Recent patents on anti-cancer drug discovery最新文献

{"title":"Anisodine Activates SIK1 to Drive RIPK1-dependent Necroptosis in TNBC.","authors":"Zicheng Sun, Xiaoli Liang, Jiaming Xiao, Fan Bai, Yichen Tong, Xin Liu, Peng Hu, Mingwei Liang, Jiaqi Zhang, Andi Wan, Xiuhong Sun, Jie Li","doi":"10.2174/0115748928508182260928045722","DOIUrl":"https://doi.org/10.2174/0115748928508182260928045722","url":null,"abstract":"<p><strong>Introduction: </strong>Triple-Negative Breast Cancer (TNBC) has limited targeted therapeutic options. SIK1 is a tumor-suppressive kinase in breast cancer, but pharmacological SIK1 activators remain poorly defined. Although recent anticancer patents have disclosed SIK modulators and RIPK1/necroptosis-targeting agents, most SIK-related inventions focus on kinase inhibition rather than therapeutic SIK1 activation.</p><p><strong>Methods: </strong>We performed structure-based virtual screening of 23,006 traditional Chinese medicine- derived compounds against human SIK1 and validated anisodine binding and activity using molecular docking, CETSA, DARTS, immunoblotting, kinase assays, rescue experiments, RIPK1 mutagenesis, and xenograft models. Female BALB/c nude mice (4 weeks old) were used for the xenograft experiments.</p><p><strong>Results: </strong>Anisodine directly bound the SIK1 ligand-binding pocket, with S247 required for anisodine- mediated SIK1 activation. Anisodine increased pSIK1-T182 and SIK1 substrate phosphorylation, suppressed TNBC clonogenic growth and invasion, and reduced xenograft tumor growth. Pharmacological rescue showed that Necrostatin-1, but not inhibitors of apoptosis, ferroptosis, or copper chelation, reversed anisodine-induced cytotoxicity. Mechanistically, SIK1 interacted with RIPK1 and directly phosphorylated RIPK1 at Ser316, thereby activating the RIPK1(S316)-RIPK3-MLKL necroptosis cascade. RIPK1-S316A attenuated, whereas RIPK1- S316D enhanced, necroptotic signaling and tumor suppression.</p><p><strong>Discussion: </strong>These findings position anisodine as a mechanistically defined SIK1 activator and distinguish this strategy from existing SIK inhibitor-centered patent landscapes. The SIK1-RIPK1(S316) axis also provides a druggable framework that links kinase activation to regulated necroptosis in TNBC.</p><p><strong>Conclusion: </strong>This study identifies anisodine as a small-molecule SIK1 activator and defines a SIK1-RIPK1(S316) signaling axis that induces necroptosis in TNBC, supporting a patentrelevant therapeutic concept for kinase-directed and regulated-cell-death-based anticancer drug discovery.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carvacrol-enriched Multi-component Oil Reduces Tumour Growth in a Triple-negative Breast Cancer Xenograft Model.","authors":"Esra Küpeli, Didem Deliorman Orhan, Hakkı Tastan","doi":"10.2174/0115748928509831260914140853","DOIUrl":"https://doi.org/10.2174/0115748928509831260914140853","url":null,"abstract":"<p><strong>Introduction: </strong>Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with poor prognosis and limited targeted treatment options. Natural multicomponent formulations have emerged as promising complementary therapeutic approaches because of their ability to modulate multiple cancer-related pathways. To evaluate the antitumour efficacy and systemic effects of a carvacrol-enriched multi-component oil formulation (CMCO) in a xenograft mouse model of TNBC.</p><p><strong>Methods: </strong>CMCO was characterized using Gas Chromatography-Mass Spectrometry (GC-MS). BALB/c nude mice bearing MDA-MB-231 xenograft tumours were treated with CMCO orally (40 mg/kg) or by combined oral and topical administration for 40 days. Tumour progression was assessed histopathologically. Liver and kidney function tests, hematological parameters, and immune profiles were evaluated. Molecular mechanisms were investigated using real-time quantitative polymerase chain reaction targeting genes associated with apoptosis, autophagy, oxidative stress, and vesicular transport.