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New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle

Submission Deadline: 30 June 2025 View: 866 Submit to Special Issue

Guest Editors

Dr. Chen Li, Department of Biology, Chemistry, Pharmacy, Free University of Berlin, Germany. E-mail:chen.li.scholar@gmail.com; chen.li@fu-berlin.de

Dr. Ayman Moawad Mahmoud, Department of Life Sciences, Manchester Metropolitan University, Manchester, United Kingdom. E-mail:a.mahmoud@mmu.ac.uk

Summary

Although progress in anticancer therapy advancements was made somehow in the last decade, drug resistance of chemotherapy and immunotherapy with the subsequent spreading of metastases are the leading causes of failure in the treatment of multiple cancers. Drug resistance development involves dynamic changes of cancer heterogeneity as cancer evolves, as well as drug-induced physiological changes, specifically amplification/activation of oncogenes, loss/inactivation of tumor suppressor genes, dysregulation of transcriptional networks, altered metabolism, and microenvironment. Various clinical strategies, including combination therapies and epigenetic drugs, have been used to avoid or reverse drug resistance. Identifying both when the loss of efficacy in cancer drugs begins, and also the mechanism by which this resistance develops is of vital importance to clinicians and researchers tasked with identifying the issue, theorizing solutions, and implementing new treatments in the wake of resistance. The ultimate goal in these instances must be that of treating cancer and preventing further resistance development further down the line. By identifying these often unpredictable mechanisms of resistance, new refined drug molecules or drug delivery methods can be developed to avoid cancer drug resistance and ensure patient therapy is optimum. 

Keywords

Drug resistance; Cancer chemotherapy; cancer immunotherapy; Epigenetics

Published Papers

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  • Open Access

    ARTICLE

    Ultrasound genomics related mitochondrial gene signature for prognosis and neoadjuvant chemotherapy resistance in triple negative breast cancer

    HUAFANG HUANG, GUILIN WANG, DONGYUN ZENG, LUZ ANGELA TORRES-DE LA ROCHE, RUI ZHUO, RUDY LEON DE WILDE, WANWAN WANG, ULF D. KAHLERT, WENJIE SHI
    Oncology Research, DOI:10.32604/or.2024.054642
    （This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)
    Abstract Background: Neoadjuvant chemotherapy (NAC) significantly enhances clinical outcomes in patients with triple-negative breast cancer (TNBC); however, chemoresistance frequently results in treatment failure. Consequently, understanding the mechanisms underlying resistance and accurately predicting this phenomenon are crucial for improving treatment efficacy. Methods: Ultrasound images from 62 patients, taken before and after neoadjuvant therapy, were collected. Mitochondrial-related genes were extracted from a public database. Ultrasound features associated with NAC resistance were identified and correlated with significant mitochondrial-related genes. Subsequently, a prognostic model was developed and evaluated using the GSE58812 dataset. We also assessed this model alongside clinical factors… More >

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    29

  • Open Access

    REVIEW

    The regulatory role of lncRNA in tumor drug resistance: refracting light through a narrow aperture

    HENG ZHANG, XIAO YANG, YUJIN GUO, HAIBO ZHAO, PEI JIANG, QING-QING YU
    Oncology Research, DOI:10.32604/or.2024.053882
    （This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)
    Abstract As living conditions improve and diagnostic capabilities advance, the incidence of tumors has increased, with cancer becoming a leading cause of death worldwide. Surgery, chemotherapy, and radiotherapy are the most common treatments. Despite advances in treatment options, chemotherapy remains a routine first-line treatment for most tumors. Due to the continuous and extensive use of chemotherapy drugs, tumor resistance often develops, becoming a significant cause of treatment failure and poor prognosis. Recent research has increasingly focused on how long stranded non-coding RNAs (LncRNAs) influence the development of malignant tumors and drug resistance by regulating gene expression More >

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    26

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    1

  • Open Access

    ARTICLE

    Loss of TNFRSF21 induces cisplatin sensitivity in lung adenocarcinoma

    DAIEN ZHOU, HAOYANG YUAN, YIWEI HU, CHUXU WANG, SA GE, KOUFENG SHAO, HONGYING WANG, XIAOFENG TIAN, HAIBO HU
    Oncology Research, DOI:10.32604/or.2024.050182
    （This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)
    Abstract Background: Despite the identification of numerous therapeutic targets in lung cancer, achieving significant efficacy has been challenging. TNFRSF21 plays an important role in various cancers. We investigated the function of TNFRSF21 in lung adenocarcinoma (LUAD). Methods: The prognostic value of TNFRSF21 expression in lung cancer was evaluated by the GEPIA and Kaplan-Meier Plotter databases. Lung cancer cell viability was assessed by the CCK8 assay. TNFRSF21 expression patterns in lung cancer tissues and cells were examined using RT-PCR assay. Tumor sphere growth was evaluated through tumor sphere formation assays. MtROS contents in lung cancer cells were… More >

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    28

  • Open Access

    REVIEW

    Oncogenic and tumor-suppressive roles of Lipocalin 2 (LCN2) in tumor progression

    BAOXING HUANG, ZICHANG JIA, CHENCHEN FU, MOXIAN CHEN, ZEZHUO SU, YUNSHENG CHEN
    Oncology Research, DOI:10.32604/or.2024.051672
    （This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)
    Abstract Lipocalin-2 (LCN2) is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo. LCN2 is significantly expressed in various tumors and plays an important role in regulating tumor cell proliferation, invasion, and metastasis. The specific actions of LCN2 in tumors may vary depending on the particular type of cancer involved. In this review, we provide an extensive overview of the transcriptional and post-transcriptional regulation of LCN2 in health and disease. Furthermore, we summarize the impact of LCN2 dysregulation in a broad range More >

