Drug Resistance Updates最新文献

{"title":"Drug resistance mechanisms in dopamine agonist-resistant prolactin pituitary neuroendocrine tumors and exploration for new drugs","authors":"Jianhua Cheng ,&nbsp;Weiyan Xie ,&nbsp;Yiyuan Chen ,&nbsp;Yingxuan Sun ,&nbsp;Lei Gong ,&nbsp;Hongyun Wang ,&nbsp;Chuzhong Li ,&nbsp;Yazhuo Zhang","doi":"10.1016/j.drup.2024.101056","DOIUrl":"10.1016/j.drup.2024.101056","url":null,"abstract":"<div><h3>Background</h3><p>The treatment<span><span> of dopamine agonists<span> (DA) resistant prolactinomas remains a formidable challenge, as the mechanism of resistance is still unclear, and there are currently no viable alternative drug therapies available. This study seeks to investigate the mechanism of DA resistance in prolactinomas and identify new potentially effective </span></span>drugs.</span></p></div><div><h3>Methods</h3><p><span>To explore the mechanism of DA resistance in prolactinomas, this study conducted transcriptome sequencing analysis on 27 cases of DA-resistant prolactinomas and 10 cases of sensitive prolactinomas. In addition, single-cell sequencing analysis was performed on 3 cases of DA-resistant prolactinomas and 3 cases of sensitive prolactinomas. Furthermore, to screen for potential therapeutic drugs, the study successfully established an </span>organoids<span> model for DA-resistant prolactinomas and screened 180 small molecule compounds using 8 organoids. The efficacy of the identified drugs was verified through various assays, including CCK-8, colony formation, CTG, and flow cytometry, and their mechanisms of action were confirmed through WB and IHC. The effectiveness of the identified drugs was evaluated both in vitro and in vivo.</span></p></div><div><h3>Results</h3><p>The results of transcriptome sequencing and single-cell sequencing analyses showed that DA resistance in prolactinomas is associated with the upregulation of the Focal Adhesion<span><span><span> (FA) signaling pathway. Additionally, immunohistochemical validation revealed that FAK and </span>Paxillin were significantly upregulated in DA-resistant prolactinomas. Screening of 180 small molecule compounds using 8 organoids identified </span>Genistein<span><span> as a potentially effective drug for DA-resistant prolactinomas. Experimental validation demonstrated that Genistein inhibited the proliferation of pituitary tumor cell lines and organoids and promoted </span>apoptosis in pituitary tumor cells. Moreover, both the cell sequencing results and WB validation results of the drug-treated cells indicated that Genistein exerts its anti-tumor effect by inhibiting the FA pathway. In vivo, experiments also showed that Genistein can inhibit subcutaneous tumor formation.</span></span></p></div><div><h3>Conclusion</h3><p>DA resistance in prolactinomas is associated with upregulation of the Focal Adhesion (FA) signaling pathway, and Genistein can exert its anti-tumor effect by inhibiting the expression of the FA pathway.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139505822","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":"MAFF confers vulnerability to cisplatin-based and ionizing radiation treatments by modulating ferroptosis and cell cycle progression in lung adenocarcinoma","authors":"Jiaqi Liang ,&nbsp;Guoshu Bi ,&nbsp;Yiwei Huang ,&nbsp;Guangyin Zhao,&nbsp;Qihai Sui,&nbsp;Huan Zhang,&nbsp;Yunyi Bian,&nbsp;Jiacheng Yin,&nbsp;Qun Wang,&nbsp;Zhencong Chen,&nbsp;Cheng Zhan","doi":"10.1016/j.drup.2024.101057","DOIUrl":"10.1016/j.drup.2024.101057","url":null,"abstract":"<div><h3>Aims</h3><p>Lung cancer is the leading cause of cancer mortality and lung adenocarcinoma (LUAD) accounts for more than half of all lung cancer cases. Tumor elimination is mostly hindered by drug resistance and the mechanisms remain to be explored in LUAD.</p></div><div><h3>Methods</h3><p><span>CRISPR<span> screens in cell and murine models and single-cell RNA<span><span> sequencing were conducted, which identified MAF bZIP transcription factor F (MAFF) as a critical factor regulating tumor growth and treatment resistance in LUAD. RNA and </span>ChIP sequencing analyses were performed for transcriptional target expression and specific binding sites of MAFF. Functions of MAFF in inhibiting tumor growth and promoting </span></span></span>cisplatin<span> or irradiation efficacy were investigated using cellular and xenograft models.