Cancer research最新文献

{"title":"Abstract P22: Progestin (R5020) Induced Cell Apoptosis Via Mitochondria-Mediated Cell Death Pathway In MCF-7 Cell With PRB Overexpression","authors":"Qian Yee Woo, Pheck Khee Lau, Meng Wei, Shi Hao Lee, Kye Siong Leong, Natasa Bajalovic, Valerie C.L Lin","doi":"10.1158/1538-7445.fcs2024-p22","DOIUrl":"https://doi.org/10.1158/1538-7445.fcs2024-p22","url":null,"abstract":"Progestin has been widely reported to exert growth stimulatory or inhibitory effects on breast cancer cells depending on the cellular context. Our previous research showed that Promegestone (R5020) treatment induced apoptosis in MCF-7 cells with overexpression of PRB (MCF-7PRB), which paradoxically associated with massive downregulation of the known pro-apoptotic protein such as PARP, BID, Caspase 7 and 8. The objective of this study was to find out the mechanism of R5020-induced apoptosis in MCF-7PRB cells. Proteomic profiling of total cell lysates of control and R5020 treated MCF-7PRB cells were conducted using Tandem Mass Tag (TMT). HYPOXIA was found to be the topmost enriched Hallmark in R5020 treated cells. Western blotting analysis confirmed that HIF1A, BNIP3, and BNIP3L/NIX were massively upregulated in R5020 treated cells. BNIP3 and BNIP3L/NIX, the downstream apoptosis mediator of HIF1A can cause mitochondria dysfunction by forming pores on the mitochondria outer membrane or interacting with BCL-2 or BCL-xL. Indeed, mitotracker staining showed fragmented mitochondria, and this is associated with increased cytochrome C leakage into the cytoplasm and increased level of pro- and cleaved caspase 9 in R5020 treated cells. Furthermore, R5020 induced marked increases in many mitochondrial proteins including Apoptosis-Inducing Factor (AIF/AIFM1), AIFM2, Endonuclease G (EndoG), High Temperature Requirement A2 (HTRA2/ OMI), Second Mitochondria-Derived Activator of Caspases (Smac/DIABLO) and PARL (Presenilin-associated rhomboid-like), endonuclease G and Htra2/Omi, all of which are proapoptotic. For example, AIF/AIFM1and AIFM2 have been shown to induce caspase independent apoptosis by recruiting DNA nuclease such as ENGOG to the nuclease and causing chromatin condensation and DNA fragmentation. In conclusion, progestin induces mitochondria mediated apoptosis in breast cancer cells by activation of hypoxia pathway, upregulation of many proapoptotic mitochondrial proteins and downregulation of anti-apoptotic proteins BCL-2 and BCL-XL. Citation Format: Qian Yee Woo, Pheck Khee Lau, Meng Wei, Shi Hao Lee, Kye Siong Leong, Natasa Bajalovic, Valerie C.L Lin. Progestin (R5020) Induced Cell Apoptosis Via Mitochondria-Mediated Cell Death Pathway In MCF-7 Cell With PRB Overexpression [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl): nr P22.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"216 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P55: EVALUATION OF NON-PROGRAMMING VARIANT CALLERS FOR WHOLE-EXOME SEQUENCING USING GOLD STANDARD DATASETS","authors":"Matthew Wong, Bryan Liew, Melissa Hum, Ning Yuan Lee, Ann S. G. Lee","doi":"10.1158/1538-7445.fcs2024-p55","DOIUrl":"https://doi.org/10.1158/1538-7445.fcs2024-p55","url":null,"abstract":"Background: As whole-exome sequencing (WES) becomes more affordable and widely used, accurate variant calling is crucial for analysing WES data. Several commercial variant calling software have been developed that do not require bioinformatics or programming expertise. These software enable clinicians and scientists to independently analyse WES data and also support smaller laboratories and clinics in processing data without the need for costly computers or specialised staff. However, there is a noticeable lack of benchmarking studies to evaluate and compare the performance, quality and limitations of these software. Methods: To address this gap, we assessed the performance of four non-programming variant calling software: Illumina Basespace Sequence Hub – DRAGEN Enrichment (Illumina), CLC Genomics Workbench (CLC), Partek Flow (Partek), and Varsome Clinical (Varsome). Two different variant calling methods were performed on Partek: GATK and unionised Freebayes and Samtools (Partek F+S). Variant calling was performed using three Genome in a Bottle (GIAB) gold standard reference WES datasets. FASTQ data were aligned to the human reference genome GRCh38, and variants were assessed using the Variant Calling Assessment Tool (VCAT) against GIAB high-confidence regions. Results: Our findings reveal that Illumina's DRAGEN Enrichment outperformed others in single nucleotide variant (SNV) and insertion/deletion (indel) calling, achieving precision and recall scores over 99% for SNVs and 96% for indels. In contrast, Partek F+S exhibited the lowest performance in indel calling (73%). All four software shared 98 – 99% similarity for true positives variants called. The shortest run times ranged from 6 to 25 minutes for CLC and 29 to 36 minutes for Illumina, while Partek had the longest run time of 3.6 to 29.7 hours. Conclusion: This study provides important insights that will assist clinicians and scientists without programming expertise in selecting a suitable software for WES secondary variant analysis, balancing accuracy, sensitivity, and efficiency to meet specific research needs. Citation Format: Matthew Wong, Bryan Liew, Melissa Hum, Ning Yuan Lee, Ann S. G. Lee. EVALUATION OF NON-PROGRAMMING VARIANT CALLERS FOR WHOLE-EXOME SEQUENCING USING GOLD STANDARD DATASETS [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl): nr P55.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"29 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P76: Relative Expression of Transcripts Encoding Long and Short Isoforms of the PLAGL1 Zinc-Finger Protein Correlates with Progression and Prognosis in Colorectal Cancer: Evidence from Polish and TCGA Patient Cohorts","authors":"Bartlomiej E. Krazinski, Anna E. Kowalczyk, Marzena Mogielnicka-Brzozowska, Jacek Kiezun, Janusz Godlewski","doi":"10.1158/1538-7445.fcs2024-p76","DOIUrl":"https://doi.org/10.1158/1538-7445.fcs2024-p76","url":null,"abstract":"Background: PLAGL1 is a zinc-finger DNA-binding transcription factor with anti-proliferative properties. Genetic and epigenetic dysregulation of PLAGL1 has been implicated in the development and progression of various human cancers. The use of multiple alternative promoters and alternative splicing gives rise to numerous PLAGL1 transcript variants, resulting in two predominant protein isoforms: the longer isoform 2 and the shorter isoform 1. Alterations in the relative expression of PLAGL1 isoforms may represent a precise physiological regulatory mechanism that, when disrupted, could potentially contribute to various pathological processes. Our previous studies in the cohort of Polish patients with colorectal cancer (CRC) demonstrated decreased relative expression of PLAGL1 transcripts encoding isoform 2 in CRC tumors that correlated with the presence of distant metastases. Materials and Methods: In this study, we utilized data from The Cancer Genome Atlas (TCGA) cohort of CRC patients to (1) evaluate the prognostic significance of transcript variants encoding PLAGL1 isoforms, and (2) identify gene sets enriched in association with altered expression of PLAGL1 isoforms. Results: A reduced ratio of PLAGL1 isoform 2 to isoform 1 expression in CRC tumors was associated with advanced T-stage, perineural invasion, the presence of distant metastases, and worse prognosis. Bioinformatic analysis identified significant differences in gene set enrichment between CRC patients with low and high PLAGL1 isoform 2 to isoform 1 ratios. Conclusions: The results derived from TCGA datasets corroborate and extend our previous findings in the Polish cohort of CRC patients. Overall, these studies indicate that the relative expression of PLAGL1 isoforms may serve as a potential prognostic factor and therapeutic target in CRC. Acknowledgements: This research was funded by the Ministry of Science under “The Regional Initiative of Excellence Program” and the statutory grant of the School of Medicine, University of Warmia and Mazury in Olsztyn, Poland. Citation Format: Bartlomiej E. Krazinski, Anna E. Kowalczyk, Marzena Mogielnicka-Brzozowska, Jacek Kiezun, Janusz Godlewski. Relative Expression of Transcripts Encoding Long and Short Isoforms of the PLAGL1 Zinc-Finger Protein Correlates with Progression and Prognosis in Colorectal Cancer: Evidence from Polish and TCGA Patient Cohorts [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl): nr P76.