Pub Date : 2024-09-10eCollection Date: 2024-01-01DOI: 10.20517/cdr.2024.55
Samaneh Tokhanbigli, Mehra Haghi, Kamal Dua, Brian Gregory George Oliver
Cancer-associated fibroblasts (CAFs) are the vital constituent of the tumor microenvironment, and in communication with other cells, they contribute to tumor progression and metastasis. Fibroblasts are the proposed origin of CAFs, which are mediated by pro-inflammatory cytokines and the recruitment of immune cells akin to wound healing. Although various studies have identified different subpopulations of CAFs in lung cancer, the heterogeneity of CAFs, particularly in lung cancer, and their potential as a therapeutic target remain largely unknown. Notwithstanding CAFs were previously thought to have predominantly tumor-promoting features, their pro- or anti-tumorigenic properties may depend on various conditions and cell origins. The absence of distinct markers to identify CAF subpopulations presents obstacles to the successful therapeutic targeting and treatment of CAFs in cancer. Human clinical and animal studies targeting CAFs have shown that targeting CAFs exacerbates the disease progression, suggesting that subpopulations of CAFs may exert opposing functions in cancer progression. Therefore, it is essential to pinpoint specific markers capable of characterizing these subpopulations and revealing their mechanisms of function. The cell-specific surface markers of CAFs will serve as an initial step in investigating precise CAF subpopulations and their role in diagnosing and targeting therapy against cancer-promoting CAF subsets in lung cancer.
{"title":"Cancer-associated fibroblast cell surface markers as potential biomarkers or therapeutic targets in lung cancer.","authors":"Samaneh Tokhanbigli, Mehra Haghi, Kamal Dua, Brian Gregory George Oliver","doi":"10.20517/cdr.2024.55","DOIUrl":"https://doi.org/10.20517/cdr.2024.55","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) are the vital constituent of the tumor microenvironment, and in communication with other cells, they contribute to tumor progression and metastasis. Fibroblasts are the proposed origin of CAFs, which are mediated by pro-inflammatory cytokines and the recruitment of immune cells akin to wound healing. Although various studies have identified different subpopulations of CAFs in lung cancer, the heterogeneity of CAFs, particularly in lung cancer, and their potential as a therapeutic target remain largely unknown. Notwithstanding CAFs were previously thought to have predominantly tumor-promoting features, their pro- or anti-tumorigenic properties may depend on various conditions and cell origins. The absence of distinct markers to identify CAF subpopulations presents obstacles to the successful therapeutic targeting and treatment of CAFs in cancer. Human clinical and animal studies targeting CAFs have shown that targeting CAFs exacerbates the disease progression, suggesting that subpopulations of CAFs may exert opposing functions in cancer progression. Therefore, it is essential to pinpoint specific markers capable of characterizing these subpopulations and revealing their mechanisms of function. The cell-specific surface markers of CAFs will serve as an initial step in investigating precise CAF subpopulations and their role in diagnosing and targeting therapy against cancer-promoting CAF subsets in lung cancer.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"7 ","pages":"32"},"PeriodicalIF":4.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02eCollection Date: 2024-01-01DOI: 10.20517/cdr.2024.57
Hongli Zeng, Junshang Ge, Yi Meng, Qian Wang, Mei Yang, Zhaoyang Zeng, Wei Xiong, Xuyu Zu
Drug resistance in tumors constitutes a significant obstacle to tumor therapy. Head and neck squamous cell carcinoma (HNSCC) presents a major challenge due to its deep anatomical location, limited space, and complex structure. These factors complicate surgical procedures and hinder the effectiveness of chemoradiotherapy, leading to poor prognosis and reduced quality of life. However, there is hope in the form of circular RNAs (circRNAs), non-coding RNA molecules with a closed-loop structure that exhibits superior stability and resistance to degradation compared to linear RNAs. Recent advances in high-throughput sequencing and bioinformatics technology revealed that circRNAs participate in tumor proliferation, invasion, migration, and drug resistance. This review aims to summarize current research progress on the involvement of circRNAs in drug resistance of HNSCC and provide valuable insights for the prevention and mitigation of drug resistance in HNSCC.
