International journal of oncology最新文献

{"title":"Pancreatic cancer EMT‑targeted therapy: Molecular mechanisms and clinical translation (Review).","authors":"Guirui Zhang, Yongmo Wu, Mingzhen Wei, Shupeng Huang, Qinghao Wang, Zhengyi Xie, Sisi Liu, Jin Wang","doi":"10.3892/ijo.2026.5867","DOIUrl":"10.3892/ijo.2026.5867","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a dismal 5‑year survival rate of ~9%, primarily due to late diagnosis, aggressive metastasis and profound resistance to conventional therapies. Epithelial‑mesenchymal transition (EMT) has been identified as a pivotal driver of these malignant phenotypes, facilitating early invasion, dissemination and treatment failure. The present review systematically elaborated on the multidimensional mechanisms underlying EMT in PDAC, emphasizing its operation as a spectrum of hybrid epithelial/mesenchymal states rather than a binary switch. Key molecular mechanisms include the activation of core transcription factors (such as Snail, ZEB, Twist), intricate crosstalk within the tumor microenvironment (such as transforming growth factor-β and hepatocyte growth factor signaling from stromal cells) and dynamic epigenetic reprogramming. Furthermore, EMT critically contributes to the acquisition of cancer stem cell properties and enhances the survival and colonization of circulating tumor cells. The present review also outlined emerging translational strategies targeting EMT‑related pathways, highlighting agents such as STNM01 that have entered early-phase clinical trials. By synthesizing unprecedented insights into EMT's plastic spectrum states and subtype‑specific regulatory networks, this work establishes a paradigm‑shifting framework for advancing EMT‑targeted therapies; offering transformative potential to overcome PDAC's historical therapeutic barriers and substantially improve patient survival outcomes. By synthesizing current insights from molecular pathways to therapeutic applications, the present review confirmed EMT as a promising therapeutic target and provides a strategic framework for advancing PDAC treatment, with the ultimate goal of improving clinical outcomes.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"68 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365166","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":"Therapeutic implications of targeting cancer testis antigen MAGEA1 in cervical cancer.","authors":"Ayoung Kim, Jina Kim, Woori Kwak, Kyumin Mo, Soohyun Choe, Minyeong Jeon, Jisun Lee, Jun-Won Yun, Hyunho Yoon","doi":"10.3892/ijo.2026.5870","DOIUrl":"10.3892/ijo.2026.5870","url":null,"abstract":"<p><p>MAGE family member A1 (MAGEA1), a cancer‑testis antigen (CTA), is aberrantly expressed in several malignancies such as lung and liver cancers. However, its role in cervical cancer remains to be elucidated. The present study investigated the functional significance and therapeutic potential of MAGEA1 in cervical cancer using lentiviral short hairpin RNA‑mediated knockdown, a series of functional assays, RNA sequencing (RNA‑seq), and nude mouse xenograft models. It was found that MAGEA1 was upregulated in cervical cancer cells and its knockdown substantially suppressed cell proliferation, migration, invasion, and <i>in vivo</i> tumor growth. RNA‑seq analysis further revealed that MAGEA1 silencing altered pathways related to apoptosis, DNA repair, and metabolism. Moreover, MAGEA1 knockdown enhanced chemosensitivity, indicating a potential role in mediating drug resistance. Collectively, the findings identified MAGEA1 as a key oncogenic driver in cervical cancer and highlighted its promise as both a prognostic biomarker and a therapeutic target, offering novel avenues for personalized treatment strategies in cervical cancer.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"68 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443656","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":"Diverse roles of SERPINE1 in regulating cellular proliferation and invasion.","authors":"Wei Wang, Pengfei Zhao, Tian Wang, Weijing Wu, Jing Li, Qiang Huang, Jing Mo","doi":"10.3892/ijo.2026.5871","DOIUrl":"10.3892/ijo.2026.5871","url":null,"abstract":"<p><p>Serine protease inhibitor clade E member 1 (SERPINE1) is involved in various biological processes, but its role in promoting or suppressing tumorigenesis remains controversial. The present study focused on the effects of SERPINE1 downregulation on cell proliferation and invasion across three types of tumors to elucidate the underlying mechanisms. Based on data from an analysis of The Cancer Genome Atlas dataset, high SERPINE1 levels in patients with breast cancer and low‑grade glioma were associated with a poor prognosis, whereas elevated SERPINE1 expression in patients with skin cutaneous melanoma associated with improved outcomes. With respect to cell proliferation phenotypes, SERPINE1 knockdown increased xenograft growth and the proliferation of melanoma C918 cells by promoting cell cycle progression through the modulation of minichromosome maintenance complex component 3 and the activity of p53/SMAD3 regulators; conversely, SERPINE1 knockdown reduced the xenograft growth and proliferation of MDA‑MB‑231 breast cancer cells by