Journal of the Egyptian National Cancer Institute最新文献

{"title":"Immune checkpoint crosstalk between LAG-3 and CD39/CD73 in glioblastoma: dual-pathway regulation of metabolic exhaustion and therapeutic reversal strategies.","authors":"Arpita Mukherjee","doi":"10.1186/s43046-026-00361-y","DOIUrl":"10.1186/s43046-026-00361-y","url":null,"abstract":"<p><p>Glioblastoma (GBM) represents an immunologically \"cold\" and metabolically suppressive tumor characterized by profound T-cell exhaustion, hypoxia-induced adenosinergic signaling, and resistance to checkpoint blockade. Converging evidence identifies lymphocyte-activation gene 3 (LAG-3) and the CD39/CD73 ectonucleotidase cascade as cooperative regulators of immune dysfunction within the GBM microenvironment. LAG-3 attenuates TCR/CD3 signaling and disrupts mitochondrial oxidative phosphorylation, diminishing effector T-cell persistence. Concurrently, CD39/CD73-mediated ATP hydrolysis elevates adenosine levels, activating A₂A receptors that inhibit glycolysis, suppress IFN-γ, and promote Treg and M2 macrophage polarization. Spatial and single-cell omics reveal co-localization of LAG-3⁺ exhausted T cells with CD73⁺ stromal and myeloid niches, suggesting a reciprocal immunometabolic feedback loop reinforcing exhaustion. This review elucidates the molecular crosstalk between LAG-3 signaling and the adenosine pathway, emphasizing key metabolic regulators including AMPK, mTOR, and HIF-1α. It further evaluates therapeutic strategies combining LAG-3 or PD-1 blockade with adenosine receptor antagonists or CD73 inhibitors to restore T-cell bioenergetics and antitumor activity. By integrating mechanistic immunometabolism with translational insights, this review establishes a dual-pathway framework of checkpoint synergy underlying resistance in GBM and proposes rational combination immunotherapies to reverse metabolic and immune exhaustion.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-vitro effects of the urotensin-II peptide and its receptor antagonists on mcf-7 breast cancer cell line.","authors":"Murat Olukman, Ezgi Olukman, Kutay Bulut, Burcu Bölük, Sunde Yılmaz Süslüer, Ayşe Erol","doi":"10.1186/s43046-026-00366-7","DOIUrl":"10.1186/s43046-026-00366-7","url":null,"abstract":"<p><strong>Background: </strong>Urotensin-II is a powerful vasoconstrictor peptide. Both the peptide and its receptor, GPR14, affect central nervous system, cardiovascular system, and kidney functions. Urotensin-II was found to be involved in the development of many solid organ tumors. The peptide and its receptor have been demonstrated to be present in breast cancer tissue. Moreover, its human plasma level is increased in breast cancer patients. It has also been reported that some cancer patients may have urotensin gene polymorphisms. Antagonists of this peptide receptor with different chemical structures have been produced and studied in different disease models. There are no experimental or clinical studies investigating the effects of urotensin-II receptor antagonists on breast cancer. In this study, MCF-7 cells were grown in an appropriate environment and then plated in wells. WST-8 was used to detect cell proliferation and inhibition effects. The expression levels of the MTA-1, ESR1, Kiss1, UT-II and UTR genes were measured via quantitative RT‒PCR. This study is the first to show the effects of urotensin-II peptide and its receptor antagonists on breast cancer.</p><p><strong>Results: </strong>While urotensin-II increased cell proliferation, all the antagonists had inhibitory effects. When the expression of genes affecting the metastasis or suppression of tumor cells was investigated, urotensin-II increased MTA-1 and ESR1 expression and decreased Kiss1 expression. Urotensin-II receptor antagonists reversed these effects.</p><p><strong>Conclusions: </strong>As a result, while urotensin-II triggered breast cancer cell proliferation, its receptor antagonists had inhibitory effects on proliferation and positive regulatory effects on tumor suppressor genes. These results suggest that urotensin-II receptor antagonists may provide effective results for breast cancer treatment.