{"title":"Research progress on the role and mechanism of circular RNA in drug resistance of head and neck squamous cell carcinoma.","authors":"Hongli Zeng, Junshang Ge, Yi Meng, Qian Wang, Mei Yang, Zhaoyang Zeng, Wei Xiong, Xuyu Zu","doi":"10.20517/cdr.2024.57","DOIUrl":"https://doi.org/10.20517/cdr.2024.57","url":null,"abstract":"<p><p>Drug resistance in tumors constitutes a significant obstacle to tumor therapy. Head and neck squamous cell carcinoma (HNSCC) presents a major challenge due to its deep anatomical location, limited space, and complex structure. These factors complicate surgical procedures and hinder the effectiveness of chemoradiotherapy, leading to poor prognosis and reduced quality of life. However, there is hope in the form of circular RNAs (circRNAs), non-coding RNA molecules with a closed-loop structure that exhibits superior stability and resistance to degradation compared to linear RNAs. Recent advances in high-throughput sequencing and bioinformatics technology revealed that circRNAs participate in tumor proliferation, invasion, migration, and drug resistance. This review aims to summarize current research progress on the involvement of circRNAs in drug resistance of HNSCC and provide valuable insights for the prevention and mitigation of drug resistance in HNSCC.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"7 ","pages":"31"},"PeriodicalIF":4.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicroRNAs (miRNAs) are small non-coding RNAs comprising 19-24 nucleotides that indirectly control gene expression. In contrast to other non-coding RNAs (ncRNAs), circular RNAs (circRNAs) are defined by their covalently closed loops, forming covalent bonds between the 3' and 5' ends. circRNAs regulate gene expression by interacting with miRNAs at transcriptional or post-transcriptional levels. Accordingly, circRNAs and miRNAs control many biological events related to cancer, including cell proliferation, metabolism, cell cycle, and apoptosis. Both circRNAs and miRNAs are involved in the pathogenesis of diseases, such as breast cancer. This review focuses on the latest discoveries on dysregulated circRNAs and miRNAs related to breast cancer, highlighting their potential as biomarkers for clinical diagnosis, prognosis, and chemotherapy response.
{"title":"The role of circRNAs and miRNAs in drug resistance and targeted therapy responses in breast cancer.","authors":"Meilan Zhang, Zhaokuan Zheng, Shouliang Wang, Ruihan Liu, Mengli Zhang, Zhiyun Guo, Hao Wang, Weige Tan","doi":"10.20517/cdr.2024.62","DOIUrl":"https://doi.org/10.20517/cdr.2024.62","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are small non-coding RNAs comprising 19-24 nucleotides that indirectly control gene expression. In contrast to other non-coding RNAs (ncRNAs), circular RNAs (circRNAs) are defined by their covalently closed loops, forming covalent bonds between the 3' and 5' ends. circRNAs regulate gene expression by interacting with miRNAs at transcriptional or post-transcriptional levels. Accordingly, circRNAs and miRNAs control many biological events related to cancer, including cell proliferation, metabolism, cell cycle, and apoptosis. Both circRNAs and miRNAs are involved in the pathogenesis of diseases, such as breast cancer. This review focuses on the latest discoveries on dysregulated circRNAs and miRNAs related to breast cancer, highlighting their potential as biomarkers for clinical diagnosis, prognosis, and chemotherapy response.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"7 ","pages":"30"},"PeriodicalIF":4.6,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07eCollection Date: 2024-01-01DOI: 10.20517/cdr.2024.56
Louise Gerard, Jean-Pierre Gillet
The ABCB5 gene encodes several isoforms, including two transporters (i.e., ABCB5FL, ABCB5β) and several soluble proteins, such as ABCB5α which has been hypothesized to have a regulatory function. ABCB5FL is a full ABC transporter and is expressed in the testis and prostate, whereas ABCB5β is an atypical half-transporter with a ubiquitous expression pattern. ABCB5β has been shown to mark cancer stem cells in several cancer types. In addition, ABCB5β and ABCB5FL have been shown to play a role in tumorigenesis and multidrug resistance. However, ABCB5β shares its entire protein sequence with ABCB5FL, making them difficult to distinguish. It cannot be excluded that some biological effects described for one transporter may be mediated by the other isoform. Therefore, it is difficult to interpret the available data and some controversies remain regarding their function in cancer cells. In this review, we discuss the data collected on ABCB5 isoforms over the last 20 years and propose a common ground on which we can build further to unravel the pathophysiological roles of ABCB5 transporters.
