Home / Journals / OR / Vol.31, No.4, 2023
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  • Open AccessOpen Access

    REVIEW

    Targeting DNA repair for cancer treatment: Lessons from PARP inhibitor trials

    DHANYA K. NAMBIAR1, DEEPALI MISHRA2, RANA P. SINGH2,3,*
    Oncology Research, Vol.31, No.4, pp. 405-421, 2023, DOI:10.32604/or.2023.028310
    Abstract Ionizing radiation is frequently used to treat solid tumors, as it causes DNA damage and kill cancer cells. However, damaged DNA is repaired involving poly-(ADP-ribose) polymerase-1 (PARP-1) causing resistance to radiation therapy. Thus, PARP-1 represents an important target in multiple cancer types, including prostate cancer. PARP is a nuclear enzyme essential for single-strand DNA breaks repair. Inhibiting PARP-1 is lethal in a wide range of cancer cells that lack the homologous recombination repair (HR) pathway. This article provides a concise and simplified overview of the development of PARP inhibitors in the laboratory and their clinical More >

    Graphic Abstract

    Targeting DNA repair for cancer treatment: Lessons from PARP inhibitor trials

  • Open AccessOpen Access

    REVIEW

    Scaffold proteins of cancer signaling networks: The paradigm of FK506 binding protein 51 (FKBP51) supporting tumor intrinsic properties and immune escape

    LAURA MARRONE1, MASSIMO D’AGOSTINO1, CAROLINA GIORDANO2, VALERIA DI GIACOMO1, SIMONA URZINI1, CHIARA MALASOMMA1, MARIA PAOLA GAMMELLA1, MARTINA TUFANO1, SIMONA ROMANO1,*, MARIA FIAMMETTA ROMANO1,*
    Oncology Research, Vol.31, No.4, pp. 423-436, 2023, DOI:10.32604/or.2023.028392
    Abstract Scaffold proteins are crucial regulators of signaling networks, and their abnormal expression may favor the development of tumors. Among the scaffold proteins, immunophilin covers a unique role as ‘protein-philin’ (Greek ‘philin’ = friend) that interacts with proteins to guide their proper assembly. The growing list of human syndromes associated with the immunophilin defect underscores the biological relevance of these proteins that are largely opportunistically exploited by cancer cells to support and enable the tumor’s intrinsic properties. Among the members of the immunophilin family, the FKBP5 gene was the only one identified to have a splicing variant. More >

    Graphic Abstract

    Scaffold proteins of cancer signaling networks: The paradigm of FK506 binding protein 51 (FKBP51) supporting tumor intrinsic properties and immune escape

  • Open AccessOpen Access

    REVIEW

    Tumor neoantigens: Novel strategies for application of cancer immunotherapy

    HANYANG GUAN1,#, YUE WU2,#, LU LI3,#, YABING YANG1, SHENGHUI QIU1, ZHAN ZHAO1, XIAODONG CHU1, JIASHUAI HE1, ZUYANG CHEN1, YIRAN ZHANG1, HUI DING1, JINGHUA PAN1,*, YUNLONG PAN1,*
    Oncology Research, Vol.31, No.4, pp. 437-448, 2023, DOI:10.32604/or.2023.029924
    Abstract Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer. The recognition of antigens by immune cells is a crucial step in tumor-specific killing, and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells, making them an attractive therapeutic target. Currently, neoantigens find utility in various domains, primarily in the realm of neoantigen vaccines such as DC vaccines, nucleic acid vaccines, and synthetic long peptide vaccines. Additionally, they hold promise in adoptive cell therapy, encompassing tumor-infiltrating cells, T cell receptors, and chimeric antigen More >

