Oncology Letters最新文献

{"title":"Development and validation of a prognostic nomogram incorporating preoperative NLR, CEA and CA19-9 for overall survival in colorectal cancer.","authors":"Bo Shi, Haoran Guo, Junjie Chen, Zhijian Peng, Suo Wang, Guoliang Chen, Qingliang Tai, Xinyu Shi, Songbing He","doi":"10.3892/ol.2026.15673","DOIUrl":"10.3892/ol.2026.15673","url":null,"abstract":"<p><p>Reliable evaluation methods serve an important role in improving the prognosis of patients with colorectal cancer (CRC), guiding the development of treatment plans and prolonging patient survival. In the present study, several preoperative inflammatory indicators and tumor markers were evaluated for their ability to predict CRC prognosis. A total of 224 eligible patients with CRC were enrolled and divided into the training (n=150) and validation (n=74) groups. The training group underwent both Least Absolute Shrinkage and Selection Operator (LASSO) regression and Cox regression analyses to discern pivotal prognostic factors, to formulate a nomogram for overall survival prediction. The results showed that LASSO regression, along with univariate and multivariate Cox regression analyses, identified neutrophil-lymphocyte ratio (NLR), carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) as effective risk factors for CRC. The concordance index of the nomogram was 0.716 in the training group and 0.700 in the validation group. The areas under the curve for predicting 3-year survival were 0.748 and 0.776 in the training and validation groups, respectively, and for 5-year survival were 0.749 and 0.731, respectively. In conclusion, NLR, CA19-9 and CEA may serve as effective additions to traditional clinical assessment methods and a nomogram incorporating these three preoperative indicators could be used efficiently to predict the prognosis of patients with CRC.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"318"},"PeriodicalIF":2.1,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13247392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218694","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":"LATS2 expression differences in lung adenocarcinoma and lung squamous cell carcinoma analyzed using bioinformatics and experimental approaches.","authors":"Zhen Zhang, Shaoyan Zhang, Yalai Xu, Changyu Zhang, Xudong Zhang","doi":"10.3892/ol.2026.15671","DOIUrl":"10.3892/ol.2026.15671","url":null,"abstract":"<p><p>The present study aimed to investigate the role and expression of large tumor suppressor kinase 2 (LATS2) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). The expression levels of LATS2 in LUAD and LUSC, as well as their association with clinical characteristics and patient survival, were analyzed using data obtained from The Cancer Genome Atlas. A total of 100 LATS2-related genes were screened to conduct Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses. The association between LATS2 expression and immune cell infiltration, particularly CD4⁺ and CD8⁺ tumor-infiltrating lymphocytes (TILs), was analyzed. The role of LATS2 in tumor cells was validated by observing the changes in proliferation, apoptosis, migration and invasion of LUAD and LUSC cells following LATS2 overexpression. LATS2 expression was low in both LUAD and LUSC. In LUAD, high expression of LATS2 was associated with lymph node metastasis, distant metastasis and TNM stage and served as an independent risk factor for both overall survival and progression-free survival. Conversely, in LUSC, LATS2 exhibited a weak association with clinical characteristics and survival. In LUAD and LUSC, LATS2-related genes exhibited differences in their associated functional pathways and biological processes. In LUAD, LATS2 was positively associated with CD4⁺ TIL proportions and CD4⁺/CD8⁺ TIL proportions, while exhibiting a negative association with CD8⁺ TIL proportions. In LUSC, no such associations were observed. <i>In vitro</i> experiments demonstrated that overexpression of LATS2 inhibited proliferation, migration and invasion, while promoting apoptosis, in both LUAD and LUSC cell lines, with notably stronger effects observed in LUAD cells. In conclusion, LATS2 exerts tumor-suppressive functions in both LUAD and LUSC. In LUAD, LATS2 is an independent risk factor for patient survival, possibly due to its close association with CD8⁺ TIL levels; however, this relationship is not pronounced in LUSC.