{"title":"The uniqueness of ABCB5 as a full transporter ABCB5FL and a half-transporter-like ABCB5β.","authors":"Louise Gerard, Jean-Pierre Gillet","doi":"10.20517/cdr.2024.56","DOIUrl":"https://doi.org/10.20517/cdr.2024.56","url":null,"abstract":"<p><p>The <i>ABCB5</i> gene encodes several isoforms, including two transporters (i.e., ABCB5FL, ABCB5β) and several soluble proteins, such as ABCB5α which has been hypothesized to have a regulatory function. ABCB5FL is a full ABC transporter and is expressed in the testis and prostate, whereas ABCB5β is an atypical half-transporter with a ubiquitous expression pattern. ABCB5β has been shown to mark cancer stem cells in several cancer types. In addition, ABCB5β and ABCB5FL have been shown to play a role in tumorigenesis and multidrug resistance. However, ABCB5β shares its entire protein sequence with ABCB5FL, making them difficult to distinguish. It cannot be excluded that some biological effects described for one transporter may be mediated by the other isoform. Therefore, it is difficult to interpret the available data and some controversies remain regarding their function in cancer cells. In this review, we discuss the data collected on ABCB5 isoforms over the last 20 years and propose a common ground on which we can build further to unravel the pathophysiological roles of ABCB5 transporters.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"7 ","pages":"29"},"PeriodicalIF":4.6,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-26eCollection Date: 2024-01-01DOI: 10.20517/cdr.2024.39
Jacqueline Schütt, Kerstin Brinkert, Andrzej Plis, Tino Schenk, Annamaria Brioli
Despite significant advances in the understanding of multiple myeloma (MM) biology and the development of novel treatment strategies in the last two decades, MM is still an incurable disease. Novel drugs with alternative mechanisms of action, such as selective inhibitors of nuclear export (SINE), modulators of the ubiquitin pathway [cereblon E3 ligase modulatory drugs (CELMoDs)], and T cell redirecting (TCR) therapy, have led to significant improvement in patient outcomes. However, resistance still emerges, posing a major problem for the treatment of myeloma patients. This review summarizes current data on treatment with SINE, TCR therapy, and CELMoDs and explores their mechanism of resistance. Understanding these resistance mechanisms is critical for developing strategies to overcome treatment failure and improve therapeutic outcomes.
{"title":"Unraveling the complexity of drug resistance mechanisms to SINE, T cell-engaging therapies and CELMoDs in multiple myeloma: a comprehensive review.","authors":"Jacqueline Schütt, Kerstin Brinkert, Andrzej Plis, Tino Schenk, Annamaria Brioli","doi":"10.20517/cdr.2024.39","DOIUrl":"https://doi.org/10.20517/cdr.2024.39","url":null,"abstract":"<p><p>Despite significant advances in the understanding of multiple myeloma (MM) biology and the development of novel treatment strategies in the last two decades, MM is still an incurable disease. Novel drugs with alternative mechanisms of action, such as selective inhibitors of nuclear export (SINE), modulators of the ubiquitin pathway [cereblon E3 ligase modulatory drugs (CELMoDs)], and T cell redirecting (TCR) therapy, have led to significant improvement in patient outcomes. However, resistance still emerges, posing a major problem for the treatment of myeloma patients. This review summarizes current data on treatment with SINE, TCR therapy, and CELMoDs and explores their mechanism of resistance. Understanding these resistance mechanisms is critical for developing strategies to overcome treatment failure and improve therapeutic outcomes.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"7 ","pages":"26"},"PeriodicalIF":4.