasion, metastasis and chemotherapy resistance through SMAD mutation, receptor expression downregulation, epithelial‑mesenchymal transition activation, immune escape, non‑SMAD pathway activation and remodelling of the tumour microenvironment. Although TGF‑β1‑targeting therapies such as antibodies, kinase inhibitors and antisense oligonucleotides face limitations in terms of efficacy and toxicity, combination immunotherapy (such as anti‑PD‑1 therapy) has the potential to enhance antitumour responses. Future precision intervention needs to integrate the dimension of time to distinguish between early tumour suppression and late tumour promotion windows, the dimension of spatiality and cell type to analyse the signal heterogeneity between primary and metastatic lesions, the dimension of signalling networks to selectively inhibit SMAD and non‑SMAD pathways, and the dimension of technology, such as using single‑cell sequencing and organoid models to guide personalised treatment, thereby achieving effective regulation of the complex role of TGF‑β1 in cancer progression.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 3","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of deubiquitinating enzymes and their inhibitors in esophageal carcinoma (Review).","authors":"Yu Zhao, Chenghai He, Kexin Chen, Nanting Sun, Ruonan He, Guodong Li","doi":"10.3892/ijo.2026.5921","DOIUrl":"10.3892/ijo.2026.5921","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is a significantly fatal gastrointestinal malignancy worldwide, with complex proteomic remodeling during its onset and progression. Despite advancements in existing multimodal therapy regimens, the prognosis for advanced patients remains inadequate, necessitating the urgent identification of novel therapeutic targets. The Ubiquitin‑proteasome system is the principal regulatory mechanism for intracellular protein homeostasis, with deubiquitinating enzymes (DUBs) serving as crucial 'editors' that reverse ubiquitination modifications, significantly influencing the stability, localization and functional regulation of oncoproteins. This review aims to systematically delineate the complex regulatory network of DUBs in ESCC, comprehensively investigate their specific mechanisms within critical oncogenic signaling pathways, including TGF‑β, Wnt/β‑catenin, NF‑κB and Hippo, as well as their roles in epithelial‑mesenchymal transition, epigenetic remodeling and the regulation of the immune microenvironment. Furthermore, this review provides a novel cross‑cancer perspective by comparing the similarities and differences of DUBs in ESCC and uterine corpus endometrial carcinoma to determine the conserved and tissue‑specific functions of ubiquitin‑specific protease (USP)14, USP7 and BRCA1‑associated protein 1. Furthermore, the preclinical research progress of small molecule inhibitors and proteolysis‑targeting chimeras targeting DUBs was also assessed to identify the theoretical basis and translational pathway for the development of next‑generation precision oncology therapies.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 3","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Retracted] Glycyrrhetinic acid induces G1‑phase cell cycle arrest in human non‑small cell lung cancer cells through endoplasmic reticulum stress pathway.","authors":"Jie Zhu, Meijuan Chen, Ning Chen, Aizhen Ma, Chunyan Zhu, Ruolin Zhao, Miao Jiang, Jing Zhou, Lihong Ye, Haian Fu, Xu Zhang","doi":"10.3892/ijo.2026.5910","DOIUrl":"10.3892/ijo.2026.5910","url":null,"abstract":"<p><p>Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the control β‑actin blots shown in Fig. 3A for the H460 cell line were strikingly similar to the β‑actin blots shown in Fig. 2B for the A549 cell line. In addition, the p16 protein blots shown for the A549 cell line in Fig. 3A were strikingly similar to blots shown for the protein OPN in a paper published subsequently by different authors in the journal <i>Cell & Bioscience</i>. Finally, an independently performed software analysis of the data in this paper undertaken by the Editorial Office revealed that two protein bands positioned adjacent to each other in Fig. 3A (the Cyclin‑D1 blots in the first two lanes for the H460 cell line) were potentially matching, suggesting that the data in this figure may have been handled inappropriately. Given the problems identified with the assembly of data in Fig. 3, and the fact that some of the data in this paper have appeared elsewhere in the scientific literature, the Editor of <i>International Journal of Oncology</i> has decided that it should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 46: 981‑988, 2015; DOI: 10.3892/ijo.2015.2819].