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"316"},"PeriodicalIF":2.1,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13247677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218733","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":"Cancer stem cells and their molecular signaling mechanisms in tongue squamous cell carcinoma (Review).","authors":"Xuqiang Guo, Xuan Zhou, Wen Ran, Qiao Zhu, Wei Chen, Chengcheng Ma","doi":"10.3892/ol.2026.15668","DOIUrl":"10.3892/ol.2026.15668","url":null,"abstract":"<p><p>Tongue squamous cell carcinoma (TSCC) remains a significant clinical challenge, owing to its high prevalence and poor prognosis. Cancer stem cells (CSCs) serve a critical role in driving the initiation and progression of TSCC. The present review examined the unique characteristics and functional dynamics of CSCs in TSCC, with particular emphasis on the molecular signaling pathways that regulate their behavior. Key pathways, including Wnt/β-catenin, Notch and Hedgehog signaling pathways, are explored to provide a comprehensive understanding of the mechanisms underlying TSCC. The present study was reported in accordance with the Preferred Reported Items for Systematic Reviews. Articles were sourced from PubMed (pubmed.ncbi.nlm.nih.gov/) using the search terms 'tongue squamous cell carcinoma', 'cancer stem cells', 'molecular signaling', 'Wnt/β-catenin', 'Notch', 'Hotch' and 'Hedgehog', covering the period from January 2001 to October 2025. The review was limited to papers published in English. A total of 437 studies was retrieved. Excluding those studies are not closely related to the topic, 138 were reviewed in detail for their originality and relevance to the broader scope of the present review. By mapping these key signaling networks, the present review aimed to provide a strong foundation for the development of precision therapeutic strategies targeting TSCC.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"313"},"PeriodicalIF":2.1,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13237528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199596","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":"Lectin-captured plasma microRNAs predict response and survival in patients with non-small cell lung cancer treated with nivolumab.","authors":"Eiji Narusawa, Yukiko Nakano, Seshiru Nakazawa, Kanji Hori, Yoichi Ohtaki, Natsuko Kawatani, Tomohiro Yazawa, Ryohei Yoshikawa, Kazuki Numajiri, Ryo Kuriyama, Hiroshi Kurokawa, Yoshihiro Taguchi, Seyed Mostafa Mostafavi Zadeh, Haruka Okami, Takuya Shiraishi, Nobuhiro Nakazawa, Takamichi Igarashi, Kyoichi Kaira, Hiroshi Saeki, Ken Shirabe, Takehiko Yokobori","doi":"10.3892/ol.2026.15669","DOIUrl":"10.3892/ol.2026.15669","url":null,"abstract":"<p><p>Predictive biomarkers for response and post-treatment survival of patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are limited. The present study aimed to evaluate whether recombinant <i>Oscillatoria agardhii</i> agglutinin (OAA)1-enriched plasma microRNAs (miRNAs/miRs) can serve as predictive and prognostic biomarkers in patients with NSCLC treated with nivolumab. High-mannose glycans, enriched in tumors, were selectively captured using this novel lectin. Pre-treatment plasma samples from 48 patients with NSCLC treated with nivolumab, an ICI, were processed using OAA1 columns. Plasma miRNAs were evaluated for their potential roles as predictive markers of response to nivolumab. The levels of circulating miR-320a, miR-320b and miR-3613-5p, which are associated with nivolumab resistance, were quantified with and without OAA1 enrichment. The three miRNAs were significantly upregulated in patients with stable or progressive disease compared with those with a partial response. For miR-320a, this difference was significant only after OAA1 enrichment. Receiver operating characteristic curve and survival analyses showed improved predictive and prognostic performance for OAA1-enriched miRNAs: The area under the curve for miR-3613-5p improved from 0.837 to 0.897, and the hazard ratio increased from 3.386 to 7.815. In conclusion, OAA1-enriched plasma miRNAs may be associated with resistance to nivolumab and a poor prognosis in NSCLC. This glycan-based enrichment strategy could enhance the clinical value of circulating miRNAs and may complement tissue-based biomarkers of ICI response.