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of the microbiome in uterine cancer: insights into tumorigenesis, therapeutic implications, and clinical prospects.","authors":"Yating Zhang, Xiaochuan Yu, Li Shi, Chen Qi, Huali Wang","doi":"10.1186/s43046-026-00372-9","DOIUrl":"10.1186/s43046-026-00372-9","url":null,"abstract":"<p><p>Malignant tumors of the uterine cavity are a leading cause of cancer-related mortality in women worldwide. In recent years, the tumor microenvironment, as a novel biological concept, has garnered increasing attention. The microenvironment plays a crucial role in the initiation, progression, and response to treatment of tumors. Although research on the microenvironment of malignant uterine tumors is in its early stages, preliminary findings suggest that alterations in the microbial communities of cervical and endometrial cancers are closely associated with tumorigenesis, immune evasion, metastasis, and treatment resistance. Notably, specific microbial community changes have potential diagnostic and prognostic implications, offering novel insights into the management of these cancers.This review aims to summarize and analyze the current state of research on the microenvironment of malignant uterine tumors, particularly its role in cervical and endometrial cancers. We first overview the epidemiological landscape and microenvironmental features of these tumors, emphasizing how microbial communities influence tumor initiation and progression. This influence occurs through immune modulation, metabolic changes, and alterations within the tumor microenvironment. Second, the potential role of the microenvironment in tumor therapy is explored, particularly its application prospects in chemotherapy, radiotherapy, and immunotherapy. In addition, the application potential of microbial communities in early tumor diagnosis, efficacy monitoring, and prognosis assessment is discussed.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148226441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholecystectomy-associated gut microbiota dysbiosis promotes colorectal carcinogenesis: from epidemiological controversy to FXR-centered mechanistic insights.","authors":"Zhongqin Huang","doi":"10.1186/s43046-026-00360-z","DOIUrl":"10.1186/s43046-026-00360-z","url":null,"abstract":"<p><strong>Background and objective: </strong>Cholecystectomy is one of the most common surgeries worldwide, yet its association with colorectal cancer (CRC) risk remains controversial. Recent advances have linked gut microbiota and bile acid alterations to this risk. This review synthesizes epidemiological evidence and molecular mechanisms, focusing on the microbiota-bile acid-FXR signaling axis, and proposes a personalized prevention framework. Epidemiological data reveal consistent patterns: proximal colon cancer predominance, higher risk in women, and peak incidence 5-15 years post-surgery. Cholecystectomy induces gut microbiota dysbiosis (decreased Bifidobacterium breve, increased Ruminococcus gnavus) and bile acid disturbances (elevated TUDCA/GUDCA, altered protective bile acids), which converge on FXR signaling.</p><p><strong>Core findings: </strong>The FXR signaling axis is a central hub. Yang et al. (Nat Commun 2025) showed that cholecystectomy-induced microbiota shifts alter bile acids, suppress FXR, disrupt FXR/β-catenin interaction, and promote tumorigenesis. The FXR agonist obeticholic acid prevents these effects preclinically, but systemic toxicity limits clinical use.</p><p><strong>Conclusion and significance: </strong>We propose personalized risk stratification integrating demographics, microbial signatures, and metabolic biomarkers. Interventions include gut-restricted FXR agonists, probiotics, and Mediterranean diet. Future directions include prospective validation and dynamic network modeling.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiosensitizing effect of astaxanthin on radiation-induced cytotoxicity in breast cancer cells.","authors":"Bothaina Al-Awady, Abdel-Moneim Osman, Diana Hanna, Shereen El Kiki, Ebtehal El-Demerdash, Marwa Sharaky","doi":"10.1186/s43046-026-00352-z","DOIUrl":"10.1186/s43046-026-00352-z","url":null,"abstract":"<p><p>BACKGROUND: Radiotherapy (RT) is a primary treatment for cancer, including breast cancer, but its effectiveness is limited by severe side effects. Radiosensitization using natural products can enhance efficacy while reducing radiation doses. Astaxanthin (AST), a natural carotenoid with antioxidant properties, requires further investigation for its role in cancer therapy. Especially in many previous studies, AST found to has prooxidant effect in cancer cells reverse its antioxidant effect in normal cells. METHODS: This study explored AST’s potential to enhance the cytotoxic effects of ionizing radiation (IRR) against MCF7 breast cancer cells and the underlying