</p><p><strong>Results: </strong>GC-MS analysis identified 30 phytochemical constituents, with carvacrol as the predominant compound. CMCO treatment reduced tumour cell density, improved stromal organization, and induced focal necrosis, particularly in the combined treatment group. Compared with cisplatin-treated animals, CMCO-treated mice exhibited a more favorable biochemical profile without evidence of hepatorenal toxicity. Gene expression analysis demonstrated upregulation of VPS29 and STK4 and modulation of CASP8, suggesting effects on apoptosis- and autophagy- related pathways.</p><p><strong>Discussion: </strong>Recent patent activity involving carvacrol-rich formulations, monoterpene-based phytotherapeutics, and essential oil-derived bioactive compositions highlights growing translational and commercial interest in natural-product-based therapeutic strategies. The present findings provide preclinical evidence supporting the potential applicability of standardized multicomponent phytotherapeutic formulations in TNBC management.</p><p><strong>Conclusion: </strong>CMCO demonstrated significant antitumour activity while maintaining a favorable safety profile in a TNBC xenograft model. These findings support further preclinical and clinical investigation of CMCO as a complementary therapeutic candidate for TNBC and contribute to the growing body of evidence supporting the development of natural-product-based anticancer formulations.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Kushenol</i> E Attenuates AOM/DSS-induced Colorectal Tumorigenesis in Mice, Inhibits Proliferation, and Induces Apoptosis in HT-29 Colorectal Cancer Cells.","authors":"Yan Wang, Zhe Ouyang, Yuan Man, Yao Wang, Zhenxi Sun, Ran Li, Heng Zhang, Luzhou Xu","doi":"10.2174/0115748928516880260914053850","DOIUrl":"https://doi.org/10.2174/0115748928516880260914053850","url":null,"abstract":"<p><strong>Introduction: </strong>Kushenol E is a prenylated flavonoid derived from Sophora flavescens. Although preliminary studies have suggested that Kushenol E possesses anticancer activity, its effects and molecular mechanisms in Colorectal Cancer (CRC) remain largely unexplored. Therefore, this study investigated the therapeutical effects of Kushenol E and its underlying molecular mechanisms against CRC.</p><p><strong>Methods: </strong>HT-29 cells, colorectal organoids, and an AOM/DSS-induced colorectal tumor model in mice were used. Cellular biomarkers related to growth, damage, programmed cell death, mitochondrial membrane integrity, and activation of the p38, ERK, and AKT signal cascades were measured. In vivo, survival rate, body weight, disease activity index, colon length, tumor volume, H&E staining, TUNEL assays, immunohistochemistry, and ELISA were assessed.</p><p><strong>Results: </strong>Kushenol E inhibited HT-29 cell proliferation, induced apoptosis, increased the expression of mitochondrial apoptosis-related proteins Bax and Caspase-3, and reduced Bcl-2 expression. Kushenol E also reduced phospho-ERK and phospho-AKT levels while increasing phospho-p38. In CRC organoids, Kushenol E significantly reduced organoid diameter on day 3 (p < 0.01) and decreased organoid viability (p < 0.01). In AOM/DSS-treated mice, Kushenol E showed increased TUNEL positivity and Bax and caspase-3 expression, together with reduced Ki67 and PCNA expression. Moreover, ELISA analysis showed that Kushenol E reduced serum levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and lowered the tumor-associated biomarker CEA.</p><p><strong>Discussion: </strong>Kushenol E inhibited CRC cell and organoid growth and attenuated AOM/DSSinduced colorectal tumorigenesis. These effects are associated with mitochondrial apoptosis and alterations in p38/ERK/AKT signaling, and are accompanied by reduced inflammatory cytokine and CEA levels in vivo.</p><p><strong>Conclusion: </strong>Kushenol E has shown excellent antitumor activity against CRC and warrants further mechanistic, pharmacological, and safety evaluation.