</span></p></div><div><h3>Results</h3><p><span><span>Patients with lung adenocarcinoma and reduced MAFF expression had worse clinical outcomes. MAFF inhibited tumor cell proliferation<span> by regulating the expression of SLC7A11, CDK6, and CDKN2C, promoting </span></span>ferroptosis<span> and preventing cell cycle progression from G1 to S. MAFF also conferred tumor cells vulnerable to cisplatin-based or </span></span>ionizing radiation treatments. MAFF reduction was a final event in the acquisition of cisplatin resistance of LUAD cells. The intracellular cAMP/PKA/CREB1 pathway upregulated MAFF in response to cisplatin-based or ionizing radiation treatments.</p></div><div><h3>Conclusions</h3><p>MAFF suppresses tumor growth, and pharmacological agonists targeting MAFF may improve cisplatin or irradiation therapies for lung adenocarcinoma patients.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139510563","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":"Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer","authors":"Fei Li ,&nbsp;Henghui Zhang ,&nbsp;Yuan Huang ,&nbsp;Dongqing Li ,&nbsp;Zaosong Zheng ,&nbsp;Kunfeng Xie ,&nbsp;Chun Cao ,&nbsp;Qiong Wang ,&nbsp;Xinlei Zhao ,&nbsp;Zehai Huang ,&nbsp;Shijun Chen ,&nbsp;Haiyong Chen ,&nbsp;Qin Fan ,&nbsp;Fan Deng ,&nbsp;Lina Hou ,&nbsp;Xiaolin Deng ,&nbsp;Wanlong Tan","doi":"10.1016/j.drup.2024.101059","DOIUrl":"10.1016/j.drup.2024.101059","url":null,"abstract":"<div><p><span>Patients with bladder cancer (BCa) frequently acquires resistance to platinum-based chemotherapy, particularly </span>cisplatin<span>. This study centered on the mechanism of cisplatin resistance in BCa and highlighted the pivotal role of lactylation in driving this phenomenon. Utilizing single-cell RNA sequencing<span>, we delineated the single-cell landscape of Bca, pinpointing a distinctive subset of BCa cells that exhibit marked resistance to cisplatin with association with glycolysis metabolism. Notably, we observed that H3 lysine 18 lactylation (H3K18la) plays a crucial role in activating the transcription of target genes by enriching in their promoter regions. Targeted inhibition of H3K18la effectively restored cisplatin sensitivity in these cisplatin-resistant epithelial cells. Furthermore, H3K18la-driven key transcription factors YBX1 and YY1 promote cisplatin resistance in BCa. These findings enhance our understanding of the mechanisms underlying cisplatin resistance, offering valuable insights for identifying novel intervention targets to overcome drug resistance in Bca.</span></span></p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139506064","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":"Tumor-associated macrophage (TAM)-secreted CCL22 confers cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells via regulating the activity of diacylglycerol kinase α (DGKα)/NOX4 axis","authors":"Jie Chen ,&nbsp;Di Zhao ,&nbsp;Lingyuan Zhang ,&nbsp;Jing Zhang ,&nbsp;Yuanfan Xiao ,&nbsp;Qingnan Wu ,&nbsp;Yan Wang ,&nbsp;Qimin Zhan","doi":"10.1016/j.drup.2024.101055","DOIUrl":"10.1016/j.drup.2024.101055","url":null,"abstract":"<div><p>Tumor-associated macrophages (TAMs) are often associated with chemoresistance and resultant poor clinical outcome in solid tumors. Here, we demonstrated that TAMs-released chemokine-C-C motif chemokine 22 (CCL22) in esophageal squamous cell carcinoma (ESCC) stroma was tightly correlated with the chemoresistance of ESCC patients. TAMs-secreted CCL22 was able to block the growth inhibitory and apoptosis-promoting effects of cisplatin on ESCC cells. Mechanistically, CCL22 stimulated intratumoral diacylglycerol kinase α (DGKα) to produce phosphatidic acid (PA), which suppressed the activity of NADPH oxidase 4 (NOX4) and then blocked the overproduction of intratumoral reactive species oxygen (ROS) induced by cisplatin. CCL22 activated DGKα/nuclear factor-κB (NF-κB) axis to upregulate the level of several members of ATP binding cassette (ABC) transporter superfamily, including ABC sub-family G member 4 (ABCG4), ABC sub-family A member 3 (ABCA3), and ABC sub-family A member 5 (ABCA5), to lower the intratumoral concentration of cisplatin. Consequently, these processes induced the cisplatin resistance in ESCC cells. In xenografted models, targeting DGKα with 5’-cholesterol-conjugated small-interfering (si) RNA enhanced the chemosensitivity of cisplatin in ESCC treatment, especially in the context of TAMs. Our data establish the correlation between the TAMs-induced intratumoral metabolic product/ROS axis and chemotherapy efficacy in ESCC treatment and reveal relevant molecular mechanisms.