Medical Oncology最新文献

{"title":"Targeting autophagy to enhance cancer immunotherapy: emerging mechanisms and strategies.","authors":"Jawza A Almutairi","doi":"10.1007/s12032-025-03081-w","DOIUrl":"https://doi.org/10.1007/s12032-025-03081-w","url":null,"abstract":"<p><p>Autophagy plays a dual role in cancer, supporting tumor cell survival while influencing immune escape, which can limit the efficacy of current immunotherapies. Modulating autophagy in tumor or immune cells offers a promising strategy to overcome resistance and enhance antitumor immunity. However, a deeper mechanistic understanding of how autophagy shapes the tumor immune landscape is essential to identify selective therapeutic targets, as reviewed here. In this review, we also present the emerging approaches, including tumor-specific inhibitors, nanoparticles, and genetic tools, that aim to precisely modulate autophagy while preserving immune function. Integrating insights from immuno-oncology and cellular metabolism may accelerate the development of combinatorial strategies and facilitate clinical translation of autophagy-targeted immunotherapies.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"520"},"PeriodicalIF":3.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer Metastasis: Therapeutic Challenges and Opportunities.","authors":"Sri Sathya Sandilya Garemilla, Manisha Choudhary Kadambala, Siri Chandana Gampa, Swetha Chinthala, Sireesha V Garimella","doi":"10.1007/s12032-025-03072-x","DOIUrl":"10.1007/s12032-025-03072-x","url":null,"abstract":"<p><p>Metastatic cancer is the leading cause of cancer-related mortality, responsible for nearly 90% of deaths worldwide. Its progression depends on a multistep cascade involving invasion, vascular dissemination, survival in circulation and colonization of distant organs. This process is highly inefficient yet devastating, as a small fraction of tumor cells can establish lethal secondary lesions. This review summarizes recent advances in understanding the biological complexities of metastasis, including tumor heterogeneity, chemoresistance and the tumor microenvironment. We further examine emerging diagnostic and therapeutic strategies, spanning molecular profiling, liquid biopsies, nanomedicine, immunotherapy and artificial intelligence. Targeted therapies toward inhibiting metastasis such as BRAF/MEK inhibitors have extended progression-free survival by 30-40% in melanoma trials, while checkpoint inhibitor combinations (PD-1 and CTLA-4) achieve response rates exceeding 50% in melanoma and renal cell carcinoma. Liquid biopsy platforms enable real-time detection of resistance mutations, and nanoparticle-based drug delivery systems improve drug accumulation at tumor sites. Emerging tools such as organoids and tumor-on-a-chip models enhance predictive accuracy, while AI-driven analytics integrate multi-omics data to refine patient stratification. Integrating these innovations into next-generation clinical trials will require biomarker-driven patient selection, multi-center validation of assays and regulatory frameworks to accelerate approval. Together, these advances represent a transition toward personalized and adaptive care, offering the potential to redefine metastatic cancer as a manageable condition rather than a terminal diagnosis.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"518"},"PeriodicalIF":3.5,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selectively targeting the IKKβ by 11,11'-methylenebisdibenzo[a, c]phenazine (SIKB-7543) downregulates aberrant NF-κB signaling to control the proliferation and induce apoptosis in Hodgkin lymphoma.","authors":"Mohammad Abohassan, Mesfer Mohammad Al Shahrani, Sarah Khaled AlOuda, Prasanna Rajagopalan","doi":"10.1007/s12032-025-03073-w","DOIUrl":"https://doi.org/10.1007/s12032-025-03073-w","url":null,"abstract":"<p><p>Hodgkin lymphoma (HL) develops in the part of the immune system that is centrally aggravated by the NF-κB signaling. Selectively targeting IKKβ to downregulate the NF-κB-mediated disease progression helps control this dreadful malignancy. This study evaluated novel and selective IKKβ inhibitors to downregulate aberrant NF-κB signaling in HL. GROMACS, GMX_MMPBSA, and PLIP were used after high-throughput virtual screening against the ChemBridge library to identify leads. The in vitro effectiveness was evaluated