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-derived Alkaloids as Emerging Therapeutic Agents for Colorectal Cancer: Molecular Mechanisms and Translational Perspectives.","authors":"Methiye Mancak, Esra Küpeli","doi":"10.2174/0115748928511781260901094143","DOIUrl":"https://doi.org/10.2174/0115748928511781260901094143","url":null,"abstract":"<p><strong>Introduction: </strong>Plant-derived alkaloids have attracted growing attention in Colorectal Cancer (CRC) research because of their diverse biological activities and ability to regulate multiple oncogenic pathways. CRC remains a major cause of cancer-related mortality worldwide despite advances in diagnosis and therapy.</p><p><strong>Methods: </strong>This review summarizes experimental and translational studies investigating the anticancer effects of plant-derived alkaloids in CRC, with emphasis on molecular mechanisms, cancer stem cell signaling, pharmacokinetic limitations, and recent patent-related developments.</p><p><strong>Results: </strong>Experimental studies have demonstrated that several alkaloids, including berberine, matrine, evodiamine, and palmatine, inhibit CRC progression through the induction of apoptosis, suppression of proliferation, inhibition of epithelial-mesenchymal transition, and modulation of inflammatory and oxidative stress-associated pathways. These compounds also influence signaling pathways frequently dysregulated in CRC, including Wnt/β-catenin, PI3K/Akt/mTOR, MAPK, NF-κB, and JAK/STAT signaling. Recent patents have focused on alkaloid-based formulations, nanotechnology-driven delivery systems, and combination strategies designed to improve therapeutic efficacy and bioavailability.</p><p><strong>Discussion: </strong>Although preclinical findings remain promising, most alkaloids investigated in CRC research continue to face limitations, including poor bioavailability, insufficient pharmacokinetic characterization, and limited clinical validation.</p><p><strong>Conclusion: </strong>Plant-derived alkaloids remain promising candidates for CRC therapy and chemoprevention. Further translational studies, pharmacological optimization, and clinically relevant investigations will be necessary to clarify their therapeutic applicability in CRC.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Therapeutics in Breast Cancer: Promise, Progress, and the Challenge of Triple-negative Subtype.","authors":"Shivam Sengupta, Ruhi Arisha, Kamal Shah, Hitesh Kumar Dewangan","doi":"10.2174/0115748928453880260827093711","DOIUrl":"https://doi.org/10.2174/0115748928453880260827093711","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer is the most common cancer that affects women globally, with several molecular subtypes defined by hormone and growth factor receptor expression. While advances in understanding the biology of these subtypes have led to targeted therapies, aggressive forms, particularly Triple-Negative Breast Cancer (TNBC), remain challenging due to their heterogeneity and lack of approved targeted options.</p><p><strong>Methods: </strong>This review explores current treatment approaches and emerging targeted therapies across the main breast cancer subtypes. We focus on the clinical development and translational potential of poly ADP-ribose polymerase (PARP) inhibitors, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, P13K/AKT/mTOR pathway inhibitors, histone deacetylase inhibitors, multi-target tyrosine kinase inhibitors, and immune checkpoint inhibitors.</p><p><strong>Results: </strong>Targeted therapies have significantly improved outcomes for patients with hormone receptor-positive and HER2-positive breast cancers, enhancing overall survival. TNBC, however, continues to pose a major challenge. Molecular subtyping offers a promising path to identify actionable targets and personalised treatment strategies. Across all subtypes, drug resistance, often driven by compensatory signalling pathways, remains a critical obstacle.</p><p><strong>Discussion: </strong>Precision medicine strategies, guided by detailed molecular profiling, are essential to optimise treatment effectiveness and overcome resistance. Thoughtfully designed combination therapies and adaptive clinical trials addressing resistance mechanisms hold great potential for improving patient outcomes.