mechanisms. Cytotoxicity, apoptosis induction, anti-metastatic activity, and cell cycle distribution were analyzed in response to IRR with and without AST. RESULTS: IRR alone showed limited cytotoxicity, whereas addition of AST significantly enhanced IRR’s effects, reducing IC50 by ten folds in combination treatment. AST increased apoptosis markers (caspase-3 and BAX/BCL2 ratio) by 16% and 67.8%, respectively. It also decreased proliferation index and S-phase ratio by 43.24% and 42.6%, respectively. AST further reduced metastatic markers MMP2 and MMP9 by 25% and 33.8%, respectively, in combination therapy. Additionally, AST exhibited a pro-oxidant effect, elevating MDA and H₂O₂ levels by 16.9% and 18.9%, respectively. It also caused cell cycle arrest at the S and G2/M phases, making cells more susceptible to IRR. CONCLUSION: These findings confirm AST’s radiosensitizing effect via apoptosis induction, cell cycle disruption, and anti-metastatic activity, supporting its potential in enhancing radiotherapy efficacy for breast cancer cells. Further research is warranted to explore its application in cancer treatment. </p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A real-world study of the effectiveness and safety of low-dose immunotherapy in addition to oral metronomic chemotherapy in recurrent and metastatic head and neck squamous cell carcinoma.","authors":"Rushabh Kothari, Avinash Khadela, Gaurang Modi, Itesh Khatwani, Palak Bhatt, Vaishnavi Patel, Vraj B Shah","doi":"10.1186/s43046-026-00356-9","DOIUrl":"10.1186/s43046-026-00356-9","url":null,"abstract":"<p><p>BACKGROUND: The standard of care in recurrent/metastatic head and neck squamous cell carcinoma is Pembrolizumab with/without chemotherapy. However, these regimens are minimally affordable and accessible in resource-limited countries. Hence, immunotherapy is combined with oral metronomic chemotherapy in lower doses. Currently, the efficacy and safety of this regimen have been studied in platinum-refractory settings and not beyond them. Thus, we conducted a real-world study on the effectiveness of low-dose immunotherapy and metronomic chemotherapy in recurrent/metastatic head and neck cancer. METHODOLOGY: This was a multicentre, real-world, prospective observational study. Recurrent/metastatic head and neck squamous cell carcinoma patients treated with palliative intent with an Eastern Cooperative Oncology Group performance status of 0–2 were recruited from three oncology centres. Patients received oral metronomic chemotherapy with IV nivolumab 20 mg once every 3 weeks. Patients received treatment until disease progression or unacceptable toxicities. The primary endpoints were Objective response rate, progression-free survival, and Overall survival. The secondary endpoint was safety. Moreover, subgroup analysis was also carried out among platinum sensitivity and the line of treatment. RESULTS: Overall, 123 patients were recruited (86% males and 35% females). The Objective response rate was 61.7% (95% CI, 53 to 70). The median overall survival and progression-free survival were 15.1 months (95% CI, 12.8–17.4) and 10.4 months (95% CI, 8.0-13.7), respectively. Moreover, the median overall survival was 15.9 (95% CI, 12.7 to 17.5) versus 8.0 months (95% CI, 3.4–12.6) (p < 0.01) and the median progression-free survival were 13.6 months (95% CI, 9.9–17.2) versus 5.0 months (95% CI, 2.2–7.8) (p < 0.01) for platinum sensitive and resistant subgroups respectively. The median OS were 15.1 months (95% CI, 12.7–17.5) versus 8.0 months (3.4–12.6) (p = 0.03), and the median PFS were 11.2 months (95% CI, 6.3–16.0) versus 6.0 months (95% CI, 2.7–9.3) (p = 0.07) for first and second-line subgroups, respectively. The most common adverse events were fatigue (63.4%), anemia (52.8%), mucositis (47.9%), and rashes (44.7%). CONCLUSION: This study demonstrated that adding low-dose immunotherapy to oral metronomic chemotherapy was effectively applicable and associated with manageable toxicities in a real-world setting for the management of R/M HNSCC. Furthermore, this regimen was associated with favourable survival outcomes and response rates in the platinum-sensitive and first-line treatment subgroups. </p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The non-bacterial oncobiome: the role of the mycobiome and virome in tumor plasticity.","authors":"Isaac Johnson Ajeh, Ozhe Sunday Isaac Ikukpla'si","doi":"10.1186/s43046-026-00370-x","DOIUrl":"10.1186/s43046-026-00370-x","url":null,"abstract":"<p><p>Tumor plasticity, the