    Graphic Abstract

    Tumor neoantigens: Novel strategies for application of cancer immunotherapy

  • Open AccessOpen Access

    REVIEW

    Underlying mechanisms and clinical potential of circRNAs in glioblastoma

    LEI ZHANG*, YUAN ZHANG, HUIJUAN GAO, XIN LI, PEIFENG LI*
    Oncology Research, Vol.31, No.4, pp. 449-462, 2023, DOI:10.32604/or.2023.029062
    Abstract Glioblastoma (GBM) is the most malignant form of glioma and is difficult to diagnose, leading to high mortality rates. Circular RNAs (circRNAs) are noncoding RNAs with a covalently closed loop structure. CircRNAs are involved in various pathological processes and have been revealed to be important regulators of GBM pathogenesis. CircRNAs exert their biological effects by 4 different mechanisms: serving as sponges of microRNAs (miRNAs), serving as sponges of RNA binding proteins (RBPs), modulating parental gene transcription, and encoding functional proteins. Among the 4 mechanisms, sponging miRNAs is predominant. Their good stability, broad distribution and high More >

    Graphic Abstract

    Underlying mechanisms and clinical potential of circRNAs in glioblastoma

  • Open AccessOpen Access

    ARTICLE

    Targeting LncRNA LLNLR-299G3.1 with antisense oligonucleotide inhibits malignancy of esophageal squamous cell carcinoma cells in vitro and in vivo

    LI TIAN1,#, YONGYI HUANG1,#, BAOZHEN ZHANG2,#, YI SONG1,#, LIN YANG3, QIANQIAN CHEN1, ZHENG WANG3, YILING WANG1, QIHAN HE1, WENHAN YANG1, SHUYONG YU4, TIANYU LU5, ZICHEN LIU1, KAIPING GAO1,*, XIUJUN FAN2,*, JIAN SONG4,*, RIHONG ZHAI1,*
    Oncology Research, Vol.31, No.4, pp. 463-479, 2023, DOI:10.32604/or.2023.028791
    Abstract Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) play critical roles in the development and progression of cancers, including esophageal squamous cell carcinoma (ESCC). However, the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge. By RNA-sequencing analysis, we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA. LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion. Silencing of LLNLR-299G3.1 with ASO (antisense oligonucleotide) resulted in opposite effects. Mechanistically, LLNLR-299G3.1 bound to cancer-associated RNA binding proteins and regulated the expression… More >

  • Open AccessOpen Access

    ARTICLE

    LAMC2 regulates proliferation, migration, and invasion mediated by the Pl3K/AKT/mTOR pathway in oral squamous carcinoma

    FAYU SHAN1, LANLAN LIANG1, CHONG FENG1, HONGBAO XU1, ZIROU WANG1, WEILI LIU1, LINGLING PU1, ZHAOLI CHEN1, GANG CHEN2,*, XINXING WANG1,*
    Oncology Research, Vol.31, No.4, pp. 481-493, 2023, DOI:10.32604/or.2023.029064
    Abstract Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor. Recently, Laminin Gamma 2 (LAMC2) has been shown to be abnormally expressed in OSCC; however, how LAMC2 signaling contributes to the occurrence and development of OSCC and the role of autophagy in OSCC has not been fully explored. This study aimed to analyze the role and mechanism of LAMC2 signaling in OSCC and the involvement of autophagy in OSCC. Methods: To explore the mechanism by which LAMC2 is highly expressed in OSCC, we used small interfering RNA (siRNA) to knock down LAMC2 to further… More >

  • Open AccessOpen Access

    ARTICLE

    mTORC2 promotes pancreatic cancer progression and parp inhibitor resistance

    CHIWEN BU1,2, LIGANG ZHAO1, LISHAN WANG1, ZEQIAN YU1, JIAHUA ZHOU1,*
    Oncology Research, Vol.31, No.4, pp. 495-503, 2023, DOI:10.32604/or.2023.029309
    Abstract Pancreatic cancer is one of the most aggressive cancers with a median survival time of less than 5 months, and conventional chemotherapeutics are the main treatment strategy. Poly(ADP-ribose) polymerase (PARP) inhibitors have been recently approved for BRCA1/2-mutant pancreatic cancer, opening a new era for targeted therapy for this disease. However, most pancreatic cancer patients carry wild-type BRCA1/2 with resistance to PARP inhibitors. Here, we reported that mammalian target of rapamycin complex 2 (mTORC2) kinase is overexpressed in pancreatic cancer tissues and promotes pancreatic cancer cell growth and invasion. Moreover, we found that knockdown of the More >

