Special lssues

Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics

Submission Deadline: 30 December 2024 Submit to Special Issue

Guest Editors

Fu Wang, Xi’an Jiaotong University , China. E-mail: wangfu@xjtu.edu.cn

Lei Zhu, Emory University School of Medicine, USA. Email: lei.zhu@emory.edu

Jingang Huang, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China. Email: huangjg35@mail.sysu.edu.cn

Summary

Due to its high mortality and recurrence, malignant tumors remain the most concerned health problem of people all over the world. Liver, gastric, breast, colon and lung cancers are the top five malignant tumors in terms of mortality and morbidity. Molecular changes in cancer genes and related signaling pathways are used to provide new information for precise cancer treatment. Multiple signaling pathways, such as Janus kinase/signal transducers and activators of transcription (JAK-STAT), nuclear factor kappa B (NF-kB), mitogen-activated protein kinase (MAPK), cGAS/STING , and toll-like receptor (TLR) pathways, have been identified as pivotal regulators of the initiation and resolution of cancer progression. These pathways are widely concerned and crosstalked in the processes of solid tumors.   

 

Small molecule inhibitors and monoclonal antibodies against cancer related signaling pathways play an important role in the successful treatment of some malignancies. These drugs inhibit the signal pathways leading to cell growth arrest and apoptosis, and bind to external receptors that mediate antibody dependent cytotoxicity (ADCC). However, the inherent limitations, such as drug toxicity, and the acquisition of new or acquired drug resistance mechanisms, will still lead to treatment failure.

 

Therefore, in order to provide a new level of understanding of the molecular complexity underpinning resistance to cancer therapies, this special issue aims to explore the underlying mechanism of the molecules involved in the alterations of signaling pathways, further develop preferable combination therapies approach over monotherapy for cancer treatments. We welcome submissions of original research and review articles. We hope this special issue would provide novel therapeutic developments that may complement drug delivery and significantly benefit clinical response and outcomes of cancer patients.


Keywords

malignant tumors; signaling pathway; molecular targets; combinatorial treatments

Published Papers


  • Open Access

    ARTICLE

    Analysis of the role of dihydromyricetin derived from vine tea (Ampelopsis grossedentata) on multiple myeloma by activating STAT1/RIG-I axis

    WEI JIANG, MEI ZHOU
    Oncology Research, DOI:10.32604/or.2024.043423
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract Multiple myeloma (MM) is a plasma cell malignancy and remains incurable as it lacks effective curative approaches; thus, novel therapeutic strategies are desperately needed. The study aimed to explore the therapeutic role of dihydromyricetin (DHM) in MM and explore its mechanisms. Human MM and normal plasma samples, human MM cell lines, and normal plasma cells were used for in vitro experiments. Cell counting kit-8 (CCK-8), flow cytometry, and trans-well assays were performed for the assessment of cell viability, apoptosis, migration, and invasion, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA expression of signal transducer and… More >

    Graphic Abstract

    Analysis of the role of dihydromyricetin derived from vine tea (<i>Ampelopsis grossedentata</i>) on multiple myeloma by activating STAT1/RIG-I axis

  • Open Access

    ARTICLE

    lncRNA SNHG4 enhanced gastric cancer progression by modulating miR-409-3p/CREB1 axis

    ZHOUYANG CHENG, YUCHEN HUA, YANG CAO, JUN QIN
    Oncology Research, DOI:10.32604/or.2024.042281
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract Gastric cancer (GC) is a globally common cancer characterized by high incidence and mortality worldwide. Advances in the molecular understanding of GC provide promising targets for GC diagnosis and therapy. Long non-coding RNAs (lncRNAs) and their downstream regulators are regarded to be implicated in the progression of multiple types of malignancies. Studies have shown that the lncRNA small nucleolar RNA host gene 4 (SNHG4) serves as a tumor promoter in various malignancies, while its function in GC has yet to be characterized. Herein, we discovered that SNHG4 was overexpressed in GC tissues and cell lines, and was linked with poor… More >

  • Open Access

    ARTICLE

    Trametinib boosts palbociclib’s efficacy in breast cancer via autophagy inhibition