using flow cytometry, luminometry, and spectrometry on RPMI 666 and Hs 445 cells. HTVS identified SIKB-7543 with favorable binding affinities of -14.2 kcal/mol toward IKKβ. MD simulations established stable bonding for SIKB-7543 and IKKβ with RSMD values around 0.07 nm. The ΔG binding calculation was -50.46 kcal/mol, favoring sturdy binding. ADME analysis favored small-molecule characteristics. SIKB-7543 inhibited IKKβ activity with an IC₅₀ value of 118 nM. The compound effectively controlled the proliferation of RPMI 666 and Hs 445 cells with GI₅₀ values of 345.6 nM and 320.5 nM, respectively. SIKB-7543 prompted dose-responsive apoptosis in the HL cells. Cell-cycle analysis demonstrated a concentration-dependent increase in the sub-G₀ population in both cell lines following SIKB-7543 treatment, while decreasing the NF-κB-p65 (Rel A) positive populations in TNFα-stimulated RPMI 666 and Hs 445 cells dose-dependently. Results suggest SIKB-7543 is a selective IKKβ inhibitor that downregulates aberrant NF-κB signaling, controls proliferation, and induces apoptosis, warranting further preclinical developments to counter HL malignancy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"519"},"PeriodicalIF":3.5,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimetastatic effects of chamuangone-enriched extract in breast cancer lung metastasis: in vitro and in vivo evidence.","authors":"Asad Ur Rahman, Naveed Ullah Khan, Jiang Ni, Pharkphoom Panichayupakaranant","doi":"10.1007/s12032-025-03076-7","DOIUrl":"https://doi.org/10.1007/s12032-025-03076-7","url":null,"abstract":"<p><p>Breast cancer lung metastasis (BCLM) is the most lethal form of breast cancer (BC). Current treatments are costly and often associated with severe side effects, emphasizing the need for alternative therapies. A chamuangone-enriched extract (CEE), quantitatively standardized by HPLC to contain 73.0 ± 2.0% w/w chamuangone, was developed from the leaves of the Thai vegetable Garcinia cowa and evaluated for its anticancer efficacy. Both in vitro and in vivo studies were conducted using MCF-7 cells in a human breast cancer xenograft model. Histopathological examination of the tumor and lungs, as well as expression of BCLM markers (ER, PR, Ki-67, CD44, IL-6, TNF-α, VEGFA, E-cadherin, and N-cadherin) expression in the tumor and lungs were evaluated through immunohistochemistry. In vitro studies, CEE at a concentration of 10 µg/mL inhibited MCF-7 cell growth and migration, induced apoptosis, and significantly modulated apoptotic and inflammatory markers (p53 and Bcl-2, MMP-2, MMP-9, IL-6, and TNF-α) in MCF-7 cells. In vivo studies, CEE (100 mg/kg bodyweight) significantly inhibited tumor growth and decreased the expressions of BCLM markers in tumor and lung tissues, resulting in the suppression of BC and metastasis. These results support the potential medicinal and protective use of CEE as a functional ingredient for mitigating the devastating effects of BC and BCLM.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"517"},"PeriodicalIF":3.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro assessment of anti-glioblastoma potential of Emblica officinalis methanolic fruit extract and green nanoparticles in U87-MG cells.","authors":"Kokkonda Jackson Sugunakara Chary, Anuradha Sharma, Amrita Singh","doi":"10.1007/s12032-025-03077-6","DOIUrl":"https://doi.org/10.1007/s12032-025-03077-6","url":null,"abstract":"<p><strong>Background: </strong>Plant-derived and other natural products are gaining attention due to wide therapeutic properties, specifically being looked for development of alternative therapeutic intervention for cancers. Phyllanthus emblica, also called Emblica officinalis, is well known for its abundance of phytochemicals and therapeutic uses since ancient times, and reports suggest its anticancer properties. However, no studies are conducted for brain cancers.</p><p><strong>Aim: </strong>The current study aims to evaluate the anti-brain cancer property of E. officinalis and to enhance the potency of selected extracts by development of green silver nanoparticles (AgNPs).