</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 3","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP1‑mediated cytoplasmic‑nuclear translocation of SREBP2 promotes colorectal cancer via regulation of cholesterol metabolism.","authors":"Luhui Zhong, Min Sun, Di Wu, Yulan Zeng, Min Zhou, Rui Gong, Feifei Gu, Kai Zhang, Xiaoyan Hu, Yue Hu","doi":"10.3892/ijo.2026.5918","DOIUrl":"10.3892/ijo.2026.5918","url":null,"abstract":"<p><p>Colorectal cancer (CRC) cells reprogram multiple metabolic pathways, including anaerobic glycolysis, lipogenesis and amino acid metabolism, to support their rapid cell division. However, the key regulators driving these metabolic alterations in CRC remain unknown. In the present study, immunohistochemistry staining of a tissue microarray demonstrated that yes‑associated protein 1 (YAP1) was markedly upregulated in CRC tissues and strongly associated with worse patient survival. Knocking down YAP1 inhibited the proliferation and cholesterol accumulation of CRC cells both <i>in vitro</i> cell growth assays and <i>in vivo</i> xenograft model. Mechanistically, western blotting, co‑immunoprecipitation and immunofluorescence assays showed that YAP1 not only transcriptionally upregulated sterol regulatory element binding protein 2 (SREBP2) expression but also physically interacted with it to facilitate its nuclear translocation. This coordinated regulation drove the expression of genes governing <i>de novo</i> cholesterol synthesis and exogenous cholesterol influx. Functional experiments revealed that the SREBP2‑dependent cholesterol metabolic pathway was essential for YAP1‑driven tumorigenesis and proliferation in CRC. These findings uncovered a YAP1‑SREBP2 axis involved in CRC metabolic reprogramming and suggested that targeting this interaction may represent a promising metabolic intervention strategy for CRC management.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 3","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into the physiological, pathological and pharmacological roles of voltage‑gated potassium channel Kv10.1 in cancer (Review).","authors":"Yuxiao Zhen, Weibo Hu, Shanshan Dong, Bochang Wang, Jian Shen, Leyuan Ding, Lifeng Li, Hailong An, Xuzhao Wang, Yafei Chen","doi":"10.3892/ijo.2026.5911","DOIUrl":"10.3892/ijo.2026.5911","url":null,"abstract":"<p><p>Kv10.1, also known as Eag1 or KCNH1, is a voltage‑gated potassium ion channel, which exists in cell membrane and is closely associated with cancer and multiple precancerous lesions. Emerging experimental evidence shows that Kv10.1 is essential for the occurrence, growth, metastasis, proliferation and death of various malignant tumors. The pathogenesis of Kv10.1 and the signal pathways involved in its regulation are different in different cancers. The present review explored the origin, structure, distribution in normal and tumor cells, physiological and pathological characteristics, roles in cancer and tumor regulation mechanisms of Kv10.1. Finally, Kv10.1 related signaling pathways and its current use as a pharmacological modulator are summarized, aiming to provide new insights into the pharmacological research of Kv10.1 in cancer.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 3","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Corrigendum] AHIF promotes glioblastoma progression and radioresistance via exosomes.","authors":"Xuejun Dai, Keman Liao, Zhijun Zhuang, Binghong Chen, Zhiyi Zhou, Sunhai Zhou, Guoshi Lin, Feifei Zhang, Yingying Lin, Yifeng Miao, Zhiqiang Li, Renhua Huang, Yongming Qiu, Ruisheng Lin","doi":"10.3892/ijo.2026.5920","DOIUrl":"10.3892/ijo.2026.5920","url":null,"abstract":"<p><p>Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, in Fig. 2E on p. 264, the Transwell invasion assay results shown in the 'T98G‑AHIF KD' data panel appeared to potentially contain an overlapping section with the 'U251‑NC' data panel in Fig. 3E. After having re‑examined their original data, the authors have realized that Fig. 3 of the above paper was inadvertently assembled incorrectly. The revised version of Fig. 3, now showing replacement data for Fig. 3E (the Transwell results for the U251‑NC and U251‑AHIF‑OE experiments), is featured on the next page. Note that the error made in assembling Fig. 3 did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [International Journal of Oncology 54: 261‑270, 2019; DOI: 10.3892/ijo.2018.4621].</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 3","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).","authors":"Lu Zhang, Dongliang Shen, Jianguo Feng, Liling Tang","doi":"10.3892/ijo.2026.5901","DOIUrl":"10.3892/ijo.2026.5901","url":null,"abstract":"<p><p>Over half of patients with melanoma exhibit v‑Raf murine sarcoma viral oncogene homolog B (BRAF) mutations, which drive hyperactivation of the MAPK pathway and confer high proliferative potential. To target this oncogenic mutation, BRAF inhibitors, as well as MEK inhibitors (targeting the downstream effector of BRAF), have been approved for melanoma therapy. Although these inhibitors initially decrease the tumor burden, nearly all patients eventually develop drug resistance, leading to aggressive disease relapse at both the primary and metastatic sites. Understanding the mechanisms underlying tumor escape from drug lethality is crucial for the development of strategies against melanoma. The present study aimed to summarize the discovery, development and clinical evolution of the BRAF and MEK inhibitors approved for the treatment of melanoma, their notable efficacy in suppressing aggressive melanoma progression and the underlying mechanisms of acquired resistance.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 2","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}