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  • Open Access

    ARTICLE

    Astragalus polysaccharide enhances the therapeutic efficacy of cisplatin in triple-negative breast cancer through multiple mechanisms

    LI SUN, SHICHAO ZHUO, XIAOXIN LI, HUSHENG KONG, WEIWEI DU, CHONG ZHOU, JUNXING HUANG
    Oncology Research, DOI:10.32604/or.2024.050057
    （This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)
    Abstract Background: Cisplatin (DDP) has been used in the treatment of various human cancers. However, DDP alone lacks efficacy in treating triple-negative breast cancer (TNBC), and its clinical application is often hampered by side effects. Astragalus polysaccharide (APS) is one of the active components extracted from Astragalus membranaceus and has gained attention for its various biological properties. This research is aimed to evaluate the effectiveness of a combination of APS and DDP on TNBC and explore the potential mechanisms. Methods: The efficacy and mechanisms of single or combined treatment were evaluated using Cell Counting Kit-8 (CCK8) assay, Annexin… More >

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    55

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    1

  • Open Access

    ARTICLE

    Genetic signatures of ERCC1 and ERCC2 expression, along with SNPs variants, unveil favorable prognosis in SCLC patients undergoing platinum-based chemotherapy

    ENRICO CALIMAN, SARA FANCELLI, FEDERICO SCOLARI, ADRIANO PASQUI, CLARA MANNESCHI, DANIELE LAVACCHI, FRANCESCA MAZZONI, FRANCESCA GENSINI, VALERIA PASINI, CAMILLA EVA COMIN, LUCA VOLTOLINI, SERENA PILLOZZI, LORENZO ANTONUZZO
    Oncology Research, DOI:10.32604/or.2024.050161
    （This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)
    Abstract Background: Platinum chemotherapy (CT) remains the backbone of systemic therapy for patients with small-cell lung cancer (SCLC). The nucleotide excision repair (NER) pathway plays a central role in the repair of the DNA damage exerted by platinum agents. Alteration in this repair mechanism may affect patients’ survival. Materials and Methods: We conducted a retrospective analysis of data from 38 patients with extensive disease (ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit, Careggi University Hospital, Florence (Italy), from 2015 to 2020. mRNA expression analysis and single nucleotide polymorphism (SNP) characterization of three NER pathway genes—namely ERCC1, ERCC2,… More >

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    59

  • Open Access

    ARTICLE

    The superiority of PMFs on reversing drug resistance of colon cancer and the effect on aerobic glycolysis-ROS-autophagy signaling axis

    YUQIN YIN, YU WU, HONGLIANG HUANG, YINGYING DUAN, ZHONGWEN YUAN, LIHUI CAO, JINJIN YING, YONGHENG ZHOU, SENLING FENG
    Oncology Research, Vol.32, No.12, pp. 1891-1902, 2024, DOI:10.32604/or.2024.048778
    （This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)
    Abstract Background: Polymethoxylated flavones (PMFs) are compounds present in citrus peels and other Rutaceae plants, which exhibit diverse biological activities, including robust antitumor and antioxidant effects. However, the mechanism of PMFs in reversing drug resistance to colon cancer remains unknown. In the present study, we aimed to investigate the potential connection between the aerobic glycolysis-ROS-autophagy signaling axis and the reversal of PTX resistance in colon cancer by PMFs. Methods: MTT Cell viability assay and colony formation assay were used to investigate the effect of PMFs combined with PTX in reversing HCT8/T cell resistance ex vivo; the mRNA… More >

    Graphic Abstract

    The superiority of PMFs on reversing drug resistance of colon cancer and the effect on aerobic glycolysis-ROS-autophagy signaling axis

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    166

  • Open Access

    ARTICLE

    Reversal of tamoxifen resistance by artemisinin in ER+ breast cancer: bioinformatics analysis and experimental validation

    ZHILI ZHUO, DONGNI ZHANG, WENPING LU, XIAOQING WU, YONGJIA CUI, WEIXUAN ZHANG, MENGFAN ZHANG
    Oncology Research, Vol.32, No.6, pp. 1093-1107, 2024, DOI:10.32604/or.2024.047257
    （This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)
    Abstract Breast cancer is the leading cause of cancer-related deaths in women worldwide, with Hormone Receptor (HR)+ being the predominant subtype. Tamoxifen (TAM) serves as the primary treatment for HR+ breast cancer. However, drug resistance often leads to recurrence, underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates. Artemisinin (ART) has demonstrated efficacy in inhibiting the growth of drug-resistant cells, positioning art as a viable option for counteracting endocrine resistance. This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental… More >

    Graphic Abstract

    Reversal of tamoxifen resistance by artemisinin in ER+ breast cancer: bioinformatics analysis and experimental validation

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    1041

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    252

  • Open Access

    ARTICLE

    A comparative in vitro study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

    SHAHID KARIM, ALANOUD NAHER ALGHANMI, MAHA JAMAL, HUDA ALKREATHY, ALAM JAMAL, HIND A. ALKHATABI, MOHAMMED BAZUHAIR, AFTAB AHMAD
    Oncology Research, Vol.32, No.5, pp. 817-830, 2024, DOI:10.32604/or.2024.048988
    （This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)
    Abstract Cancer frequently develops resistance to the majority of chemotherapy treatments. This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors, specifically Canagliflozin (CAN), Dapagliflozin (DAP), Empagliflozin (EMP), and Doxorubicin (DOX), using in vitro experimentation. The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin (DOX) in MCF-7 cells. Interestingly, it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth. Notably, when these medications were combined with DOX, there was a considerable inhibition of glucose consumption, as More >

    Graphic Abstract

    A comparative <i>in vitro</i> study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

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    1536

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    310

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