</p><p><strong>Methodology and results: </strong>The Methanolic, Ethanolic, and Aqueous extracts of E. officinalis (M-EOE, E-EOE, and A-EOE) were obtained, followed by measuring total phenolic content and DPPH analysis. The results presented M-EOE with the highest presence of phenolic compounds, as supported by GC-MS. MTT assays showed dose-dependent antiproliferative potential of these extracts against U87-MG, where methanolic extract exhibited the lowest IC₅₀ value. Wound scratch assay further showed antimigratory potential, with lowest gap closure observed in methanolic extract. Further, methanolic extract of E. officinalis was used to synthesize AgNPs followed by characterization using particle-size analyzer, zeta potential, FTIR, and SEM-based analysis. Characterization methods revealed the synthesis of stable nanoparticles with size ranging from 52.56 to 96.18 nm. Further, these M-EOE AgNPs showed superior cytotoxicity, with an IC₅₀ value of 183.1 µg/mL, and antimigratory effects as compared to parent M-EOE extract.</p><p><strong>Conclusion: </strong>The current study thus suggests that E. officinalis extracts and derived nanoparticles may have the potential to be exploited as anti-brain cancer therapeutics and should be evaluated further by detailed mechanistic studies.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"516"},"PeriodicalIF":3.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in metallic nanostructure-based photothermal therapy in the management of cancer metastasis.","authors":"Rukaiah Fatma Begum, N Afreen, S Nirenjen, S Ankul Singh, Sudarshan Singh, Bhupendra G Prajapati","doi":"10.1007/s12032-025-03075-8","DOIUrl":"https://doi.org/10.1007/s12032-025-03075-8","url":null,"abstract":"<p><p>Metastatic cancer remains a leading cause of cancer-related mortality, demanding more precise and effective therapies. Photothermal therapy (PTT), a minimally invasive technique that employs light-induced heat to ablate tumors, has attracted attention for its ability to target malignant cells while sparing healthy tissue selectively. Incorporating metallic nanostructures, such as gold, silver, platinum, palladium, iridium, and metal oxides, has enhanced PTT efficacy through their unique optical and thermal properties, which enable efficient near-infrared absorption and heat conversion. Beyond hyperthermia, many metallic nanoparticles induce apoptosis, generate reactive oxygen species, and modulate mitochondrial function. Surface modification further improves their biocompatibility, tumor-specific targeting, and potential for drug delivery. These nanoplatforms also serve as versatile systems for combination therapies with chemotherapy, immunotherapy, or gene-based treatments. This review highlights recent progress in metallic nanostructure-mediated PTT, underlying mechanisms, and future challenges, underscoring its promise as a cornerstone in personalized management of metastatic cancers. Recent studies further demonstrate that PTT not only ablates primary tumors but also significantly reduces metastatic burden and prolongs survival in preclinical models. The inclusion of metallic nanostructures with high photothermal conversion efficiency, optimized laser parameters (wavelength, power, irradiation time), and controlled metal content provides a foundation for durable anti-metastatic outcomes and long-term therapeutic benefit.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"515"},"PeriodicalIF":3.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the crucial role of IGF2BP3 in modulating stemness traits of salivary adenoid cystic carcinoma.","authors":"Hongliang Xie, Lu Lu, Shiqin Wang, Li Feng, Bohan Li, Jianming Tang, Guoquan Zhang","doi":"10.1007/s12032-025-03068-7","DOIUrl":"10.1007/s12032-025-03068-7","url":null,"abstract":"<p><p>Salivary adenoid cystic carcinoma (SACC) is a rare yet clinically vexing malignancy characterized by perineural invasion, late lung-dominant metastasis, and limited systemic options, underscoring the need for mechanistic targets specific to SACC. This study employs a systematic experimental approach to elucidate the functional role and regulatory mechanisms of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in SACC cells. Initial validation confirmed elevated IGF2BP3 expression in SACC tumor tissue, with knockdown of IGF2BP3 markedly suppressing cell proliferation, clonogenicity, and migratory capacity in SACC cells. Subsequent RNA sequencing analysis revealed the downregulation of stemness pathways upon IGF2BP3 knockdown, corroborating its regulatory role in SACC stemness. Leveraging single-cell sequencing data, we corroborated the association between IGF2BP3 and stemness traits within SACC cells. In vivo experiments further demonstrated that IGF2BP3 knockdown attenuated SACC tumor growth. In summary, this study provides a comprehensive understanding of IGF2BP3's function and regulatory mechanisms in SACC, offering vital theoretical support for future targeted therapeutic strategies involving IGF2BP3.