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"6061 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P28: Synergistic Anti-Tumor Effects of Metastatic Ovarian Cancer on Combinatory Treatment with Chemotherapy and Metronomic CHI3L1-Specific Antibody Radionuclide","authors":"Chun-Tang Chen, Ming-Cheng Chang, Ping-Fang Chiang, Cheng-Liang Peng, Ying-Cheng Chiang","doi":"10.1158/1538-7445.fcs2024-p28","DOIUrl":"https://doi.org/10.1158/1538-7445.fcs2024-p28","url":null,"abstract":"Background: Radionuclide therapy is a well-established treatment to eradicate locally advanced cancer. Several radiopharmaceuticals have been applied to cancer therapy. Chitinase-3-like protein 1 (CHI3L1/YKL40) overexpression is highly correlated with poor outcomes in metastatic ovarian cancer and can be a promising target for targeted therapy. In this study, we report on metronomic CHI3L1-specific antibody radionuclide treatment combined with chemotherapy and evaluate their clinical applications for targeted therapy in metastatic ovarian cancer. Methods: The human ovarian cancer cell line CA5171 was used in vitro and in vivo studies. We investigated the therapeutic response of Lu-177-DTPA-YKL40 antibodies combined with paclitaxel or cisplatin in metastatic CA5171 tumor-bearing mice. We also evaluated the tumor volume, survival, histopathological examinations, and anti-tumor immune responses after treatments. Results: Tumor-bearing mice treated with low-dose Lu-177-DTPA-YKL40 antibodies (200 μCi/twice or 100 μCi/four times a week) and paclitaxel (6 mg/kg) or cisplatin (75 mg/m2) exhibited a dramatic increase in the infiltrated T cell and a significant reduction of tumor size. The combination of the CHI3L1-targeting antibody radionuclide and the chemotherapeutic agents, including paclitaxel and cisplatin, also elicited systematic effects on various subcutaneous, peritoneal-spread, and distant pulmonary metastatic tumors. Lu-177-DTPA-YKL40 antibodies also induce the cell death signal HMGB1 expression in apoptotic tumor cells and stimulate dendritic cell maturation, which results in inducing T cell activation. Conclusion: Combinatory treatment with chemotherapy and low-dose metronomic CHI3L1-specific antibody radionuclide treatment can enhance the anti-tumor effects on local and distant metastatic ovarian cancer. Tumor-specific antibody radionuclide combined with chemotherapy is a potential clinical new strategy for advanced cancer treatment. Citation Format: Chun-Tang Chen, Ming-Cheng Chang, Ping-Fang Chiang, Cheng-Liang Peng, Ying-Cheng Chiang. Synergistic Anti-Tumor Effects of Metastatic Ovarian Cancer on Combinatory Treatment with Chemotherapy and Metronomic CHI3L1-Specific Antibody Radionuclide [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl): nr P28.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"25 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Charting New Paths in Cancer Research: Insights from the Frontiers in Cancer Science Conference 2024.","authors":"Giang Le Minh, Sasidharan Swarnalatha Lucky, Shazib Pervaiz, Kristijan Ramadan, Joe Yeong, Sin Tiong Ong, Vaidehi Krishnan, Chit Fang Cheok, Wee Joo Chng, Sanjay De Mel, Xiaomeng Wang, Anand D Jeyasekharan, Chartsiam Tipgomut, Li Ren Kong, Kanaga Sabapathy, Cheng Ean Chee, Koji Itahana, Reshma Taneja, Soo-Chin Lee","doi":"10.1158/0008-5472.CAN-25-2205","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-25-2205","url":null,"abstract":"<p><p>The 16th annual Frontiers in Cancer Science conference convened leading experts to discuss the latest developments in cancer research. Key research themes included mechanisms of treatment resistance and innovative strategies to target resistant cancer cells, metabolic plasticity and its therapeutic vulnerabilities, modulation of the tumor microenvironment to enhance therapeutic efficacy, recent advances in immunotherapies and engineered immune cells, and strategies to overcome tumor immune