Anti-Cancer Drugs最新文献_第3页

Enhancing the management of locally advanced head and neck malignancies and cases with local/neck recurrence and metastasis through the integration of anlotinib with concurrent radiochemotherapy. 通过将安洛替尼与同期放化疗相结合，加强对局部晚期头颈部恶性肿瘤以及局部/颈部复发和转移病例的治疗。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-05-27 DOI: 10.1097/CAD.0000000000001621

Xiaojing Tie, Hang Li, Ling Gao, Peijie Liu, Yaohong Gao, Mingxin Jin, Guangting Duan, Zhenying Yi

{"title":"Enhancing the management of locally advanced head and neck malignancies and cases with local/neck recurrence and metastasis through the integration of anlotinib with concurrent radiochemotherapy.","authors":"Xiaojing Tie, Hang Li, Ling Gao, Peijie Liu, Yaohong Gao, Mingxin Jin, Guangting Duan, Zhenying Yi","doi":"10.1097/CAD.0000000000001621","DOIUrl":"10.1097/CAD.0000000000001621","url":null,"abstract":"The aim of this study is to assess the effectiveness and safety of anlotinib in conjunction with concurrent radiochemotherapy for the treatment of locally advanced head and neck malignant tumors, including cases exhibiting local or neck recurrence and metastasis. Between June 2020 and June 2023, 42 patients diagnosed with locally advanced head and neck malignant tumors or presenting with local or neck recurrence and metastasis were recruited. These individuals received treatment that combined anlotinib with concurrent radiochemotherapy, followed by a minimum of two cycles of oral anlotinib upon completion of the initial treatment regimen. Among the 19 patients diagnosed with nasopharyngeal carcinoma, 14 patients attained a complete response, while four patients achieved partial response, resulting in an overall response rate of 94.74% (18/19). Conversely, among the 23 patients with non-nasopharyngeal carcinoma, two patients achieved complete response and 16 attained partial response, yielding a response rate of 78.26% (18/23). The 6-month progression-free survival rate was 95.24%. After treatment, serum vascular endothelial growth factor receptor levels exhibited a significant decrease compared with pretreatment levels. Notably, no instances of treatment-related serious adverse reactions were recorded. The combination of anlotinib with concurrent radiochemotherapy demonstrates favorable efficacy in managing locally advanced head and neck malignant tumors, including instances of local or neck recurrence and metastasis. Furthermore, the treatment regimen is characterized by an acceptable safety profile and tolerability.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Study on the therapeutic effect of sintilimab combined with modified DCF regimen on advanced gastric cancer and its impact on Th1/Th2 immune balance. 研究辛替利马联合改良 DCF 方案对晚期胃癌的疗效及其对 Th1/Th2 免疫平衡的影响。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-06-28 DOI: 10.1097/CAD.0000000000001629

Lili Cai, Lan Qu, Yanjie Cheng, Jinfeng Zhang, Shiying Li, Shenghong Wu

{"title":"Study on the therapeutic effect of sintilimab combined with modified DCF regimen on advanced gastric cancer and its impact on Th1/Th2 immune balance.","authors":"Lili Cai, Lan Qu, Yanjie Cheng, Jinfeng Zhang, Shiying Li, Shenghong Wu","doi":"10.1097/CAD.0000000000001629","DOIUrl":"10.1097/CAD.0000000000001629","url":null,"abstract":"The aim of this study was to observe the therapeutic effect of sintilimab combined with a modified docetaxel + cisplatin + fluorouracil (DCF) regimen on advanced gastric cancer and its effect on Th1/Th2 immune balance. Ninety-eight cases of advanced gastric cancer patients who visited our hospital from April 2020 to May 2022 were selected and divided into 48 cases each in the conventional group and the research group by random number table method; the DCF regimen was adopted in the conventional group, and sintilimab combined with modified DCF regimen was adopted in the research group, and the therapeutic effects of the patients in the two groups and the changes of Th1/Th2 immune indexes were compared. CEA, CA199, CA242, CD168 AQ3, and IL-4 in the study group were lower than those in the conventional group at the end of three cycles of treatment, and the difference was statistically significant ( P < 0.001). The levels of IFN-γ and IL-4 in the study group at the end of three cycles of treatment were higher than those in the conventional group ( P < 0.001). The incidence of adverse reactions during treatment in the study group was lower than that in the conventional group ( P < 0.001), and the grading of adverse reactions in the study group was milder than that in the conventional group. Sintilimab combined with a modified DCF regimen in the treatment of advanced gastric cancer not only improves the therapeutic effect but also positively affects the Th1/Th2 immune balance, which provides better immune regulation for patients with advanced gastric cancer.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