decreasing the urokinase‑type plasminogen activator receptor‑mediated ERK/p38 activity ratio and similarly decreased proliferation in H4 glioma cells through an heat shock protein 90‑alpha (HSP90α)‑mediated reduction in the ERK/p38 activity ratio. Regarding invasion and metastasis, SERPINE1 knockdown consistently reduced invasion, matrix metalloproteinase (MMP) activity, and lung metastasis in both C918 and MDA‑MB‑231 cells but paradoxically increased invasion and MMP‑1 activity in H4 cells through the HSP90α‑p38‑MMP‑1 axis. Collectively, these findings suggested that SERPINE1 exerts diverse effects on cell proliferation and invasion through multiple regulatory mechanisms. These findings indicated that therapy targeting SERPINE1, which involves a comprehensive understanding of its diverse mechanisms of function, can increase treatment precision and reduce adverse reactions.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"68 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443677","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":"FOXM1 inhibitor, RCM‑1, enhances venetoclax mediated apoptosis through downregulation of ATP2B4 in rhabdomyosarcoma.","authors":"Nawal Merjaneh, Ying-Wei Lan, Zicheng Deng, Johnny Donovan, Guolun Wang, Jonathan Do, Tiffany Juan, Xiaomei Xia, Vladimir V Kalinichenko, Tanya V Kalin","doi":"10.3892/ijo.2026.5865","DOIUrl":"10.3892/ijo.2026.5865","url":null,"abstract":"<p><p>Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. Intensifying chemotherapy has failed to improve patient survival for metastatic or relapsed RMS and RMS survivors often suffer from significant long‑term toxicities. More efficient and less toxic new therapies are critically needed. RMS expresses high levels of anti‑apoptotic protein Bcl‑2 and an oncogenic transcription factor Forkhead box protein M1 (FOXM1), which is also known to inhibit tumor cell apoptosis. The present study used a combination therapy of a recently developed non‑toxic FOXM1 inhibitor, RCM‑1 and the FDA‑approved Bcl2 inhibitor, venetoclax, which is not effective as a monotherapy in solid tumors. Compared with venetoclax alone, the combination therapy efficiently inhibited RMS growth in the animal model by decreasing tumor cell proliferation and inducing tumor cell apoptosis. RNA‑sequencing analysis demonstrated that the combination therapy uniquely decreased expression of ATPase Plasma Membrane Ca²⁺ Transporting 4 (ATP2B4), a plasma membrane calcium channel that is highly expressed in RMS compared with normal muscle cells. RCM‑1, but not venetoclax treatment, inhibited ATP2B4 and enhanced the sensitivity of RMS cells to apoptosis. Knockdown of <i>ATP2B4</i> decreased RMS tumor cell proliferation, migration and colony formation <i>in vitro</i>. Furthermore, knockdown of <i>ATP2B4</i> increased tumor cell apoptosis, while overexpression of <i>ATP2B4</i> decreased tumor cell apoptosis <i>in vitro</i>. In the animal model of RMS, depletion of <i>ATP2B4</i> decreased tumor growth. In summary, combining RCM‑1 with venetoclax sensitized RMS cells to apoptosis by decreasing ATP2B4. This made ATP2B4 a promising therapeutic target for RMS and provides a rationale for exploring this combination in early‑stage clinical trials.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"68 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12987556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365127","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":"Role of histone modifications in gastric cancer (Review).","authors":"Ying Zhang, Lili Wang, Ling Wang, Zefen Li, Ruiying You, Xueping Meng, Yazhen Gao, Leyi Zhu, Shufei Wei, Meiren Li","doi":"10.3892/ijo.2026.5878","DOIUrl":"10.3892/ijo.2026.5878","url":null,"abstract":"<p><p>Histone modification is an important mechanism of epigenetic regulation. New histone modifications play key roles in the regulation of gene expression and in the development and progression of various diseases. In addition to histone modifications, epigenetic regulation includes classic pathways such as DNA methylation, chromatin remodeling complexes and non‑coding RNAs, which interact with each other and jointly shape the occurrence and development of gastric cancer (GC). The present study systematically elaborated on the role of histone modification in GC and introduced several main types of histone modification, including acetylation, methylation, citrullination, ubiquitination and lactylation, focusing on histone lactylation modification and exploring its biochemical basis, interaction with other modifications and functions such as metabolic reprogramming, cell proliferation, migration and immune escape, covering non‑tumor and other cancer fields. On this basis, the specific application of histone modification (acetylation, methylation and other modifications) in GC is further explained and the effects of histone lactylation on metabolic reprogramming, proliferation, migration and immune escape of GC are analyzed in detail. Finally, the clinical significance of histone lactylation modifications in the diagnosis and prognosis of GC, biomarkers, therapeutic targets and drug resistance mechanisms provides a reference for an in‑depth understanding of the role of histone modifications, especially lactylation modifications, in the development of GC and clinical transformation applications.