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: This study aimed to investigate drug candidates and their efficacy in treating refractory multiple myeloma (MM) despite significant therapeutic advances and the introduction of novel agents. Our study focused on how myeloma cells mediate the metabolic pathways essential for survival. Therefore, we examined the role of glutaminolysis in this process. Methods: We investigated the role of glutaminolysis in myeloma cell growth. In addition, we analyzed the ability of CB-839 (telaglenastat), a glutaminase (GLS) inhibitor, to suppress myeloma cell proliferation and enhance the sensitivity to histone deacetylase (HDAC) inhibitors. Results: Glutamate deprivation significantly reduced MM cell proliferation. We observed an upregulation of GLS1 expression in MM cell lines compared to that in normal controls. CB-839 inhibits MM cell proliferation in a dose-dependent manner, resulting in enhanced cytotoxicity. Additionally, intracellular α-ketoglutarate and nicotinamide adenine dinucleotide phosphate levels decreased after CB-839 administration. Combining panobinostat with CB-839 resulted in enhanced cytotoxicity and increased caspase 3/7 activity. Cells transfected with GLS shRNA exhibited reduced cell viability and elevated sub-G1 phase according to cell cycle analysis results. Compared to control cells, these cells also showed increased sensitivity to panobinostat. Conclusion: Glutaminolysis contributes to the viability of MM cells, and the GLS inhibitor CB-839 has been proven to be an effective treatment for enhancing the cytotoxic effect of HDAC inhibition. These results are clinically relevant and suggest that CB-839 is a potential therapeutic candidate for patients with MM.
目的:本研究旨在调查候选药物及其在治疗难治性多发性骨髓瘤(MM)方面的疗效,尽管在治疗方面取得了重大进展并引入了新型药物。我们的研究重点是骨髓瘤细胞如何介导生存所必需的代谢途径。因此,我们研究了谷氨酰胺溶解在这一过程中的作用。研究方法我们研究了谷氨酰胺分解在骨髓瘤细胞生长中的作用。此外,我们还分析了谷氨酰胺酶(GLS)抑制剂 CB-839(替拉格纳司他)抑制骨髓瘤细胞增殖并提高其对组蛋白去乙酰化酶(HDAC)抑制剂敏感性的能力。研究结果谷氨酸剥夺能明显减少骨髓瘤细胞的增殖。与正常对照组相比,我们在 MM 细胞系中观察到 GLS1 表达上调。CB-839 以剂量依赖的方式抑制 MM 细胞增殖,从而增强细胞毒性。此外,服用 CB-839 后,细胞内的α-酮戊二酸和烟酰胺腺嘌呤二核苷酸磷酸酯水平下降。将帕诺比诺司他(panobinostat)与 CB-839 结合使用可增强细胞毒性并提高 caspase 3/7 活性。细胞周期分析结果显示,转染 GLS shRNA 的细胞存活率降低,亚 G1 期升高。与对照细胞相比,这些细胞对泛比诺司他的敏感性也有所提高。结论谷氨酰胺溶解有助于提高 MM 细胞的活力,而 GLS 抑制剂 CB-839 已被证明是增强 HDAC 抑制的细胞毒性效果的有效治疗方法。这些结果与临床相关,表明 CB-839 是 MM 患者的潜在候选治疗药物。
{"title":"Inhibition of glutaminolysis alone and in combination with HDAC inhibitor has anti-myeloma therapeutic effects.","authors":"Seiichi Okabe, Yuko Tanaka, Mitsuru Moriyama, Akihiko Gotoh","doi":"10.20517/cdr.2024.35","DOIUrl":"https://doi.org/10.20517/cdr.2024.35","url":null,"abstract":"<p><p><b>Aim:</b> This study aimed to investigate drug candidates and their efficacy in treating refractory multiple myeloma (MM) despite significant therapeutic advances and the introduction of novel agents. Our study focused on how myeloma cells mediate the metabolic pathways essential for survival. Therefore, we examined the role of glutaminolysis in this process. <b>Methods:</b> We investigated the role of glutaminolysis in myeloma cell growth. In addition, we analyzed the ability of CB-839 (telaglenastat), a glutaminase (GLS) inhibitor, to suppress myeloma cell proliferation and enhance the sensitivity to histone deacetylase (HDAC) inhibitors. <b>Results:</b> Glutamate deprivation significantly reduced MM cell proliferation. We observed an upregulation of GLS1 expression in MM cell lines compared to that in normal controls. CB-839 inhibits MM cell proliferation in a dose-dependent manner, resulting in enhanced cytotoxicity. Additionally, intracellular α-ketoglutarate and nicotinamide adenine dinucleotide phosphate levels decreased after CB-839 administration. Combining panobinostat with CB-839 resulted in enhanced cytotoxicity and increased caspase 3/7 activity. Cells transfected with GLS shRNA exhibited reduced cell viability and elevated sub-G1 phase according to cell cycle analysis results. Compared to control cells, these cells also showed increased sensitivity to panobinostat. <b>Conclusion:</b> Glutaminolysis contributes to the viability of MM cells, and the GLS inhibitor CB-839 has been proven to be an effective treatment for enhancing the cytotoxic effect of HDAC inhibition. These results are clinically relevant and suggest that CB-839 is a potential therapeutic candidate for patients with MM.