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"513"},"PeriodicalIF":3.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12518488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280561","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":"Photodynamic therapy boosts the anti-proliferative activity of oxaliplatin in cervical cancer cells by regulating stemness-related genes.","authors":"Shiva Lahouti, Mohammad Amin Doustvandi, AmirHossein Yari, Maryam Eslami, Sahar Safaei, Nadia Allahyarzadeh Khiabani, Behzad Baradaran","doi":"10.1007/s12032-025-03047-y","DOIUrl":"https://doi.org/10.1007/s12032-025-03047-y","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Cervical cancer is the fourth most prevalent cancer among women worldwide and remains a significant contributor to cancer-related mortality, particularly in low- and middle-income countries, largely due to treatment resistance and disease recurrence. Growing evidence indicates that cancer stem cells (CSCs) play a pivotal role in tumor initiation, progression, and therapeutic resistance. Consequently, the development of novel therapeutic strategies capable of eliminating cancer cells while simultaneously targeting CSC-associated pathways holds substantial clinical promise. This study aimed to evaluate the combined effects of zinc phthalocyanine-mediated photodynamic therapy (ZnPc-PDT) combined with oxaliplatin on cervical cancer cells. The focus was on assessing cell viability, apoptosis, colony formation, migration, stemness characteristics, and the expression of key genes involved in CSC regulation. Human cervical cancer cell lines (HeLa and Caski) were treated with ZnPc-PDT, oxaliplatin, or their combination. Cytotoxicity was measured using MTT assays, while apoptosis was evaluated by Annexin V/PI flow cytometry and expression profiling of apoptosis-related genes (CASPASE3, CASPASE8, CASPASE9, BCL2). Colony-forming assays were used to assess stemness potential, and wound-healing assays evaluated cell migration. Quantitative real-time PCR (qRT-PCR) was performed to examine the expression of stemness-related markers (SOX2, OCT4, CD133, CD44) and metastasis-associated genes (MMP2, MMP9, ROCK1). Additionally, in silico pathway analysis using TCGA-CESC, STRING, and Enrichr datasets identified oxaliplatin-targeted genes involved in CSC regulation and validated the experimental observations. Human cervical cancer cell lines (HeLa and Caski) were treated with ZnPc-PDT, oxaliplatin, or their combination. Cytotoxicity was measured using MTT assays, while apoptosis was evaluated by Annexin V/PI flow cytometry and expression profiling of apoptosis-related genes (CASPASE3, CASPASE8, CASPASE9, BCL2). Colony-forming assays were used to assess stemness potential, and wound-healing assays evaluated cell migration. Quantitative real-time PCR (qRT-PCR) was performed to examine the expression of stemness-related markers (SOX2, OCT4, CD133, CD44) and metastasis-associated genes (MMP2, MMP9, ROCK1). Additionally, in silico pathway analysis using TCGA-CESC, STRING, and Enrichr datasets identified oxaliplatin-targeted genes involved in CSC regulation and validated the experimental observations. The combination of ZnPc-PDT and oxaliplatin exhibits potent anti-cancer effects by inducing apoptosis, suppressing migration, reducing stemness, and modulating key cancer-related pathways. By integrating molecular experiments with in silico analysis, this study provides mechanistic insights into how PDT enhances oxaliplatin efficacy. These findings suggest that ZnPc-PDT combined with oxaliplatin may represent a promising therapeutic strategy to overcome drug resistance an","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"514"},"PeriodicalIF":3.