First case report of sunvozertinib for the treatment of HER2 exon 20 insertion in lung adenocarcinoma. 舒伐他尼治疗肺腺癌 HER2 20 外显子插入的首个病例报告。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-06-26 DOI: 10.1097/CAD.0000000000001628

Tao Luan, Xinqing Lin, Xiaohong Xie, Gang Yang, Shuaiying Wang, Jianqing Hao, Chengzhi Zhou

{"title":"First case report of sunvozertinib for the treatment of HER2 exon 20 insertion in lung adenocarcinoma.","authors":"Tao Luan, Xinqing Lin, Xiaohong Xie, Gang Yang, Shuaiying Wang, Jianqing Hao, Chengzhi Zhou","doi":"10.1097/CAD.0000000000001628","DOIUrl":"10.1097/CAD.0000000000001628","url":null,"abstract":"Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. It is generally considered as a poor prognostic marker. Targeted therapies, such as small molecule tyrosine kinase inhibitors (TKIs), showed limited efficacy in HER2-mutant advanced nonsmall cell lung cancer (NSCLC). In the 2023 National Comprehensive Cancer Network guidelines for NSCLC, antibody-drug conjugate trastuzumab emtansine is recommended for the treatment of HER2-mutant lung cancer. However, this medication is currently not approved in certain regions. So it is necessary to explore alternative treatment options for HER2-mutant NSCLC patients. In our study of a patient with HER2 exon 20 insertion lung adenocarcinoma who had previously failed multiple epidermal growth factor receptor (EGFR)-TKI treatments, we discovered that sunvozertinib could stabilize the patient's condition, achieving a progression-free survival of 87 days. This is a novel finding that may provide new treatment options for HER2 exon 20 insertion patients who have failed TKI therapy.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptome and metabolome sequencing identifies glutamate and LPAR1 as potential factors of anlotinib resistance in thyroid cancer. 转录组和代谢组测序发现谷氨酸和LPAR1是甲状腺癌患者对安罗替尼耐药的潜在因素。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-05-31 DOI: 10.1097/CAD.0000000000001626

Bin Liu, Ying Peng, Yanjun Su, Chang Diao, Jun Qian, Xiangxiang Zhan, Ruochuan Cheng