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139505787","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":"Inhibition of SIRT7 overcomes sorafenib acquired resistance by suppressing ERK1/2 phosphorylation via the DDX3X-mediated NLRP3 inflammasome in hepatocellular carcinoma","authors":"Yuna Kim ,&nbsp;Kwan-Young Jung ,&nbsp;Yun Hak Kim ,&nbsp;Pan Xu ,&nbsp;Baeki E. Kang ,&nbsp;Yunju Jo ,&nbsp;Navin Pandit ,&nbsp;Jeongho Kwon ,&nbsp;Karim Gariani ,&nbsp;Joanna Gariani ,&nbsp;Junguee Lee ,&nbsp;Jef Verbeek ,&nbsp;Seungyoon Nam ,&nbsp;Sung-Jin Bae ,&nbsp;Ki-Tae Ha ,&nbsp;Hyon-Seung Yi ,&nbsp;Minho Shong ,&nbsp;Kyun-Hwan Kim ,&nbsp;Doyoun Kim ,&nbsp;Hee Jung Jung ,&nbsp;Dongryeol Ryu","doi":"10.1016/j.drup.2024.101054","DOIUrl":"10.1016/j.drup.2024.101054","url":null,"abstract":"<div><h3>Aims</h3><p>Sirtuin 7 (SIRT7) plays an important role in tumor development, and has been characterized as a potent regulator of cellular stress. However, the effect of SIRT7 on sorafenib acquired resistance remains unclear and a possible anti-tumor mechanism beyond this process in HCC has not been clarified. We examined the therapeutic potential of SIRT7 and determined whether it functions synergistically with sorafenib to overcome chemoresistance.</p></div><div><h3>Methods</h3><p>Cancer Genome Atlas-liver HCC data and unbiased gene set enrichment analyses were used to identify SIRT7 as a potential effector molecule in sorafenib acquired resistance. Two types of SIRT7 chemical inhibitors were developed to evaluate its therapeutic properties when synergized with sorafenib. Mass spectrometry was performed to discover a direct target of SIRT7, DDX3X, and DDX3X deacetylation levels and protein stability were explored. Moreover, an in vivo xenograft model was used to confirm anti-tumor effect of SIRT7 and DDX3X chemical inhibitors combined with sorafenib.</p></div><div><h3>Results</h3><p>SIRT7 inhibition mediated DDX3X depletion can re-sensitize acquired sorafenib resistance by disrupting NLRP3 inflammasome assembly, finally suppressing hyperactive ERK1/2 signaling in response to NLRP3 inflammasome-mediated IL-1β inhibition.</p></div><div><h3>Conclusions</h3><p>SIRT7 is responsible for sorafenib acquired resistance, and its inhibition would be beneficial when combined with sorafenib by suppressing hyperactive pro-cell survival ERK1/2 signaling.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764624000128/pdfft?md5=02ff5356ad100a6049db90104b8ff83d&pid=1-s2.0-S1368764624000128-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139489743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual specific phosphatase 4 suppresses ferroptosis and enhances sorafenib resistance in hepatocellular carcinoma","authors":"Shi-Hui Hao ,&nbsp;Xiao-Dan Ma ,&nbsp;Li Xu ,&nbsp;Jing-Dun Xie ,&nbsp;Zi-Hao Feng ,&nbsp;Jie-Wei Chen ,&nbsp;Ri-Xin Chen ,&nbsp;Feng-Wei Wang ,&nbsp;Yu-Hao Tang ,&nbsp;Dan Xie ,&nbsp;Mu-Yan Cai","doi":"10.1016/j.drup.2024.101052","DOIUrl":"10.1016/j.drup.2024.101052","url":null,"abstract":"<div><h3>Aims</h3><p>This investigation aims to elucidate the mechanism underlying sorafenib-induced ferroptosis<span> in hepatocellular carcinoma (HCC).</span></p></div><div><h3>Methods</h3><p><span><span><span><span>The role of dual specificity phosphatase 4 (DUSP4) in sorafenib-treated HCC was investigated using comprehensive assessments both in vitro and in vivo, including </span>Western blotting, qRT-PCR, </span>cell viability<span> assay, lipid </span></span>reactive oxygen species (ROS) assay, </span>immunohistochemistry<span>, and xenograft<span> tumor mouse model. Additionally, label-free quantitative proteomics was employed to identify potential proteins associated with DUSP4.</span></span></p></div><div><h3>Results</h3><p><span>Our study revealed that suppression of DUSP4 expression heightens the susceptibility of HCC cells to ferroptosis inducers, specifically sorafenib and erastin, in both </span><em>in vitro</em> and <em>in vivo</em><span><span><span> settings. Furthermore, we identified DUSP4-mediated regulation of key ferroptosis-related markers, such as ferritin light chain (FTL) and ferritin heavy chain 1 (FTH1). Notably, label-free quantitative proteomics unveiled the phosphorylation of </span>threonine residue T148 on YTH Domain Containing 1 (YTHDC1) by DUSP4. Further investigations unraveled that YTHDC1, functioning as an mRNA nuclear export regulator, is a direct target of DUSP4, orchestrating the </span>subcellular localization of FTL and FTH1 mRNAs. Significantly, our study highlights a strong correlation between elevated DUSP4 expression and sorafenib resistance in HCC.