evasion. The conference also highlighted the development of advanced spatial transcriptomic technologies as a powerful tool to decipher tumor heterogeneity and identify novel therapeutic targets. Additionally, the transformative potential of artificial intelligence and machine learning was explored in optimizing therapy selection, refining prognostication models, and improving patient outcomes, with a focus on advancing personalized, cost-effective cancer care. These collective insights underscore the rapid progress in the field and the potential for translating these discoveries into effective clinical interventions, marking a significant step toward addressing the complexities of cancer biology and enhancing patient care worldwide.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"85 15","pages":"2784-2787"},"PeriodicalIF":16.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P35: T cell monitoring and vaccine development platform (T-MoVac)","authors":"Wendy Lee, Olaf Rotzschke","doi":"10.1158/1538-7445.fcs2024-p35","DOIUrl":"https://doi.org/10.1158/1538-7445.fcs2024-p35","url":null,"abstract":"Recent success of Immune Checkpoint Blocker (ICB) revealed that (re-) activation of cancer-specific T cells is a key event in the induction of anti-tumour response. Vaccination of cancer patients with tumour antigens is thus a promising new way to engage the patient’s own immune system in potentially lifesaving anti-tumour response. Targets of this immune reaction are typically ‘neoantigens’. Neoantigens are present only in tumours and are formed by mutations that occur during tissue transformation. Due to random generation, each patient carries specific set of neoantigens. The T-MoVac program is a pipeline for the generation of personalized T cell vaccines comprising of functionally validated tumour antigens discovered and sourced from minimally invasive biopsies. It integrates Epitope discovery, Vaccine design, and T cell monitoring into a coherent pipeline to discover, develop and monitor new vaccines tailored specifically to the individual needs of the cancer patient. Citation Format: Wendy Lee and Olaf Rotzschke. T cell monitoring and vaccine development platform (T-MoVac) [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl): nr P35.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"18 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P08: INTERGRATING CELL SHAPE AND SPATIAL EXPRESSION IDENTIFIES MORPHOGENOMICS STATES IN LEUKEMIA","authors":"Jagadish Sankaran, Ignasius Joanito, Giovani Claresta Wijaya, Ziyue Chen, Joseph Lee, Vaidehi Krishnan, Than Hein, Shyam Prabhakar","doi":"10.1158/1538-7445.fcs2024-p08","DOIUrl":"https://doi.org/10.1158/1538-7445.fcs2024-p08","url":null,"abstract":"Spatial omics provides three types of information: location, gene expression, and morphology. While current algorithms typically integrate gene expression with location, they often overlook morphology. Chronic Myelomonocytic Leukemia (CMML) is a rare blood cancer characterized by sustained peripheral blood monocytosis, bone marrow dysplasia, and overlapping features of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). A higher level of monoblasts, which are an immature monocytes with round nuclei, is a known risk factor in CMML, but the underlying biology and markers remain unclear. In this study, we developed a novel framework that integrates gene expression and morphology to investigate morphogenomic phenotypes in 12 CMML patients and 8 healthy controls. Recognizing that most existing spatial omics workflows are designed for adherent cells and are unsuitable for suspension cells like bone marrow mononuclear cells (BMMC), we first developed a protocol for immobilizing suspension cells. This was followed by MERFISH spatial RNA analysis of 492 genes across approximately 25,000 cells in a 16 mm2 region of interest over 34 hours. We then introduced a Morphology and Expression Data Optimal Clustering (MEDOC) algorithm, which uses adaptive Fourier-domain alignment and graph clustering to analyze cell shapes. In healthy BMMC, MEDOC analysis identified genes correlated with cell shape, findings that were