</p><p><strong>Conclusion: </strong>Advances in targeted and immune-based therapies are transforming breast cancer care. Leveraging molecular insights, particularly for TNBC, is crucial to delivering personalised, clinically meaningful treatments and improving outcomes across all subtypes.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring New Frontiers in Osteosarcoma Treatment: Clinical Trial Insights.","authors":"Ankit Sahoo, Majed Alrobaian, Faisal H Altemani, Omar Awad Alsaidan, Alhussain Aodah, Waleed H Almalki, Salem Salman Almujri, Faisal Alsenani, Jonathan A Lal, Mahfoozur Rahman","doi":"10.2174/0115748928447973260824065600","DOIUrl":"https://doi.org/10.2174/0115748928447973260824065600","url":null,"abstract":"<p><strong>Introduction: </strong>Osteosarcoma (OS) is a common bone malignancy in adolescents and older adults and typically develops in the long bones. Outcomes in advanced cases remain poor despite the use of chemotherapeutic drugs like doxorubicin, methotrexate, and cisplatin, underscoring the urgent need for safer, more focused treatments.</p><p><strong>Methods: </strong>A comprehensive review of clinical trials and literature identified emerging OS therapies targeting DNA repair, immune pathways, and tumor-specific markers. The EMA's approval of Mepact for nonmetastatic OS underscores the shift toward precision treatments and the evolving landscape of OS management. Patent protection can influence the pricing and accessibility of innovative medicines for OS by affecting market exclusivity and competition.</p><p><strong>Results: </strong>According to recent research, bone morphogenetic protein (BMP), RB, and TP53 gene alterations both contribute to the development of OS. These results highlight the importance of conducting further proteomic and genomic research in order to develop focused and efficient treatment plans. Furthermore, patent protection stimulates innovative drug development by encouraging research investment and faster launches, but restricts affordability due to exclusivity, posing a policy dilemma.</p><p><strong>Discussion: </strong>Treatment for OS is still challenging, particularly in high-grade and metastatic cases when conventional chemotherapy is frequently harmful and unsuccessful. While new targeted medicines and advances in understanding bone cell dynamics and genetic abnormalities such as TP53, RB, and BMPs offer hope for more accurate, less invasive treatments, the approval of Mapact represents progress.</p><p><strong>Conclusion: </strong>The necessity for integrated therapies combining immunotherapy, targeted delivery, and molecular insights to enhance OS treatment results is highlighted by developments in genomics and bone remodeling.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antineoplastic Drugs: Research Progress of Immune Checkpoint CD47 Inhibitors.","authors":"Liu-Liu Zhao, Rong-Rong Jin, Zhou Fang, Wen Zhang, Guo-Wu Rao, Quan Zheng","doi":"10.2174/0115748928447033260824144017","DOIUrl":"https://doi.org/10.2174/0115748928447033260824144017","url":null,"abstract":"<p><p>Immunotherapy using immune checkpoint inhibitors represents a breakthrough in cancer treatment. The overexpressed CD47 on tumor surfaces functions as a 'don't eat me' signal by binding to signal regulatory protein alpha (SIRPα) on macrophages, facilitating immune escape. However, the advancement of targeted CD47 inhibitors is currently challenged by uncertainties in efficacy, hematological safety, and dosing optimization. This paper provides a comprehensive overview of the structural domains and physiological functions of CD47. We evaluate the current research status of various inhibition strategies, including monoclonal antibodies, fusion proteins, bispecific antibodies, and small-molecule inhibitors, alongside their clinical combinations. The review further addresses developmental hurdles and highlights future prospects in utilizing this target for precision oncotherapy.