</span></p></div><div><h3>Conclusions</h3><p>Our findings introduce DUSP4 as a negative regulator of sorafenib-induced ferroptosis. This discovery opens new avenues for the development of ferroptosis-based therapeutic strategies tailored for HCC treatment.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139407383","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":"Tyrosine phosphorylation-mediated YAP1-TFAP2A interactions coordinate transcription and trastuzumab resistance in HER2+ breast cancer","authors":"Hailin Zou ,&nbsp;Juan Luo ,&nbsp;Yibo Guo ,&nbsp;Liang Deng ,&nbsp;Leli Zeng ,&nbsp;Yihang Pan ,&nbsp;Peng Li","doi":"10.1016/j.drup.2024.101051","DOIUrl":"10.1016/j.drup.2024.101051","url":null,"abstract":"<div><p>Trastuzumab resistance in HER2+ breast cancer (BC) is the major reason leading to poor prognosis of BC patients. Oncogenic gene overexpression or aberrant activation of tyrosine kinase SRC is identified to be the key modulator of trastuzumab response. However, the detailed regulatory mechanisms underlying SRC activation-associated trastuzumab resistance remain poorly understood. In the present study, we discover that SRC-mediated YAP1 tyrosine phosphorylation facilitates its interaction with transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha, TFAP2A), which in turn promotes YAP1/TEAD-TFAP2A (YTT) complex-associated transcriptional outputs, thereby conferring trastuzumab resistance in HER2+ BC. Inhibition of SRC kinase activity or disruption of YTT complex sensitizes cells to trastuzumab treatment in vitro and in vivo. Additionally, we also identify YTT complex co-occupies the regulatory regions of a series of genes related to trastuzumab resistance and directly regulates their transcriptions, including <em>EGFR</em>, <em>HER2</em>, <em>H19</em> and <em>CTGF</em>. Moreover, YTT-mediated transcriptional regulation is coordinated by SRC kinase activity. Taken together, our study reveals that SRC-mediated YTT complex formation and transcriptions are responsible for multiple mechanisms associated with trastuzumab resistance. Therefore, targeting HER2 signaling in combination with the inhibition of YTT-associated transcriptional outputs could serve as the treatment strategy to overcome trastuzumab resistance caused by SRC activation.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764624000098/pdfft?md5=f58b6eca10637d91d4984908e3f72c5c&pid=1-s2.0-S1368764624000098-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139407215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NDRG1 overcomes resistance to immunotherapy of pancreatic ductal adenocarcinoma through inhibiting ATG9A-dependent degradation of MHC-1","authors":"Zhiheng Zhang ,&nbsp;Bojiao Song ,&nbsp;Haowei Wei ,&nbsp;Yang Liu ,&nbsp;Wenjie Zhang ,&nbsp;Yuhong Yang ,&nbsp;Beicheng Sun","doi":"10.1016/j.drup.2023.101040","DOIUrl":"10.1016/j.drup.2023.101040","url":null,"abstract":"<div><h3>Aims</h3><p><span>Pancreatic ductal adenocarcinoma<span> (PDAC) is a deadly disease that is resistant to immune checkpoint blockade (ICB) therapies. Emerging evidence suggests that NDRG1 may be an important target for the development of new therapies for PDAC. Herein, we investigated the novel roles of NDRG1 and Combretastatin A-4 (CA-4) in the </span></span>treatment of PDAC ICB resistance.</p></div><div><h3>Methods</h3><p><span><span><span>Enrichment of MHC class I<span> was detected by RNA sequence and verified by RT-qPCR and </span></span>immunoblotting in NDRG1-knockdown human </span>pancreatic cancer<span> cell lines. The protein degradation<span> mode was found by stimulation with various inhibitors, and the autophagy degradation pathway was found by immunoprecipitation and </span></span></span>immunolocalization<span><span>. The roles of NDRG1 and MHC-I in immunotherapy<span> were investigated by orthotopic solid tumors, histology, </span></span>immunohistochemistry<span>, multiplex immunofluorescence staining and flow cytometry.