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"7 ","pages":"25"},"PeriodicalIF":4.6,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The increasing prevalence of cancer drug resistance not only critically limits the efficiency of traditional therapies but also causes relapses or recurrences of cancer. Consequently, there remains an urgent need to address the intricate landscape of drug resistance beyond traditional cancer therapies. Recently, nanotechnology has played an important role in the field of various drug delivery systems for the treatment of cancer, especially therapy-resistant cancer. Among advanced nanomedicine technologies, lipid-based nanomaterials have emerged as effective drug carriers for cancer treatment, significantly improving therapeutic effects. Due to their biocompatibility, simplicity of preparation, and potential for functionalization, lipid-based nanomaterials are considered powerful competitors for resistant cancer. In this review, an overview of lipid-based nanomaterials for addressing cancer resistance is discussed. We summarize the recent progress in overcoming drug resistance in cancer by these lipid-based nanomaterials, and highlight their potential in future applications to reverse cancer resistance.
{"title":"Recent advanced lipid-based nanomedicines for overcoming cancer resistance.","authors":"Piroonrat Dechbumroong, Runjing Hu, Wisawat Keaswejjareansuk, Katawut Namdee, Xing-Jie Liang","doi":"10.20517/cdr.2024.19","DOIUrl":"https://doi.org/10.20517/cdr.2024.19","url":null,"abstract":"<p><p>The increasing prevalence of cancer drug resistance not only critically limits the efficiency of traditional therapies but also causes relapses or recurrences of cancer. Consequently, there remains an urgent need to address the intricate landscape of drug resistance beyond traditional cancer therapies. Recently, nanotechnology has played an important role in the field of various drug delivery systems for the treatment of cancer, especially therapy-resistant cancer. Among advanced nanomedicine technologies, lipid-based nanomaterials have emerged as effective drug carriers for cancer treatment, significantly improving therapeutic effects. Due to their biocompatibility, simplicity of preparation, and potential for functionalization, lipid-based nanomaterials are considered powerful competitors for resistant cancer. In this review, an overview of lipid-based nanomaterials for addressing cancer resistance is discussed. We summarize the recent progress in overcoming drug resistance in cancer by these lipid-based nanomaterials, and highlight their potential in future applications to reverse cancer resistance.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"7 ","pages":"24"},"PeriodicalIF":4.6,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-30eCollection Date: 2024-01-01DOI: 10.20517/cdr.2023.158
Bernhard Biersack, Michael Höpfner
Decades ago, the viral myeloblastosis oncogene v-myb was identified as a gene responsible for the development of avian leukemia. However, the relevance of MYB proteins for human cancer diseases, in particular for solid tumors, remained basically unrecognized for a very long time. The human family of MYB transcription factors comprises MYB (c-MYB), MYBL2 (b-MYB), and MYBL1 (a-MYB), which are overexpressed in several cancers and are associated with cancer progression and resistance to anticancer drugs. In addition to overexpression, the presence of activated MYB-fusion proteins as tumor drivers was described in certain cancers. The identification of anticancer drug resistance mediated by MYB proteins and their underlying mechanisms are of great importance in understanding failures of current therapies and establishing new and more efficient therapy regimens. In addition, new drug candidates targeting MYB transcription factor activity and signaling have emerged as a promising class of potential anticancer therapeutics that could tackle MYB-dependent drug-resistant cancers in a more selective way. This review describes the correlation of MYB transcription factors with the formation and persistence of cancer resistance to various approved and investigational anticancer drugs.