    ANGUO WU, JIAO YAN, TING SU, CHI FENG, XIN LONG, YIRU PAN, RUPEI YE, TIAN XIA, HANAN LONG, JIANMING WU, XIULI XIAO
    Oncology Research, DOI:10.32604/or.2024.046139
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract Breast cancer, a predominant global health issue, requires ongoing exploration of new therapeutic strategies. Palbociclib (PAL), a well-known cyclin-dependent kinase (CDK) inhibitor, plays a critical role in breast cancer treatment. While its efficacy is recognized, the interplay between PAL and cellular autophagy, particularly in the context of the RAF/MEK/ERK signaling pathway, remains insufficiently explored. This study investigates PAL’s inhibitory effects on breast cancer using both in vitro (MCF7 and MDA-MB-468 cells) and in vivo (tumor-bearing nude mice) models. Aimed at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib (TRA), an MEK… More >

    Graphic Abstract

    Trametinib boosts palbociclib’s efficacy in breast cancer via autophagy inhibition

  • Open Access

    ARTICLE

    Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling

    YUE ZHANG, WENYU YANG, XIAOWANG HAN, YUE QIAO, HAITAO WANG, TING CHEN, TIANYING LI, WEN-BIN OU
    Oncology Research, DOI:10.32604/or.2024.045025
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract It has been shown that the high expression of human epididymis protein 4 (HE4) in most lung cancers is related to the poor prognosis of patients, but the mechanism of pathological transformation of HE4 in lung cancer is still unclear. The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma (LUAD). Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies, and through analysis of The Cancer Genome Atlas (TCGA) dataset. Frequent HE4 overexpression was demonstrated in LUAD, but not in lung squamous cell carcinoma (LUSC), indicating that… More >

  • Open Access

    ARTICLE

    The Epstein-Barr virus-miRNA-BART6-5p regulates TGF-β/SMAD4 pathway to induce glycolysis and enhance proliferation and metastasis of gastric cancer cells

    XUHUI ZHAO, XIAOMIN HUANG, CHUNYAN DANG, XIA WANG, YUJIAO QI, HONGLING LI
    Oncology Research, Vol.32, No.5, pp. 999-1009, 2024, DOI:10.32604/or.2024.046679
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract Background: EBV-miR-BARTs exhibit significant relevance in epithelial tumors, particularly in EBV-associated gastric and nasopharyngeal cancers. However, their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored. Material and Methods: Initially, EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines. Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45, and downregulation in EBV-positive cells (SUN-719). The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation, migration, and glycolytic processes, with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-β inhibitor. Results: EBV-miRNA-BART6-5p exhibits pronounced upregulation… More >

  • Open Access

    ARTICLE

    Hydroxysafflor yellow A induced ferroptosis of Osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway

    YIWEN ZHU, LIU YANG, YING YU, YING XIONG, PING XIAO, XIAO FU, XIN LUO
    Oncology Research, Vol.32, No.5, pp. 899-910, 2024, DOI:10.32604/or.2023.042604
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal prognosis. Since there is no permanent therapy for this condition, it is necessary to develop a cure. Therefore, this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A (HYSA) in osteosarcoma cell lines (MG63). In this investigational study, MG63 cells were utilized. Microarray experiments, quantitative polymerase chain reaction (qPCR), immunofluorescent staining, extracellular acidification rate (ECAR), oxygen consumption rate (OCR), glucose consumption, lactate production, and ATP levels, proliferation assay, 5-Ethynyl-2′-deoxyuridine (EDU) staining, and Western blot were performed. In MG63… More >