capacity of malignant cells to undergo reversible phenotypic switching, is a fundamental driver of lineage diversion and therapeutic resistance. While the bacterial microbiome is a recognized modulator of the tumor microenvironment (TME), the non-bacterial oncobiome, comprising the mycobiome (fungi) and virome (viruses), represents a critical but under-explored frontier in cellular adaptability. This review synthesizes current evidence regarding the mechanistic contributions of fungal and viral constituents to tumor plasticity and characterizes the molecular cross-talk that facilitates host cell reprogramming. We conducted a structured narrative synthesis of literature indexed in PubMed, Scopus, and Web of Science (2020-2026), focusing on high-throughput studies such as ITS sequencing, metagenomics NGS (mNGS), and single-cell network analyses. We specifically evaluated evidence concerning the activation of host pattern recognition receptors and the subsequent transcriptional rewiring of lineage-defining markers. Emerging data indicate that fungal dysbiosis, particularly involving Candida and Malassezia species, triggers the Dectin-1/STAT3 signaling axis, a known inducer of epithelial-mesenchymal transition (EMT). Concurrently, the virome, ranging from integrated oncoviruses to reactivated endogenous retroviruses (ERVs), is shown to hijack the Wnt/ β-catenin pathway, enforcing a progenitor-like stemness state. This inter-kingdom synergy promotes an immune-excluded niche, effectively shielding plastic sub-populations from cytotoxic stress and targeted therapies. The non-bacterial oncobiome provides genomic momentum and inflammatory cues necessary to lower the threshold for phenotypic switching. This review highlights that stabilizing the TME ecosystem through ecologically targeted therapy may be a prerequisite for overcoming drug resistance and improving clinical outcomes in refractory cancers.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence in cancer immunotherapy: current trends in predicting response and personalizing treatment.","authors":"Eloghosa Aisosa Nosa-Ihaza, Emmanuel Chidera Edeh, Wol Bol Geng, Ebenezer Okenwa","doi":"10.1186/s43046-026-00371-w","DOIUrl":"10.1186/s43046-026-00371-w","url":null,"abstract":"<p><p>Artificial intelligence (AI) can transform cancer immunotherapy by enabling more accurate prediction of treatment responses, the discovery of specific biomarkers, and the development of personalised treatment plans. Traditional single-marker biomarkers (PD-L1, TMB, MSI) lack consistency across tumour types and cannot be used to assess tumour heterogeneity or the dynamic tumour microenvironment (TME). This review synthesises developments in multimodal AI models that combine genomics, transcriptomics, radiomics, digital pathology (pathomics), circulating biomarkers, and clinical evidence to create composite predictive signatures with significantly better discriminatory value. AUCs over 0.8 have been seen in a few retrospective studies with deep learning and ensemble models on whole-slide images, CT/MRI/PET radiomics, spatial and single-cell omics, and multi-omics fusion models, but prospective and multicentre validation is scarce, and external validation often shows deterioration in performance. AI is also used to enhance the translational pipelines of adoptive cell therapies (e.g., CAR-T) by improving patient selection, manufacturing (e.g., digital twins), and early toxicity prediction (e.g., CRS, ICANS). Nevertheless, clinical implementation remains hindered by data heterogeneity, bias, poor longitudinal validation, limited reproducibility, and a lack of transparency in most models, even though prospective, multicenter validation and explainable AI are crucial for clinician trust and regulatory acceptance. New systems such as federated learning, foundation models, spatial omics, digital twins, and wearable monitoring represent paths to generalizable, privacy-preserving, and actionable systems in clinical practice. To achieve the potential of AI, the generation of data will need to be standardized, reporting must be transparent, interdisciplinary, and regulatory frameworks must be strengthened focusing on the practical use of AI and patient safety. By taking these steps, AI could be shifted to prospective clinical decision support, which uses AI to meaningfully enhance personalization and outcomes in cancer immunotherapy based on a retrospective research tool.