    Graphic Abstract

    mTORC2 promotes pancreatic cancer progression and parp inhibitor resistance

  • Open AccessOpen Access

    ARTICLE

    Betulinic acid-mediating miRNA-365 inhibited the progression of pancreatic cancer

    XIN LI1,2,#, WENKAI JIANG3,#, WANCHENG LI3,#, SHI DONG3, YAN DU3, HUI ZHANG1,*, WENCE ZHOU1,3,*
    Oncology Research, Vol.31, No.4, pp. 505-514, 2023, DOI:10.32604/or.2023.026959
    Abstract Background: The dilemma of pancreatic cancer treatment has become a global challenge. For this reason, effective, feasible, and new medical methods are currently much-needed. Betulinic acid (BA) has been valued as a potential therapy for pancreatic cancer. However, the mechanism by which BA exerts an inhibitory effect on the development of pancreatic cancer remains elusive. Methods: A rat model and two cell models of pancreatic cancer were established, and the effect of BA on pancreatic cancer was verified in vivo and in vitro by using MTT, Transwell, flow cytometry, RT-PCR, Elisa and immunohistochemistry. At the same time,… More >

    Graphic Abstract

    Betulinic acid-mediating miRNA-365 inhibited the progression of pancreatic cancer

  • Open AccessOpen Access

    ARTICLE

    The SMAD2/miR-4256/HDAC5/p16INK4a signaling axis contributes to gastric cancer progression

    MIN WANG1,#, HAILIANG ZHAO1,2,#, WEIWEI CHEN3,#, CAIQUN BIE4,#, JINYING YANG1, WENRUI CAI1, CHUTIAN WU1, YANFANG CHEN1, SHUFEN FENG1, YING SHI1, YUTING LI1, HUIJUN TANG4, LIXIAN ZHONG1, LILIANGZI GUO1, SISI CHEN1, LINJING LONG5, SHAOHUI TANG1,*
    Oncology Research, Vol.31, No.4, pp. 515-541, 2023, DOI:10.32604/or.2023.029101
    Abstract The dysregulation of exosomal microRNAs (miRNAs) plays a crucial role in the development and progression of cancer. This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer (GC) and the underlying mechanisms. The differentially expressed miRNAs were firstly identified in serum exosomes of GC patients and healthy individuals using next-generation sequencing and bioinformatics. Next, the expression of serum exosomal miR-4256 was analyzed in GC cells and GC tissues, and the role of miR-4256 in GC was investigated by in vitro and in vivo experiments. Then, the effect of miR-4256 on its… More >

    Graphic Abstract

    The SMAD2/miR-4256/HDAC5/p16<sup>INK4a</sup> signaling axis contributes to gastric cancer progression

  • Open AccessOpen Access

    ARTICLE

    Comprehensive analysis of the role of immune-related PANoptosis lncRNA model in renal clear cell carcinoma based on RNA transcriptome and single-cell sequencing

    WUYAO LIU, CHANGBAO QU, XIAOLU WANG*
    Oncology Research, Vol.31, No.4, pp. 543-567, 2023, DOI:10.32604/or.2023.029563
    (This article belongs to the Special Issue: Application of Multi-omics Analysis in Cancer Immunotherapy)
    Abstract The high immune infiltration and heterogeneity of the microenvironment in clear cell renal cell carcinoma (ccRCC) result in the variability of prognosis and clinical response. While PANoptosis has strong immunogenicity and is worthy of further study. In this study, data from The Cancer Genome Atlas database was used to obtain immune-related PANoptosis lncRNAs with prognostic value. Subsequently, the role of these lncRNAs in cancer immunity, progression and the therapeutic response was analyzed, and a new prediction model was constructed. Additionally, we further explored the biological value of PANoptosis-related lncRNAs using single-cell data from the Gene… More >

  • Open AccessOpen Access

    ARTICLE

    Construction of the panoptosis-related gene model and characterization of tumor microenvironment infiltration in hepatocellular carcinoma