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glypican-1 in Rhabdomyosarcoma: A Multi-omics Exploration of a Targetable Biomarker.","authors":"Belal Al-Zu'bi, Fatemah Ofo Alshammari, Randa AlQaisi, Jaber H Jaradat, A A Al-Abadleh, Rashed J Gousous, Abulmaaty M Elsayed, Yousef M Al-Saraireh, Mohammad Salem Hareedy","doi":"10.2174/0115748928472096260821102954","DOIUrl":"https://doi.org/10.2174/0115748928472096260821102954","url":null,"abstract":"<p><strong>Introduction: </strong>Glypican-1 (GPC1), a heparan sulfate proteoglycan found on the cell surface, has been associated with carcinogenesis and chemoresistance in several malignancies. However, its function in rhabdomyosarcoma remains poorly understood.</p><p><strong>Methods: </strong>GPC1 protein expression was evaluated in rhabdomyosarcoma tissue microarrays using immunohistochemistry and quantified using the Allred scoring system. Transcriptomic analysis was performed using the GSE108022 dataset, and protein-protein interaction networks were analyzed using STRING. Structural features were assessed using AlphaFold, and drug sensitivity associations were explored using CTRP data.</p><p><strong>Results: </strong>GPC1 protein expression was detected in 61.5% (64/104) of rhabdomyosarcoma cases, while 75% of normal skeletal muscle samples were negative. A significant association was observed between GPC1 expression and tumor subtype (p = 0.002, Cramér's V = 0.403), as well as sex (p = 0.025, Cra-mér's V = 0.219). Transcriptomic analysis showed significantly higher GPC1 expression in rhabdomyosarcoma compared to normal muscle (p < 0.001). Protein interaction analysis revealed enrichment in pathways related to cell adhesion, growth factor signaling, and extracellular matrix organization. Drug-sensitivity analysis indicated that higher GPC1 expression was associated with resistance to PI3K and HDAC inhibitors and increased sensitivity to vincristine, topotecan, and alisertib.</p><p><strong>Discussion: </strong>GPC1 is aberrantly expressed in rhabdomyosarcoma, influencing neoplastic signaling and treatment responses, and new patents emphasize its potential for therapeutic targeting and diagnostic purposes Conclusion: GPC1 is aberrantly overexpressed, readily accessible to ligands or other molecules, and is a functionally significant biomarker in rhabdomyosarcoma, with emerging potential for diagnostic purposes and targeted therapy development.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-target Drug Discovery for Cancer Therapy: A Contemporary Review.","authors":"Thirumalaikumaran Rathinam, S Pradeep Kumar Reddy, Yella Sirisha, Voleti Vijaya Kumar, Byran Gowramma, Dipen Purohit, Kaviarasan Lakshmanan","doi":"10.2174/0115748928462028260817063610","DOIUrl":"https://doi.org/10.2174/0115748928462028260817063610","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer remains one of the leading causes of mortality worldwide, with conventional therapies often limited by systemic toxicity, therapeutic resistance, and tumor heterogeneity. Multi-target drug discovery has emerged as a contemporary strategy to overcome these challenges, particularly through multi-kinase inhibitors and bispecific antibodies that simultaneously modulate multiple oncogenic pathways.</p><p><strong>Methods: </strong>This review integrates evidence from preclinical investigations, pivotal clinical trials, regulatory approvals, and key patent literature underpinning the development of multi-target anticancer agents. Representative multi-kinase inhibitors-including sorafenib, sunitinib, lenvatinib, cabozantinib, and regorafenib-are critically analyzed with respect to their molecular targets, therapeutic advantages, clinical performance, and associated intellectual property. Patented innovations covering kinase inhibition platforms, antibody engineering, and biomarkerbased cancer detection are also discussed.