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"314"},"PeriodicalIF":2.1,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13237519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199630","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":"Pathological response and tumor regression grading following neoadjuvant chemo-immunotherapy and chemotherapy in resectable non-small cell lung cancer.","authors":"Özge Kaya Korkmaz, Yaren Sari Çataldaş, Nazlican Saltik Barel, Mehmet Büyükevli","doi":"10.3892/ol.2026.15667","DOIUrl":"10.3892/ol.2026.15667","url":null,"abstract":"<p><p>Recent neoadjuvant trials in lung cancer have demonstrated meaningful survival advantages, highlighting the need for standardized assessment of pathologic response in resected specimens. Only two systems are currently recommended for evaluating post-treatment response, namely the International Association for the Study of Lung Cancer (IASLC) tumor regression grading system and the immune-related pathologic response criteria (irPRC). The present study aimed to review and apply histopathologic parameters for assessing tumor regression in non-small cell lung carcinoma (NSCLC) specimens resected after neoadjuvant therapy. A total of 30 NSCLC resections obtained after neoadjuvant therapy between 2022 and 2025 were analyzed. Gross and microscopic evaluations were performed according to IASLC recommendations. Residual viable tumor, fibrosis, inflammation and necrosis were semi-quantitatively assessed according to IASLC and irPRC principles. Major pathologic response (mPR) was defined as ≤10% viable tumor and pathologic complete response (pCR) as 0% viable tumor. Associations with demographic features, treatment modalities and survival outcomes were analyzed. Compared with chemotherapy (CT) alone, chemo-immunotherapy (CIT) exhibited a trend toward a deeper pattern of tumor regression, reflected by lower median viable tumor percentages (7.5 vs. 55.0%) and higher mPR rates (62.5 vs. 22.7%), although these differences did not reach statistical significance. pCR occurred in 37.5% of patients treated with CIT and in 13.6% of patients treated with CT. CIT specimens demonstrated more prominent immune-mediated stromal changes, including greater intratumoral inflammation (32.5 vs. 10.0%) and more frequent lymphocytic patterns. Fibrosis strongly correlated with response (P<0.001), whereas necrosis did not. Spread through air spaces positivity was found to be significantly reduced in cases of mPR (P<0.001). Therefore, neoadjuvant CIT may be associated with deeper pathologic regression compared with CT, characterized by increased fibrosis and immune activation. Major pathologic response remains a potential prognostic indicator and integration of IASLC and irPRC criteria, together with tumor microenvironment assessment, may improve the evaluation of treatment response in resectable NSCLC.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"312"},"PeriodicalIF":2.1,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199619","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":"D-salicin induces oxidative stress-mediated ERK1/2 suppression and apoptosis in endometrial cancer cells.","authors":"Neziha Senem Ari, Ayşe Çakir Gündoğdu","doi":"10.3892/ol.2026.15666","DOIUrl":"10.3892/ol.2026.15666","url":null,"abstract":"<p><p>Endometrial cancer is a common gynecologic malignancy for which therapeutic options remain limited in advanced or treatment-resistant disease. Natural compounds that selectively perturb cancer-associated redox signaling and survival pathways may offer novel anticancer strategies. The present study investigated the anticancer effects of D-salicin in the endometrial adenocarcinoma-derived Ishikawa cell line, with a focus on oxidative stress and extracellular signal-regulated kinase (ERK)1/2 signaling, and assessed cancer selectivity using normal human dermal fibroblasts (HDF). D-salicin selectively reduced Ishikawa cell viability in a concentration-dependent manner while largely sparing HDF. This cytotoxic effect was accompanied by marked intracellular reactive oxygen species (ROS) accumulation, increased lipid peroxidation (MDA) and depletion of total glutathione (GSH), indicating induction of oxidative stress. Elevated oxidative burden was associated with caspase-3 activation and concentration-dependent suppression of ERK1/2 phosphorylation, both of which were attenuated by N-acetylcysteine (NAC) co-treatment. To determine redox dependence, NAC was incorporated as an antioxidant co-treatment. D-salicin induced a significant, concentration-dependent reduction in Ishikawa cell viability (P<i><</i>0.0001), whereas HDF viability remained largely preserved across the tested range (P>0.05). In Ishikawa cells, D-salicin markedly increased intracellular ROS in a dose-dependent manner (P≤0.01) and this effect was markedly attenuated by NAC co-treatment (P≤0.01), indicating an NAC-sensitive oxidative component. Consistent with redox disruption, D-salicin increased MDA levels and depleted total GSH in Ishikawa cells (P≤0.01). Elevated oxidative stress was accompanied by increased caspase-3 levels (P≤0.01), supporting engagement of apoptotic signaling. Moreover, D-salicin markedly suppressed ERK1/2 phosphorylation in Ishikawa cells (P<i><</i>0.0001), while ERK signaling was not markedly altered in HDF cells (P>0.05). Notably, NAC co-treatment partly restored p-ERK1/2 levels under the IC₅₀ condition (P<i><</i>0.01 vs. D-salicin alone), supporting a redox-linked contribution to ERK pathway modulation. Collectively, these findings indicated that D-salicin exerts selective anticancer effects in endometrial cancer cells by inducing oxidative stress and disrupting ERK1/2-mediated survival signaling, with NAC-sensitive modulation consistent with involvement of a redox-responsive ROS-ERK axis.