  • Open Access

    ARTICLE

    Circ_0003855 involvement of esophageal cancer progression through miR-622/FLOT1

    JINGJING TIAN, XIBAO HU, XINRONG ZHANG
    Oncology Research, Vol.32, No.5, pp. 925-931, 2024, DOI:10.32604/or.2023.042447
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract To confirm the relationship between Circ_0003855 and EC, we purchased the Human esophageal carcinoma cell line Eca109 and normal human esophageal epithelial cells HEEC, and the expression levels of Circ_0003855, miR-622, and FLOT1 were detected. The results show that Circ_0003855 and FLOT1 were highly expressed in Eca109 cells, while miR-622 was lowly expressed (p < 0.05). Subsequently, Circ_0003855 small interfering RNA (si-Circ_0003855) and its negative control (si-NC) were used to detect changes in cellular biological behaviors. We found that the activity of Eca109 cells was reduced after interfering with the expression of Circ_0003855, and miR-622 expression was elevated, while FLOT1… More >

  • Open Access

    ARTICLE

    IQGAP3 promotes the progression of glioma as an immune and prognostic marker

    XIAOFENG GAO, JUANJUAN GE, XUZHENG GAO, NA MEI, YANTING SU, SHIGANG SHAN, WENBIN QIAN, JIANGHENG GUAN, ZHENWANG ZHANG, LONG WANG
    Oncology Research, Vol.32, No.4, pp. 659-678, 2024, DOI:10.32604/or.2023.046712
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract Background: IQGAP3 plays a crucial role in regulating cell proliferation, division, and cytoskeletal organization. Abnormal expression of IQGAP3 has been linked to various tumors, but its function in glioma is not well understood. Methods: Various methods, including genetic differential analysis, single-cell analysis, ROC curve analysis, Cox regression, Kaplan-Meier analysis, and enrichment analysis, were employed to analyze the expression patterns, diagnostic potential, prognostic implications, and biological processes involving IQGAP3 in normal and tumor tissues. The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence. Additionally, the cBioPortal database was used to analyze copy number… More >

    Graphic Abstract

    IQGAP3 promotes the progression of glioma as an immune and prognostic marker

  • Open Access

    ARTICLE

    Role of oncogenic long noncoding RNA KCNQ1OT1 in colon cancer

    GANG LIU, LEI SHI, BIN WANG, ZEHUI WU, HAIYUAN ZHAO, TIANYU ZHAO, LIANGHUI SHI
    Oncology Research, Vol.32, No.3, pp. 585-596, 2024, DOI:10.32604/or.2023.029349
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract The role of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in colon cancer involves various tumorigenic processes and has been studied widely. However, the mechanism by which it promotes colon cancer remains unclear. Retroviral vector pSEB61 was retrofitted in established HCT116-siKCN and SW480-siKCN cells to silence KCNQ1OT1. Cellular proliferation was measured using CCK8 assay, and flow cytometry (FCM) detected cell cycle changes. RNA sequencing (RNA-Seq) analysis showed differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to analyze enriched functions and signaling pathways. RT-qPCR, immunofluorescence, and western blotting… More >

  • Open Access

    ARTICLE

    Low-molecular-weight fucoidan inhibits the proliferation of melanoma via Bcl-2 phosphorylation and PTEN/AKT pathway

    MINJI PARK, CHULHWAN BANG, WON-SOO YUN, YUN-MI JEONG
    Oncology Research, Vol.32, No.2, pp. 273-282, 2024, DOI:10.32604/or.2023.044362
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract Fucoidan, a sulfate polysaccharide obtained from brown seaweed, has various bioactive properties, including anti-inflammatory, anti-cancer, anti-viral, anti-oxidant, anti-coagulant, anti-thrombotic, anti-angiogenic, and anti-Helicobacter pylori properties. However, the effects of low-molecular-weight fucoidan (LMW-F) on melanoma cell lines and three dimensional (3D) cell culture models are not well understood. This study aimed to investigate the effects of LMW-F on A375 human melanoma cells and cryopreserved biospecimens derived from patients with advanced melanoma. Ultrasonic wave was used to fragment fucoidan derived from Fucus vesiculosus into smaller LMW-F. MTT and live/dead assays showed that LMW-F inhibited cell proliferation in both A375 cells and patient-derived melanoma… More >

  • Open Access

    ARTICLE

    NAD+ associated genes as potential biomarkers for predicting the prognosis of gastric cancer