</p><p><strong>Results: </strong>MKIs act by concurrently inhibiting multiple signaling kinases, such as vascular endothelial growth factor receptors, platelet-derived growth factor receptors, fibroblast growth factor receptors, mesenchymal-epithelial transition factor, rearranged during transfection, and rapidly accelerated fibrosarcoma, thereby suppressing angiogenesis, limiting compensatory signaling, and addressing tumor heterogeneity. Clinical trials demonstrate significant survival benefits in hepatocellular carcinoma, renal cell carcinoma, and thyroid cancer. Parallel advances in patented bispecific antibodies and epigenetic diagnostic technologies further expand the therapeutic and diagnostic landscape.</p><p><strong>Discussion: </strong>Multi-targeting strategies delay resistance, reshape the tumor microenvironment, and improve outcomes, particularly when combined with immunotherapies or chemotherapies. However, challenges persist, including off-target toxicity, pharmacokinetic variability, high development costs, and limited accessibility. Patent trends reveal a growing emphasis on biomarker-guided patient selection, novel antibody formats, and rational combination therapies.</p><p><strong>Conclusion: </strong>MKIs and bispecific antibodies represent transformative modalities in modern oncology, supported by robust clinical evidence and extensive patent activity.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Halofuginone Affects the miR-34c-5p/MAP2K1 Axis Involved in the Development of Colorectal Cancer.","authors":"Yan-Yan Yan, Xin-Zhu Chen, Hong Bi, Jia-Bao Zhang, Li-Xin Han, Wei Zhang, Wen-Ying Zhu, Jian Wang, Zhuo-Fen Deng, Guo-Bin Zhang, Yu-Qing Wang, Jian-Ye Zhang","doi":"10.2174/0115748928447666260713094821","DOIUrl":"https://doi.org/10.2174/0115748928447666260713094821","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) is highly heterogeneous and develops due to the accumulation of genetic and epigenetic alterations. MicroRNAs (miRNAs) are involved in various aspects of CRC, such as epithelial-mesenchymal transition (EMT), proliferation, migration, and metastasis. However, the complex mechanisms involved remain incompletely understood. This study identifies CRC-related differentially expressed miRNAs (with a focus on miR- 34c-5p), verifies its target, and explores the regulatory mechanism of halofuginone (HF) in CRC via the miR-34c-5p/MAP2K1 axis.</p><p><strong>Methods: </strong>MiRNA sequencing (miRNA-Seq) identified differentially expressed miRNAs, which were verified by real-time quantitative PCR (RT-qPCR). miR-34c-5p expression was detected in HCT-15 cells and normal human primary colon epithelial cells; its effects on CRC cell proliferation, migration, and invasion were assessed in vitro and in vivo. Target prediction combined with dual-luciferase reporter assays validated the direct target of miR-34c-5p. Immunohistochemistry (IHC) was performed to analyse MAP2K1 expression in clinical samples and its correlation with the severity of precancerous lesions. The effect of HF on CRC via the miR-34c- 5p/MAP2K1 axis was examined in vitro and in vivo.</p><p><strong>Results: </strong>MiR-34c-5p was downregulated in HCT-15 cells compared with normal human primary colon epithelial cells and inhibited the malignant behaviours of CRC cells in vitro and in vivo. MAP2K1 was confirmed as the direct target of miR-34c-5p. MAP2K1 expression was positively correlated with the severity of colorectal precancerous lesions. HF suppressed CRC progression by regulating the miR-34c-5p/MAP2K1 axis in vitro and in vivo.</p><p><strong>Discussion: </strong>This study reveals that miR-34c-5p targets MAP2K1 to suppress colorectal cancer progression. HF upregulates miR-34c-5p and downregulates MAP2K1, exerting antitumour effects. The miR-34c-5p/MAP2K1 axis serves as a promising therapeutic target for CRC.</p><p><strong>Conclusion: </strong>Taken together, our study revealed that the miR-34c-5p/MAP2K1 axis is involved in the development and progression of human CRC and may provide novel insights into the prevention and treatment of CRC. This work also provides a brief overview of several recently issued patents.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}