substantiated by single-cell RNA sequencing data, confirming their association with nuclear shape. Leveraging this shape marker, we successfully identified a promonocyte population, a monoblast subtype that was previously difficult to distinguish. Furthermore, MEDOC analysis in CMML patients revealed two distinct nuclear shapes in mature leukemic monocytes: one resembling a normal kidney bean shape and another characterized by dysmorphic features. Thus, our framework offers a powerful tool to uncover the underlying biology of clinically relevant malignant cell morphologies and to enhance CMML patient stratification. Citation Format: Jagadish Sankaran, Ignasius Joanito, Giovani Claresta Wijaya, Ziyue Chen, Joseph Lee, Vaidehi Krishnan, Than Hein, Shyam Prabhakar. INTERGRATING CELL SHAPE AND SPATIAL EXPRESSION IDENTIFIES MORPHOGENOMICS STATES IN LEUKEMIA [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl): nr P08.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"14 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P47: Harnessing Antineoplastic Properties of Artesunate for Prostate Cancer Therapy","authors":"Chandra Sekhar Bhol, Muthu Kumaraswamy Shanmugam, Grace Chew, Goh Si Rui Eva, Sujit Kumar Bhutia, Gautam Sethi","doi":"10.1158/1538-7445.fcs2024-p47","DOIUrl":"https://doi.org/10.1158/1538-7445.fcs2024-p47","url":null,"abstract":"Prostate cancer (PCa) is the most common cancer and a leading cause of cancer-related deaths among men globally, including in Singapore. The incidence of PCa has been increasing worldwide due to lifestyle changes, though there is a significant disparity in the incidence-to-mortality ratio between developed and developing countries, largely because of the advanced theragnostic approaches utilized in developed regions. While conventional treatments are effective for localized and metastatic PCa, treatment outcomes for metastatic castration-resistant prostate cancer (mCRPC), a more aggressive form of the disease, remain poor with current therapies failing to significantly extend survival. Hence, in the current study we investigated the potential role of artesunate (ART), a semisynthetic derivative of the malaria drug artemisinin in PCa cell lines. Interestingly, the ART found to inhibit the cell growth, invasion, migration, stemness and trigger the expression of apoptosis and autophagy-related proteins in PCa cell lines. In particular, ART inhibited the expression of Wnt/β-catenin pathway proteins responsible for the progression of prostate cancer to mCRPC. Moreover, inhibiting the ART induced autophagy resulted in the survival of the PCa cells to a greater extent. Furthermore, the ART treatment in a preclinical model of prostate cancer exhibited a significant reduction of prostate tumor growth along with the inhibition of lung and liver metastasis. Overall, our findings suggest that ART may activate a powerful antitumor mechanism, offering a new therapeutic approach for treating mCRPC. Citation Format: Chandra Sekhar Bhol, Muthu Kumaraswamy Shanmugam, Grace Chew, Goh Si Rui Eva, Sujit Kumar Bhutia, Gautam Sethi. Harnessing Antineoplastic Properties of Artesunate for Prostate Cancer Therapy [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl): nr P47.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"26 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P48: Oral Delivery of Bioorthogonal Catalytic Centres for Treating Gastric Cancer Using Gastrointestinal Tract Stabilized Thermostable Exoshells","authors":"Muthu Kumaraswamy Shanmugam, Girish Vallerinteavide Mavelli, Pang Yuze, Lik Hang Wu, Hrucha Shielesh Damle, Lim Poh Leong, Pakkiri Leroy Sivappiragasam, Chester Lee Drum","doi":"10.1158/1538-7445.fcs2024-p48","DOIUrl":"https://doi.org/10.1158/1538-7445.fcs2024-p48","url":null,"abstract":"Gastric cancer (GC) is the 5th most prevalent cancer worldwide. Current treatment methods are extremely challenging due to a variety of factors. Hence, targeted oral therapies that enable maximal drug release and absorption, while limiting potential systemic side effects are being explored. To materialize this, we introduce an oral disulfide-linked thermostable exoshell (DS-tES) system