    XIANGDONG SUN, HUIJUAN WEN, FAZHAN LI, IHTISHAM BUKHARI, FEIFEI REN, XIA XUE, PENGYUAN ZHENG, YANG MI
    Oncology Research, Vol.32, No.2, pp. 283-296, 2024, DOI:10.32604/or.2023.044618
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract Nicotinamide adenine dinucleotide (NAD+) plays an essential role in cellular metabolism, mitochondrial homeostasis, inflammation, and senescence. However, the role of NAD+-regulated genes, including coding and long non-coding genes in cancer development is poorly understood. We constructed a prediction model based on the expression level of NAD+ metabolism-related genes (NMRGs). Furthermore, we validated the expression of NMRGs in gastric cancer (GC) tissues and cell lines; additionally, β-nicotinamide mononucleotide (NMN), a precursor of NAD+, was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation, cell cycle, apoptosis, and senescence-associated secretory… More >

    Graphic Abstract

    NAD+ associated genes as potential biomarkers for predicting the prognosis of gastric cancer

  • Open Access

    ARTICLE

    Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

    BEHROOZ JOHARI, MILAD PARVINZAD LEILAN, MAHMOUD GHARBAVI, YOUSEF MORTAZAVI, ALI SHARAFI, HAMED REZAEEJAM
    Oncology Research, Vol.32, No.2, pp. 309-323, 2024, DOI:10.32604/or.2023.043576
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract The Myc gene is the essential oncogene in triple-negative breast cancer (TNBC). This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line. Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene. The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan (Chi-Se-DEC), which was then encapsulated in niosome-nanocarriers (NISM@Chi-Se-DEC). FT-IR, DLS, FESEM, and hemolysis tests were applied to confirm its characterization and physicochemical properties. Moreover, cellular uptake, cellular toxicity, apoptosis, cell cycle, and scratch repair… More >

    Graphic Abstract

    Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

  • Open Access

    ARTICLE

    CHRM3 is a novel prognostic factor of poor prognosis and promotes glioblastoma progression via activation of oncogenic invasive growth factors

    BIN ZHANG, JIANYI ZHAO, YONGZHI WANG, HUA XU, BO GAO, GUANGNING ZHANG, BIN HAN, GUOHONG SONG, JUNCHEN ZHANG, WEI MENG
    Oncology Research, Vol.31, No.6, pp. 917-927, 2023, DOI:10.32604/or.2023.030425
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract Glioblastoma (GBM) is the most aggressive cancer of the brain and has a high mortality rate due to the lack of effective treatment strategy. Clarification of molecular mechanisms of GBM’s characteristic invasive growth are urgently needed to improve the poor prognosis. Single-nuclear sequencing of primary and recurrent GBM samples revealed that levels of M3 muscarinic acetylcholine receptor (CHRM3) were significantly higher in the recurrent samples than in the primary samples. Moreover, immunohistochemical staining of an array of GBM samples showed that high levels of CHRM3 correlated with poor prognosis, consistent with The Cancer Genome Atlas database. Knockdown of CHRM3 inhibited… More >

  • Open Access

    ARTICLE

    Transformer 2β regulates the alternative splicing of cell cycle regulatory genes to promote the malignant phenotype of ovarian cancer

    TING ZHOU, PEIYING FU, DONG CHEN, RONGHUA LIU
    Oncology Research, Vol.31, No.5, pp. 769-785, 2023, DOI:10.32604/or.2023.030166
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract Late-stage ovarian cancer (OC) has a poor prognosis and a high metastasis rate, but the underlying molecular mechanism is unclear. RNA binding proteins (RBPs) play important roles in posttranscriptional regulation in the contexts of neoplasia and tumor metastasis. In this study, we explored the molecular functions of a canonical RBP, Transformer 2β homolog (TRA2B), in cancer cells. TRA2B knockdown in HeLa cells and subsequent whole-transcriptome RNA sequencing (RNA-seq) analysis revealed the TRA2B-regulated alternative splicing (AS) profile. We disrupted TRA2B expression in epithelial OC cells and performed a series of experiments to confirm the resulting effects on OC cell proliferation, apoptosis… More >

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