{"title":"Emerging role of MYB transcription factors in cancer drug resistance.","authors":"Bernhard Biersack, Michael Höpfner","doi":"10.20517/cdr.2023.158","DOIUrl":"10.20517/cdr.2023.158","url":null,"abstract":"<p><p>Decades ago, the viral myeloblastosis oncogene <i>v</i>-<i>myb</i> was identified as a gene responsible for the development of avian leukemia. However, the relevance of MYB proteins for human cancer diseases, in particular for solid tumors, remained basically unrecognized for a very long time. The human family of MYB transcription factors comprises MYB (c-MYB), MYBL2 (b-MYB), and MYBL1 (a-MYB), which are overexpressed in several cancers and are associated with cancer progression and resistance to anticancer drugs. In addition to overexpression, the presence of activated MYB-fusion proteins as tumor drivers was described in certain cancers. The identification of anticancer drug resistance mediated by MYB proteins and their underlying mechanisms are of great importance in understanding failures of current therapies and establishing new and more efficient therapy regimens. In addition, new drug candidates targeting MYB transcription factor activity and signaling have emerged as a promising class of potential anticancer therapeutics that could tackle MYB-dependent drug-resistant cancers in a more selective way. This review describes the correlation of MYB transcription factors with the formation and persistence of cancer resistance to various approved and investigational anticancer drugs.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"7 ","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-29eCollection Date: 2024-01-01DOI: 10.20517/cdr.2024.11
Huilan Zeng, Wei Wang, Lin Zhang, Zhenghong Lin
Human epidermal growth factor receptor 3 (HER3), which is part of the HER family, is aberrantly expressed in various human cancers. Since HER3 only has weak tyrosine kinase activity, when HER3 ligand neuregulin 1 (NRG1) or neuregulin 2 (NRG2) appears, activated HER3 contributes to cancer development and drug resistance by forming heterodimers with other receptors, mainly including epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Inhibition of HER3 and its downstream signaling, including PI3K/AKT, MEK/MAPK, JAK/STAT, and Src kinase, is believed to be necessary to conquer drug resistance and improve treatment efficiency. Until now, despite multiple anti-HER3 antibodies undergoing preclinical and clinical studies, none of the HER3-targeted therapies are licensed for utilization in clinical cancer treatment because of their safety and efficacy. Therefore, the development of HER3-targeted drugs possessing safety, tolerability, and sensitivity is crucial for clinical cancer treatment. This review summarizes the progress of the mechanism of HER3 in drug resistance, the HER3-targeted therapies that are conducted in preclinical and clinical trials, and some emerging molecules that could be used as future designed drugs for HER3, aiming to provide insights for future research and development of anticancer drugs targeting HER3.