</span></span></p></div><div><h3>Results</h3><p><span>Here, we identified a previously undescribed role of NDRG1 in activating major histocompatibility complex class 1 (MHC-1) expression in pancreatic ductal adenocarcinoma (PDAC) cells through lysosomal-autophagy-dependent degradation. In mouse models of PDAC, either tumor cell overexpression or pharmacologic activation of NDRG1 leads to MHC-1 upregulation in tumor cells, which in turn promotes the infiltration and activity of </span>CD8<span> + T cells, enhances anti-tumor immunity, and overcomes resistance to ICB therapy. Moreover, combination therapy of CA-4 and ICB overcomes the drug resistance of pancreatic cancer to ICB therapy. In PDAC patients, NDRG1 expression correlates with high MHC-1 expression and better survival.</span></p></div><div><h3>Conclusion</h3><p><span>Our results reveal NDRG1 in PDAC cancer cells as a </span>tumor suppressor and suggest that pharmaceutically targeting NDRG1 is a promising way to overcome pancreatic cancer resistance to immunotherapy and provides a potential therapeutic strategy for the treatment of pancreatic cancer patients.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139407236","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":"Inhibition of NF-κB signaling unveils novel strategies to overcome drug resistance in cancers","authors":"Yuanfang Li ,&nbsp;Baiwei Zhao ,&nbsp;Juzheng Peng ,&nbsp;Hailin Tang ,&nbsp;Sicheng Wang ,&nbsp;Sicheng Peng ,&nbsp;Feng Ye ,&nbsp;Junye Wang ,&nbsp;Kai Ouyang ,&nbsp;Jianjun Li ,&nbsp;Manbo Cai ,&nbsp;Yongming Chen","doi":"10.1016/j.drup.2023.101042","DOIUrl":"10.1016/j.drup.2023.101042","url":null,"abstract":"<div><p>Drug resistance in cancer remains a major challenge in oncology, impeding the effectiveness of various treatment modalities. The nuclear factor-kappa B (NF-κB) signaling pathway has emerged as a critical player in the development of drug resistance in cancer cells. This comprehensive review explores the intricate relationship between NF-κB and drug resistance in cancer. We delve into the molecular mechanisms through which NF-κB activation contributes to resistance against chemotherapeutic agents, targeted therapies, and immunotherapies. Additionally, we discuss potential strategies to overcome this resistance by targeting NF-κB signaling, such as small molecule inhibitors and combination therapies. Understanding the multifaceted interactions between NF-κB and drug resistance is crucial for the development of more effective cancer treatment strategies. By dissecting the complex signaling network of NF-κB, we hope to shed light on novel therapeutic approaches that can enhance treatment outcomes, ultimately improving the prognosis for cancer patients. This review aims to provide a comprehensive overview of the current state of knowledge on NF-κB and its role in drug resistance, offering insights that may guide future research and therapeutic interventions in the fight against cancer.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764623001255/pdfft?md5=01eeba418c6b41febe4bea5ea3d5ecd8&pid=1-s2.0-S1368764623001255-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139091541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The promising role of tumor-associated macrophages in the treatment of cancer","authors":"Hongbin Wang ,&nbsp;Xueying Wang ,&nbsp;Xin Zhang ,&nbsp;Wanhai Xu","doi":"10.1016/j.drup.2023.101041","DOIUrl":"10.1016/j.drup.2023.101041","url":null,"abstract":"<div><p><span><span><span>Macrophages are important components of the immune system<span><span>. Mature macrophages can be recruited to tumor microenvironment that affect tumor </span>cell proliferation, invasion and </span></span>metastasis, </span>extracellular matrix<span> remodeling, immune suppression, as well as chemotherapy resistance. Classically activated type I macrophages (M1) exhibited marked tumor killing and </span></span>phagocytosis<span>. Therefore, using macrophages for adoptive cell therapy has attracted attention and become one of the most effective strategies for cancer treatment. Through cytokines and/or chemokines<span>, macrophage can inhibit myeloid cells recruitment, and activate anti-tumor and immune killing functions. Applying macrophages for anti-tumor delivery is one of the most promising approaches for cancer therapy. This review article introduces the role of macrophages in tumor development and drug resistance, and the possible clinical application of targeting macrophages for overcoming drug resistance and enhancing cancer therapeutics, as well as its challenges.</span></span></p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":null,"pages":null},"PeriodicalIF":24.3,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139091659","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}