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"68 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608697","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":"Enolase 1: A paradigm of metabolic enzyme moonlighting in tumorigenesis (Review).","authors":"Xiaochen Ni, Mingsi Zhang, Kaiyuan Zhang, Chuhang Wang, Jianing Guo, Wei Fan, Linfeng Zheng, Tao Jiang, Guangji Zhang","doi":"10.3892/ijo.2026.5869","DOIUrl":"10.3892/ijo.2026.5869","url":null,"abstract":"<p><p>Enolase 1 (ENO1) plays a pivotal role in tumor development, recognized as a multifunctional oncogene across diverse cancers. Initially known for its central role in glycolysis, where it catalyzes the conversion of 2‑phosphoglycerate to phosphoenolpyruvate, the influence of ENO1 extends far beyond. Recent studies have unveiled its additional roles in promoting tumor progression through plasminogen receptor activity, nucleic acid binding activity and signaling functions. The function of ENO1 is intricately regulated by a wide array of post‑translational modifications, such as phosphorylation, ubiquitination, acetylation, methylation, succinylation and glycosylation. These modifications fine‑tune its enzymatic activity, stability and subcellular localization, thereby affecting tumor behavior. ENO1 holds significant diagnostic and prognostic value, with its expression levels closely linked to tumor malignancy and patient survival outcomes. In preclinical models, multiple therapeutic approaches targeting ENO1 have demonstrated tumor progression‑inhibiting effects. Consequently, drug development efforts centered on ENO1 are gaining momentum, with anticancer agents targeting this protein showing promising potential. As ENO1 emerges as a novel therapeutic target in oncology, the present review summarizes the latest research progress on ENO1 in the field of cancer.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"68 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443738","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":"Smoking promotes colorectal cancer via the CKAP2L/AREG axis.","authors":"Shasha Wu, Feixiang Wu, Xiaoqing Li, Zhihang Jiang, Fuqiang Liu, Zheng Jiang","doi":"10.3892/ijo.2026.5872","DOIUrl":"10.3892/ijo.2026.5872","url":null,"abstract":"<p><p>The link between smoking and colorectal cancer (CRC) is well‑established; however, further research is needed to fully understand the specific effects of tobacco on the development of this type of cancer. The aim of the present study was to investigate the relationship between smoking and CRC, as well as to identify key genes involved in smoking‑enhanced CRC progression. To confirm the association between smoking and CRC, analyses of clinical data from the National Health and Nutrition Examination Survey database and genome‑wide association studies data were integrated. In addition, RNA sequencing (RNA‑seq) was conducted on HCT116 cells treated with cigarette smoke extract to identify genes related to smoking. To evaluate the malignant phenotypes of CRC cells and potential molecular mechanisms by which key genes promote smoking‑enhanced CRC, a series of cell and animal experiments were performed. The positive association between smoking and CRC was confirmed by both the cross‑sectional study and Mendelian randomization analyses. Furthermore, after treatment of CRC cells with cigarette smoke extract, cell proliferation, migration and invasion were enhanced. Subsequently, cytoskeleton‑associated protein 2‑like (CKAP2L) was filtered out by bioinformatics analysis, indicating its involvement in smoking‑enhanced CRC. After suppressing CKAP2L, the results revealed that cell proliferation was inhibited, and the cell cycle was arrested at S and G2/M phases. Moreover, cell migration and invasion were suppressed after suppressing CKAP2L expression. Further RNA‑seq analysis suggested that CKAP2L promotes the expression of amphiregulin (AREG). Subsequently, the suppression of AREG resulted in a reduction in the CKAP2L‑promoted proliferation and migration of CRC cells. The results of a chromatin immunoprecipitation assay further confirmed that signal transducer and activator of transcription 3 (STAT3) regulated the transcriptional level of AREG by binding to its promoter. In addition, CKAP2L increased the phosphorylation of STAT3, which subsequently activated the AREG/EGFR pathway, leading to the progression of CRC. In conclusion, the present study demonstrated that smoking may promote CRC progression through the CKAP2L/AREG axis.