{"title":"HER3-targeted therapy: the mechanism of drug resistance and the development of anticancer drugs.","authors":"Huilan Zeng, Wei Wang, Lin Zhang, Zhenghong Lin","doi":"10.20517/cdr.2024.11","DOIUrl":"10.20517/cdr.2024.11","url":null,"abstract":"<p><p>Human epidermal growth factor receptor 3 (HER3), which is part of the HER family, is aberrantly expressed in various human cancers. Since HER3 only has weak tyrosine kinase activity, when HER3 ligand neuregulin 1 (NRG1) or neuregulin 2 (NRG2) appears, activated HER3 contributes to cancer development and drug resistance by forming heterodimers with other receptors, mainly including epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Inhibition of HER3 and its downstream signaling, including PI3K/AKT, MEK/MAPK, JAK/STAT, and Src kinase, is believed to be necessary to conquer drug resistance and improve treatment efficiency. Until now, despite multiple anti-HER3 antibodies undergoing preclinical and clinical studies, none of the HER3-targeted therapies are licensed for utilization in clinical cancer treatment because of their safety and efficacy. Therefore, the development of HER3-targeted drugs possessing safety, tolerability, and sensitivity is crucial for clinical cancer treatment. This review summarizes the progress of the mechanism of HER3 in drug resistance, the HER3-targeted therapies that are conducted in preclinical and clinical trials, and some emerging molecules that could be used as future designed drugs for HER3, aiming to provide insights for future research and development of anticancer drugs targeting HER3.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"7 ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Globally, cancer, as a major public health concern, poses a severe threat to people's well-being. Advanced and specialized therapies can now cure the majority of people with early-stage cancer. However, emerging resistance to traditional and novel chemotherapeutic drugs remains a serious issue in clinical medicine. Chemoresistance often leads to cancer recurrence, metastasis, and increased mortality, accounting for 90% of chemotherapy failures. Thus, it is important to understand the molecular mechanisms of chemoresistance and find novel therapeutic approaches for cancer treatment. Among the several factors responsible for chemoresistance, calcium (Ca2+) dysregulation plays a significant role in cancer progression and chemoresistance. Therefore, targeting this derailed Ca2+ signalling for cancer therapy has become an emerging research area. Of note, the Ca2+ signal and its proteins are a multifaceted and potent tool by which cells achieve specific outcomes. Depending on cell survival needs, Ca2+ is either upregulated or downregulated in both chemosensitive and chemoresistant cancer cells. Consequently, the appropriate treatment should be selected based on Ca2+ signalling dysregulation. This review discusses the role of Ca2+ in cancer cells and the targeting of Ca2+ channels, pumps, and exchangers. Furthermore, we have emphasised the role of Ca2+ in chemoresistance and therapeutic strategies. In conclusion, targeting Ca2+ signalling is a multifaceted process. Methods such as site-specific drug delivery, target-based drug-designing, and targeting two or more Ca2+ proteins simultaneously may be explored; however, further clinical studies are essential to validate Ca2+ blockers' anti-cancer efficacy.
{"title":"Dysregulation of calcium homeostasis in cancer and its role in chemoresistance.","authors":"Neema Kumari, Narasimha Pullaguri, Subha Narayan Rath, Ashish Bajaj, Vikas Sahu, Kranti Kiran Reddy Ealla","doi":"10.20517/cdr.2023.145","DOIUrl":"10.20517/cdr.2023.145","url":null,"abstract":"<p><p>Globally, cancer, as a major public health concern, poses a severe threat to people's well-being. Advanced and specialized therapies can now cure the majority of people with early-stage cancer. However, emerging resistance to traditional and novel chemotherapeutic drugs remains a serious issue in clinical medicine. Chemoresistance often leads to cancer recurrence, metastasis, and increased mortality, accounting for 90% of chemotherapy failures. Thus, it is important to understand the molecular mechanisms of chemoresistance and find novel therapeutic approaches for cancer treatment. Among the several factors responsible for chemoresistance, calcium (Ca<sup>2+</sup>) dysregulation plays a significant role in cancer progression and chemoresistance. Therefore, targeting this derailed Ca<sup>2+</sup> signalling for cancer therapy has become an emerging research area. Of note, the Ca<sup>2+</sup> signal and its proteins are a multifaceted and potent tool by which cells achieve specific outcomes. Depending on cell survival needs, Ca<sup>2+</sup> is either upregulated or downregulated in both chemosensitive and chemoresistant cancer cells. Consequently, the appropriate treatment should be selected based on Ca<sup>2+</sup> signalling dysregulation. This review discusses the role of Ca<sup>2+</sup> in cancer cells and the targeting of Ca<sup>2+</sup> channels, pumps, and exchangers. Furthermore, we have emphasised the role of Ca<sup>2+</sup> in chemoresistance and therapeutic strategies. In conclusion, targeting Ca<sup>2+</sup> signalling is a multifaceted process. Methods such as site-specific drug delivery, target-based drug-designing, and targeting two or more Ca<sup>2+</sup> proteins simultaneously may be explored; however, further clinical studies are essential to validate Ca<sup>2+</sup> blockers' anti-cancer efficacy.</p>","PeriodicalId":70759,"journal":{"name":"癌症耐药(英文)","volume":"7 ","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}