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"311"},"PeriodicalIF":2.1,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199663","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":"Decoding the role of polyamine metabolism in lung adenocarcinoma prognosis: A triangulated approach combining transcriptome, single-cell and Mendelian randomization analyses.","authors":"Hua Yang, Lemeng Zhang, Jianhua Chen, Junjie Zhang","doi":"10.3892/ol.2026.15665","DOIUrl":"10.3892/ol.2026.15665","url":null,"abstract":"<p><p>The progression of lung adenocarcinoma (LUAD) is influenced by polyamine metabolism, which modulates antitumor immunity, although the underlying mechanisms remain unclear. The present study investigates the role of polyamine metabolism-related genes (PMRGs) in LUAD using transcriptomic data, single-cell RNA sequencing (scRNA-seq) and Mendelian randomization. Differentially expressed PMRGs were identified through differential expression analysis and weighted gene co-expression network analysis. Prognostic genes were selected via Cox regression and least absolute shrinkage and selection operator regression to construct a risk model. Immune infiltration, machine learning and scRNA-seq were employed to explore molecular mechanisms whilst reverse transcription-quantitative PCR (RT-qPCR) validated gene expression in LUAD tissues. A nomogram incorporating risk scores assisted in predicting LUAD prognosis (area under the curve >0.6). Distinct immune cell profiles, particularly involving B cells and CD4⁺ T cells, were observed between high- and low-risk groups. Drug sensitivity analysis identified 15 drugs with differential responses. Epithelial cells emerged as a key cluster, with dynamic changes in calcium voltage-gated channel auxiliary subunit α2δ2 (CACNA2D2) expression during pseudotime. RT-qPCR confirmed the downregulation of prognostic genes in LUAD. A polyamine metabolism-related prognostic signature (CACNA2D2, adenoreceptor β-1, immunoglobulin superfamily member 10 and carbonic anhydrase 4) associated with the tumor microenvironment was established, offering potential for enhanced prognosis prediction in LUAD.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"310"},"PeriodicalIF":2.1,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199667","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":"Histopathological changes in primary extramammary Paget disease with emphasis on syringomatous structures and syringocystadenocarcinoma papilliferum <i>in situ</i>-like changes.","authors":"Yutaro Fukuma, Mitsuaki Ishida, Yoshinobu Hirose","doi":"10.3892/ol.2026.15662","DOIUrl":"10.3892/ol.2026.15662","url":null,"abstract":"<p><p>Primary extramammary Paget disease (PEMPD) is a rare adenocarcinoma, and is histopathologically characterised by intraepithelial proliferation of carcinoma cells with abundant amphophilic cytoplasm. Minor histopathological findings in PEMPD, including syringomatous structures and syringocystadenocarcinoma papilliferum (SCACP) <i>in situ</i>-like changes, have rarely been reported. The present study aimed to analyse histopathological changes in PEMPD. Consecutive patients with PEMPD who underwent surgical resection were included. Melanin within carcinoma cell cytoplasm, syringomatous structures and SCACP <i>in situ</i>-like changes were assessed on haematoxylin and eosin-stained slides. Overall, 55 patients (16 female and 39 male patients) were included; 23 patients (41.8%) had an invasive carcinoma component and the remainder had only <i>in situ</i> lesions. Melanin pigment within carcinoma cell cytoplasm was observed in 85.5% of patients, while 17.4% of patients with invasive PEMPD exhibited melanin pigment in invasive carcinoma cells. Syringomatous structures, characterised by ductal, tadpole-like or small cystic structures composed of bland epithelial cells, were observed in 9.1% of patients (31.3% of all female patients), including in areas outside the PEMPD lesions. SCACP <i>in situ</i>-like changes, characterised by papillary epidermal hyperplasia with replacement of carcinoma cells, were also observed in 9.1% of PEMPD cases. These findings demonstrated that a high frequency of the presence of melanin pigment within carcinoma cell cytoplasm, including in invasive carcinoma cells, could lead to misdiagnosis as malignant melanoma. Additionally, syringomatous structures (especially in female patients) and SCACP <i>in situ</i>-like changes may lead to the misdiagnosis of syringoma and SCACP <i>in situ</i>, respectively. Therefore, recognition of these histopathological changes in PEMPD is required for accurate diagnosis.