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"68 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443746","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] Leptin promotes breast cancer cell migration and invasion via IL‑18 expression and secretion.","authors":"Kuangfa Li, Lan Wei, Yunxiu Huang, Yang Wu, Min Su, Xueli Pang, Nian Wang, Feihu Ji, Changli Zhong, Tingmei Chen","doi":"10.3892/ijo.2026.5864","DOIUrl":"10.3892/ijo.2026.5864","url":null,"abstract":"<p><p>Following the publication of the above article and an Expression of Concern statement that was issued in light of concerns raised by an interested reader (doi: 10.3892/ijo.2025.5816) regarding potential duplications of data comparing Figs. 1D and 2E, and the apparent re‑use of β‑actin control data in Fig. 4A and B where different experimental conditions were reported, the authors have now responded to the enquiry posed by the Editorial Office. After consulting their original data, the authors have realized that the data in Fig. 2E for the MDA‑MB‑231 cell line, and the β‑actin blots in Fig. 4B, were chosen incorrectly (it was also noted by the Editorial Office, upon performing an independent analysis of the data in this paper, that, in Fig. 6C, the CD68/Lep. and CD163/CNL.+Lep. data panels appeared to contain an overlapping section of data, such that the data shown in these panels may have been derived from the same original source). The revised versions of Figs. 2 and 4 (showing the correct data for the MDA‑MB‑231 cell line in Fig. 2E and the β‑actin blots in Fig. 4B) are shown on the next two pages. Furthermore, a revised version of Fig. 6, showing replacement data for the CD68/Lep. data panel, is also shown on the third page. Note that the errors made in assembling these figures did not affect the overall results and conclusions reported in the paper. The authors are grateful to the Editor of <i>International Journal of Oncology</i> for granting them the opportunity to publish this corrigendum, and all the authors agree with its publication; furthermore, they apologize to the readership of the journal for any inconvenience caused. [International Journal of Oncology 48: 2479‑2487, 2016; DOI: 10.3892/ijo.2016.3483].</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"68 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12987563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365095","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] The p85α regulatory subunit of PI3K mediates cAMP‑PKA and retinoic acid biological effects on MCF7 cell growth and migration.","authors":"Caterina F Donini, Erika Di Zazzo, Candida Zuchegna, Marina Di Domenico, Sonia D'Inzeo, Arianna Nicolussi, Enrico V Avvedimento, Anna Coppa, Antonio Porcellini","doi":"10.3892/ijo.2026.5852","DOIUrl":"10.3892/ijo.2026.5852","url":null,"abstract":"<p><p>Following the publication of the above article, an interested reader drew the authors' attention to the fact, for the wound‑healing assay data shown in Fig. 6 on p. 1632, the 'T16 h/p85 WT' and 'T16 h + RA/p85 D' panels appeared to contain an overlapping section, such that data which were intended to show the results of differently performed experiments had apparently been derived from the same original source. Upon contacting the authors, they realized that Fig. 6 had been inadvertently assembled incorrectly. The revised version of Fig. 6, now showing the correct data for the 'T16 h + RA/p85 D' panel, is shown on the next page. Note that this error did not affect the overall conclusions reported in the study. The authors are grateful to the Editor of <i>International Journal of Oncology</i> for allowing them this opportunity to publish a Corrigendum, and all the authors agree with its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 40: 1627‑1635, 2012; DOI: 10.3892/ijo.2012.1383].</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"68 4","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12920012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124943","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":"Beyond the membrane: Internalization and compartmentalization of insulin‑like growth factor 1 receptor signaling in cancer pathogenesis and treatment (Review).","authors":"Tiehong Zhang, Ling Li, Chunling Du","doi":"10.3892/ijo.2026.5857","DOIUrl":"10.3892/ijo.2026.5857","url":null,"abstract":"<p><p>The insulin‑like growth factor 1 receptor (IGF‑1R) plays a central role in tumor initiation, progression and response to treatment. IGF‑1R internalization and compartmentalization have profound effects on tumor biology, extending beyond classical signaling associated with receptors at the cell membrane. Following internalization, IGF‑1R alters its intracellular localization and induces new signaling functions. These changes affect the duration and spatial dynamics of signal activation, thereby influencing tumor cell proliferation, migration and the development of drug resistance. However, the exact molecular mechanisms that mediate these processes remain elusive, and the inherent complexity of the downstream signaling network continues to limit the clinical translation of IGF‑1R‑targeted therapies. The present review systematically summarizes the current knowledge on the molecular mechanisms of IGF‑1R internalization and compartmentalization, highlighting their roles in tumor progression and treatment response. The recent advancements and persistent challenges in this field are also critically discussed, aiming to provide a theoretical foundation and new insights for the development of more efficient and effective therapeutic plans that specifically target IGF‑1R.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"68 4","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226794","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}