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating DDIs in cancer patients receiving anticoagulants and antineoplastics: a scoping review focusing on therapeutic efficacy and safety.","authors":"Melina Yerolatsite, Nikolaos Tsoukalas, Grigoris Gerotziafas, Costas Pappas, Nanteznta Torounidou, Eleftheria Lefkou, Davide Mauri, Alexandros D Tselepis, Despoina Pantazi","doi":"10.1007/s12032-025-03074-9","DOIUrl":"https://doi.org/10.1007/s12032-025-03074-9","url":null,"abstract":"<p><p>Cancer-associated thrombosis (CAT) has become increasingly important due to its prevalence and impact on patient outcomes. The risk of venous thromboembolism (VTE) is significantly increased during cancer progression and cancer therapy, highlighting the urgent need for effective anticoagulant strategies. There are several categories of anticoagulants, the most important being low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs). Investigating drug-drug interactions (DDIs) of these anticoagulants with oncology drugs is crucial to ensure effective and safe treatment options for cancer patients. Using a comprehensive search strategy, the PubMed and Embase databases were used to identify studies reporting DDIs between anticoagulants and antineoplastic drugs through December 2023. Four studies met the inclusion criteria and included 299 patients, mostly women, with different comorbidities and treatment regimens for anti-thrombotic and anti-neoplastic therapy. Studies have reported varying degrees of severity of DDIs, ranging from no interaction to contraindicated interactions, which affect the efficacy and safety results of the treatment, such as bleeding and thrombotic events. Compared to DOACs, LMWHs does not interact with chemotherapy drugs. While LMWHs is preferred due to its predictable response and minimal toxicity, DOACs are a more appropriate option despite concerns regarding their interaction with oncological drugs. Understanding and managing DDIs between anticoagulant medications and oncology drugs is critical to optimising treatment outcomes for cancer patients. Further studies are needed to elucidate the clinical implications of these interactions and guide therapeutic decisions in this complex patient population.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"511"},"PeriodicalIF":3.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and transcriptomic alterations underlying aggressiveness in 5-fluorouracil-resistant HCT116 cells.","authors":"Pornchai Sooksaen, Arthid Thim-Uam, Ratsada Praphasawat, Chutamas Thepmalee, Kanokkarn Phromnoi, Damratsamon Surangkul, Surisak Prasarnpun, Chakkraphong Khonthun","doi":"10.1007/s12032-025-03078-5","DOIUrl":"https://doi.org/10.1007/s12032-025-03078-5","url":null,"abstract":"<p><p>Resistance to 5-fluorouracil (5-FU) remains an obstacle to effective colorectal cancer (CRC) treatment. Genetic alterations play significant roles in the development of drug-induced chemoresistance, leading to tumor recurrence and increased aggressiveness. This study sought to characterize the transcriptomic profiles of 5-FU-resistant CRC cells. HCT116 colon cancer cells were progressively exposed to increasing concentrations of 5-FU to induce resistance. Chemoresistance and aggressiveness were investigated using MTT, clonogenic, and scratch assays. Transcriptomic alterations were analyzed with next-generation sequencing (NGS). Our results revealed that 5-FU-resistant cells exhibited cross-resistance and enhanced invasive potential compared to parental HCT116 cells (HCT116-PT cells), characteristics that were associated with upregulation of matrix metalloproteinases (MMP-2 and MMP-9). Notably, we also observed significant overexpression of T cell immunoreceptor with Ig and ITIM domains (TIGIT) and cell adhesion-related genes, including neurexophilin and PC-esterase domain family member 1 (NXPE1) and neural cell adhesion molecule 1 (NCAM1). Non-coding RNAs such as microRNA-6789 (miR-6789), miR-5006, and miR-7107 were also upregulated. Pathway analysis suggested that enhanced cell survival, invasion, and apoptosis resistance in 5-FU-resistant cells may be due to the activation of several genes in the PI3K-AKT signaling pathway. In conclusion, our findings describe the transcriptomic features of chemoresistant CRC cells that are associated with aggressive tumor behavior. These insights may support the development of targeted therapies to overcome 5-FU resistance in CRC.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"512"},"PeriodicalIF":3.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}