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"307"},"PeriodicalIF":2.1,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13227319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157612","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":"Targeting non-small cell lung cancer: Molecular mechanisms and clinical studies (Review).","authors":"Ying Luo, Guofang Yin, Xiaoqin Luo, Yue Liu, Kaiyu Jin, Zhiguo Wang","doi":"10.3892/ol.2026.15663","DOIUrl":"10.3892/ol.2026.15663","url":null,"abstract":"<p><p>Over the past two decades, notable advances have been made in the treatment of non-small cell lung cancer (NSCLC), as well as in the elucidation of molecular mechanisms and the development of novel therapeutics (for example, targeted therapy and immunotherapy), whose clinical benefits have been documented. The epidermal growth factor receptor and anaplastic lymphoma kinase are well-known tumor targets; both can promote tumor growth through PI3K/AKT/mTOR pathway. Other oncogenes and tumor suppressor genes such as Kirsten rat sarcoma and tumor protein 53 have also been investigated. The notable immune checkpoints are programmed cell death protein-1/programmed cell death ligand-1 and cytotoxic T-lymphocyte-associated protein 4. However, the overall survival rate of patients with NSCLC is still low due to primary or acquired drug resistance, which is associated with abnormal signaling pathways. In particular, patients with advanced disease who have non-druggable targets or lack an immune response have a poor prognosis, such as the mutation of serine/threonine kinase 11, also known as liver kinase B1 (LKB1). LKB1 impacts cellular energy metabolism and the tumor immune microenvironment, resulting in little benefit from current therapies. Therefore, further research into more effective treatments is warranted to potentially improve the outcomes of patients with NSCLC in the future.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"308"},"PeriodicalIF":2.1,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13227321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157585","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":"Durable response to selpercatinib in HOOK3-RET fusion positive, α-fetoprotein producing metastatic pancreatic ductal adenocarcinoma with intestinal-type differentiation.","authors":"Harsahib Singh Sandhu, Aparna Natarajan, Smiley Joshi","doi":"10.3892/ol.2026.15661","DOIUrl":"10.3892/ol.2026.15661","url":null,"abstract":"<p><p>Pancreatic cancer carries a poor prognosis, with few effective treatment options available. Various rearranged during transfection (RET) proto-oncogene fusions have been found in a small fraction of pancreatic cancers; however, the hook microtubule tethering protein 3 (HOOK3)-RET fusion has not yet been reported in the medical literature. The HOOK3-RET fusion was observed in a case of α-fetoprotein (AFP)-producing pancreatic ductal adenocarcinoma with widespread hepatic and lymph node metastasis in a 51-year-old South Asian male. The patient's serum carbohydrate antigen 19.9 was mildly elevated: 96.28 U/ml (normal, <37 U/ml), but the serum AFP level was very high (16,410.0 ng/ml; normal, <6.6 ng/ml). The patient did not respond to gemcitabine and cisplatin-based systemic chemotherapy. Next-generation sequencing of the patient's biopsy sample revealed a HOOK3-RET fusion. RET proto-oncogene fusions trigger a cascade of oncogenic signals, which promote the proliferation and survival of cancer cells. Selpercatinib, a selective inhibitor of receptor tyrosine kinase RET, blocks RET kinase activity by binding to its adenosine triphosphate-binding site, thus preventing the kinase from phosphorylating substrates and halting oncogenic signaling. The patient was treated with selpercatinib, which produced a durable response lasting over 15 months in this chemotherapy-refractory patient, highlighting the efficacy of selpercatinib in HOOK3-RET fusion-positive pancreatic cancer.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"306"},"PeriodicalIF":2.1,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13227577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157647","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}