    XINRUI SHI1, XIA GAO1, WENCONG LIU2, XUEJIAO TANG1, JIAYI LIU1, DONGCHEN PAN1, XUEQING DUAN1, YUQING JIN1, WEIYAN REN1, LEI YANG1,*, WENXUAN LIU1,*
    Oncology Research, Vol.31, No.4, pp. 569-590, 2023, DOI:10.32604/or.2023.028964
    (This article belongs to the Special Issue: Role of Reactive Oxygen Species and DNA Damage in Tumor Immunological Responses)
    Abstract Hepatocellular carcinoma (HCC) is the most common fatal cancer worldwide, patients with HCC have a high mortality rate and poor prognosis. PANoptosis is a novel discovery of programmed cell death associated with cancer development. However, the role of PANoptosis in HCC remains obscure. In this study, we enrolled 274 PANoptosisrelated genes (PANRGs) and screened 8 genes to set up a prognostic model. A previous scoring system calculated PANscore was utilized to quantify the individual risk level of each HCC patient, and the reliability of the prognostic model has been validated in an external cohort. Nomogram More >

  • Open AccessOpen Access

    ARTICLE

    System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer

    TIANMING SHI1,2,#, RONGRONG YAN1,2,#, MI HAN1,2,*
    Oncology Research, Vol.31, No.4, pp. 591-604, 2023, DOI:10.32604/or.2023.029282
    (This article belongs to the Special Issue: Transcriptome Analysis in Tumor Microenvironment and Tumor Heterogeneity)
    Abstract Ovarian cancer (OV) is highly heterogeneous tumor with a very poor prognosis. Studies increasingly show that T cell exhaustion is prognostically relevant in OV. The aim of this study was to dissect the heterogeneity of T cell subclusters in OV through single cell transcriptomic analysis. The single RNA-sequencing (scRNA-seq) data of five OV patients were analyzed, and six major cell clusters were identified after threshold screening. Further clustering of T cell-associated clusters revealed four subtypes. Pathways related to oxidative phosphorylation, G2M checkpoint, JAK-STAT and MAPK signaling were significantly activated, while the p53 pathway was inhibited… More >

    Graphic Abstract

    System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer

  • Open AccessOpen Access

    ARTICLE

    Mutations in epigenetic regulator KMT2C detected by liquid biopsy are associated with worse survival in prostate cancer patients

    SHA ZHU#, NANWEI XU#, JIAYU LIANG, FENGNIAN ZHAO, ZILIN WANG, YUCHAO NI, JINDONG DAI, JINGE ZHAO, XINGMING ZHANG, JUNRU CHEN, GUANGXI SUN, PENGFEI SHEN*, HAO ZENG*
    Oncology Research, Vol.31, No.4, pp. 605-614, 2023, DOI:10.32604/or.2023.028321
    Abstract Background: KMT2 (lysine methyltransferase) family enzymes are epigenetic regulators that activate gene transcription. KMT2C is mainly involved in enhancer-associated H3K4me1, and is also one of the top mutated genes in cancer (6.6% in pan-cancer). Currently, the clinical significance of KMT2C mutations in prostate cancer is understudied. Methods: We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study. We investigated the association between KMT2C mutations, other mutations, and pathways. Furthermore, we evaluated the prognostic value of KMT2C mutations, measured by… More >

  • Open AccessOpen Access

    ARTICLE

    YWHAH activates the HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect the proliferation of gastric cancer cells

    JUNYU HE1,2,3, FENG ZENG1,2,3, XI JIN1,2,3, LIN LIANG1,2,3, MENGXIANG GAO1,2,3, WENTAO LI1,2,3, GUIYUAN LI1,2,3, YANHONG ZHOU1,2,3,*
    Oncology Research, Vol.31, No.4, pp. 615-630, 2023, DOI:10.32604/or.2023.029698
    Abstract Fos-related antigen 1 (Fra-1) is a nuclear transcription factor that regulates cell growth, differentiation, and apoptosis. It is involved in the proliferation, invasion, apoptosis and epithelial mesenchymal transformation of malignant tumor cells. Fra-1 is highly expressed in gastric cancer (GC), affects the cycle distribution and apoptosis of GC cells, and participates in GC occurrence and development. However, the detailed mechanism of Fra-1 in GC is unclear, such as the identification of Fra-1-interacting proteins and their role in GC pathogenesis. In this study, we identified tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) as a Fra-1-interacting protein… More >

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