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The additive value of 3D automated breast ultrasound and contrast enhanced spectral mammography in the assessment of suspicious breast lesions.","authors":"Lamiaa Hassan ELmalatawy, Noha Abd El-Shafy Elsaid","doi":"10.1186/s43046-026-00357-8","DOIUrl":"10.1186/s43046-026-00357-8","url":null,"abstract":"<p><strong>Background: </strong>Worldwide, breast cancer is the most commonly diagnosed cancer among women accounting for over a million cases each year. Mammography still remains the gold standard for early detection of breast cancer. Contrast Enhanced Spectral Mammography (CESM) allows better estimation of the lesion size and detection of multifocal breast cancers. Automated breast ultrasound (ABUS) is an innovation of breast ultrasound that attains 3-D images of the entire breast overcoming the limitations of hand-held ultrasound. The aim is to evaluate the impact of 3D ABUS in correlation with CESM on the characterization and assessment of disease extent.</p><p><strong>Design & population: </strong>The study was performed at the Female Imaging Unit of the National Cancer Institute (NCI), Cairo University and in Baheya Foundation. One hundred and six patients were randomly chosen out of patients who were initially given BIRADS IV - V by standard mammography. The contrast enhanced digital mammography and 3D automated ultrasound data were evaluated by two experienced radiologists; both observers were blinded to the pathological data of each patient.</p><p><strong>Results: </strong>Regarding primary outcome of our study in assessment of tumor size, extension and multiplicity, the use of ABUS after CESM showed significant increase in the sensitivity of the test (80% for combined test versus 40% for CESM alone), while it showed almost no significant difference in specificity (70% for CESM and Combined tests).The ABUS also showed more accuracy in detection of suspicious lesions (61%) than the CESM (40%.) CONCLUSION: ABUS is considered a revolution in breast scanning by ultrasound imaging that can be used as a non-invasive complementary tool to CESM in assessment of suspicious breast lesions showing increased accuracy of study and patient outcome upon combing both of them.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148032243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-145 restoration overcomes oxaliplatin resistance via ABCC1 in colorectal cancer.","authors":"Mahsa Sadeghzadeh, Milad Asadi, Behzad Baradaran, Venus Zafari, Soghra Bornehdeli, Haniye Mohammad Reza Khani, Behzad Mansoori, Habib Zarredar, Dariush Shanehbandi","doi":"10.1186/s43046-026-00349-8","DOIUrl":"10.1186/s43046-026-00349-8","url":null,"abstract":"<p><p>BACKGROUND: Drug resistance limits effectiveness of chemotherapy in colorectal cancer (CRC). Consequently, finding appropriate strategies for re-sensitizing chemo-resistant cells is crucial. Our present study aimed at taking advantage of chemotherapy and gene therapy by restoring microRNA-145 expression in oxaliplatin resistant CRC cells. METHODS: Bioinformatic analysis of clinical CRC datasets demonstrated significantly reduced miR-145 expression in tumor tissues compared with normal samples. Oxaliplatin-resistant SW-480 cells were generated and transfected with a pCMV-miR-145 expression vector. The MTT assay was used to assess cell viability following miR-145 restoration, oxaliplatin treatment, or their combination. Apoptosis was measured via flow cytometry. Gene expression levels of ABCC1, MDR1, K-RAS, MMP-13, Bcl-2, CASP3, CASP8, and CASP9 were analyzed using qRT-PCR, and ABCC1 protein expression was evaluated by western blotting. Cell migration was assessed using a wound-healing assay. RESULTS: Co-treatment with miR-145 and Oxaliplatin significantly reduced cell viability, proliferation, and migration and increased apoptosis compared to the either treatments. Restoring miR-145 expression downregulated reduced the drug-resistance genes ABCC1 and MDR1, and reduced decreased expression of oncogenes including K-RAS and Bcl-2, while increasing expression of apoptosis-related genes (CASP3, CASP8, and CASP9). CONCLUSION: miR-145 restoration via decreasing the drug resistance biomarkers ABBCC1 and MDR1, along with other oncogenes like K-Ras and Bcl2, and increasing apoptosis conductors could sensitize oxaliplatin-resistant cells to chemotherapy. This proposes a novel and clinically translatable strategy to control drug resistance in CRC, finding new ways to increasing chemotherapeutic efficacy. </p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}