that delivers protein-based bioorthogonal catalytic centres directly to cancer tissues. DS-tES was effective at encapsulating and stabilizing labile catalytic centres such as horseradish peroxidase (HRP), preventing degradation in the harsh gastric environment. The enzymatic catalysis of the prodrug indole-3-acetic acid (IAA) produced active metabolites such as indole-3-carboxaldehyde in the presence of DS-tES encapsulated catalytic centres. In this study, we investigated the anti-cancer properties of DS-tES encapsulated HRP in combination with IAA. In vitro cell studies revealed dose and time dependent inhibition of gastric cancer cell growth, which was reversed in the presence of necrostatin-1 (nec-1), a RIPK1 inhibitor. The combination of DS-tES-HRP-IAA (DHI) elicited a time dependent induction of necroptosis. qPCR analysis revealed that DHI treatment upregulated necroptosis marker genes such as RIPK1, RIPK3 and MLKL. Furthermore, DHI treatment increased the mitochondrial membrane permeability transition and reactive oxygen species production. In an N-Methyl-N-Nitrosourea (MNU) induced gastric cancer mice model, oral administration of DHI significantly suppressed MNU induced tumor polyp growth in the stomach without any reduction in the mice body weight. Mass spectrometry-based quantifications revealed microgram amounts of the active metabolite in plasma from mice treated with DHI compared to control groups. In conclusion, we demonstrate that DHI is a unique inducer of necroptosis that inhibits tumor growth in vitro and in vivo. Citation Format: Muthu Kumaraswamy Shanmugam, Girish Vallerinteavide Mavelli, Pang Yuze, Lik Hang Wu, Hrucha Shielesh Damle, Lim Poh Leong, Pakkiri Leroy Sivappiragasam, and Chester Lee Drum. Oral Delivery of Bioorthogonal Catalytic Centres for Treating Gastric Cancer Using Gastrointestinal Tract Stabilized Thermostable Exoshells [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl): nr P48.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"14 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P12: Application of Novel Immune Signatures for the Early Detection of Colorectal Cancer","authors":"Yu Wang, Jinli Zhao, Heng Dong, Wei Wang, Yong Zeng, Jianxiang Chen","doi":"10.1158/1538-7445.fcs2024-p12","DOIUrl":"https://doi.org/10.1158/1538-7445.fcs2024-p12","url":null,"abstract":"Background &amp; Aims: Colorectal cancer (CRC) is one of the most common and deadly cancers worldwide. Here we aim to identify and develop novel diagnostic biomarkers to detect early-stage CRC. Methods: Candidate biomarkers were identified from RNA-seq, validated using RT-qPCR essays and developed through the bioinformatics pipeline using multivariate binary logistic regression and receiver operating characteristic curve analysis. Results: We identified a novel 2-gene signature within blood leukocytes which could robustly discriminate CRC from healthy controls (HC). Using an RT-qPCR assay based on the 2-gene signature, we detected CRC samples from HC samples with a sensitivity of 80% and a specificity of 81% in a training retrospective cohort of 314 samples and derived a logistic equation to calculate CRC risk probability termed as HIR-CRC. In an independent cohort of 178 samples, we validated 2-gene test and detected CRC from HC with a sensitivity of 82% and a specificity of 78%. Importantly, the 2-gene test can detect early-stage CRC and CRC which are tested negative for carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) with 76-88% sensitivity which is significantly higher than that of either CEA (31-56%) or CA19-9 (9-44%). Conclusion: The 2-gene signature described here can potentially fill an unmet clinical need for a robust screening assay to identify CRC patients at early stages when potentially curative treatment options are available. Citation Format: Yu Wang, Jinli Zhao, Heng Dong, Wei Wang, Yong Zeng, Jianxiang Chen. Application of Novel Immune Signatures for the Early Detection of Colorectal Cancer [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl): nr P12.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"25 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}