{"title":"Transcriptome and metabolome sequencing identifies glutamate and LPAR1 as potential factors of anlotinib resistance in thyroid cancer.","authors":"Bin Liu, Ying Peng, Yanjun Su, Chang Diao, Jun Qian, Xiangxiang Zhan, Ruochuan Cheng","doi":"10.1097/CAD.0000000000001626","DOIUrl":"10.1097/CAD.0000000000001626","url":null,"abstract":"Objective: To explore the mechanism of anlotinib resistance in thyroid carcinoma.Methods: We constructed an anlotinib-resistant thyroid carcinoma cell line and observed the effect of drug resistance on the functional activity of these cell lines. Transcriptome sequencing and metabolomic sequencing combined with biosynthesis analysis were used to explore and screen possible drug resistance regulatory pathways.Results: Through transcriptomic sequencing analysis of drug-resistant cell lines, it was found that the differentially expressed genes of drug-resistant strains were enriched mainly in the interleukin 17, transforming growth factor-β, calcium, peroxisome proliferator activated receptor, and other key signaling pathways. A total of 354 differentially expressed metabolic ions were screened using liquid chromatography-mass spectrometry/mass spectrometry to determine the number of metabolic ions in the drug-resistant strains. The results of the Venn diagram correlation analysis showed that glutamate is closely related to multiple pathways and may be an important regulatory factor of anlotinib resistance in thyroid carcinoma. In addition, eight common differentially expressed genes were screened by comparing the gene expression profiling interactive analysis database and sequencing results. Further quantitative real time polymerase chain reaction verification, combined with reports in the literature, showed that LPAR1 may be an important potential target.Conclusion: This is the first study in which the drug resistance of thyroid cancer to anlotinib was preliminarily discussed. We confirmed that anlotinib resistance in thyroid cancer promotes the progression of malignant biological behavior. We conclude that glutamate may be a potential factor for anlotinib resistance in thyroid cancer and that LPAR1 is also a potentially important target.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combating anoikis resistance: bioactive compounds transforming prostate cancer therapy. 对抗抗药性：生物活性化合物改变前列腺癌疗法。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-05-14 DOI: 10.1097/CAD.0000000000001616

Shweta Gulia, Prakash Chandra, Asmita Das

{"title":"Combating anoikis resistance: bioactive compounds transforming prostate cancer therapy.","authors":"Shweta Gulia, Prakash Chandra, Asmita Das","doi":"10.1097/CAD.0000000000001616","DOIUrl":"10.1097/CAD.0000000000001616","url":null,"abstract":"The study aims to discuss the challenges associated with treating prostate cancer (PCa), which is known for its complexity and drug resistance. It attempts to find differentially expressed genes (DEGs), such as those linked to anoikis resistance and circulating tumor cells, in PCa samples. This study involves analyzing the functional roles of these DEGs using gene enrichment analysis, and then screening of 102 bioactive compounds to identify a combination that can control the expression of the identified DEGs. In this study, 53 DEGs were identified from PCa samples including anoikis-resistant PCa cells and circulating tumor cells in PCa. Gene enrichment analysis with regards to functional enrichment of DEGs was performed. An inclusive screening process was carried out among 102 bioactive compounds to identify a combination capable of affecting and regulating the expression of selected DEGs. Eventually, gastrodin, nitidine chloride, chenodeoxycholic acid, and bilobalide were selected, as their combination demonstrated ability to modulate expression of 50 out of the 53 genes targeted. The subsequent analysis focused on investigating the biological pathways and processes influenced by this combination. The findings revealed a multifaceted and multidimensional approach to tumor regression. The combination of bioactive compounds exhibited effects on various genes including those related to production of inflammatory cytokines, cell proliferation, autophagy, apoptosis, angiogenesis, and metastasis. The current study has made a valuable contribution to the development of a combination of bioactive natural compounds that can significantly impede the development of treatment resistance in prostate tumor while countering the tumors' evasion of the immune system. The implications of this study are highly significant as it suggests the creation of an enhanced immunotherapeutic, natural therapeutic concoction with combinatorial potential.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HER2 exon 20 mutant non-small cell lung cancer with complete remission of intracranial metastases with trastuzumab deruxtecan: a case report. HER2 20 号外显子突变的非小细胞肺癌，曲妥珠单抗德鲁司坦治疗后颅内转移完全缓解：病例报告。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-05-16 DOI: 10.1097/CAD.0000000000001625

Ali Kaan Güren, Erkam Kocaaslan, Yeşim Ağyol, Nargiz Majidova, Nadiye Sever, Pinar Erel, Abdussamet Çelebi, Rukiye Arikan, Selver Işik, Murat Sari, İbrahim Vedat Bayoğlu, Osman Köstek

{"title":"HER2 exon 20 mutant non-small cell lung cancer with complete remission of intracranial metastases with trastuzumab deruxtecan: a case report.","authors":"Ali Kaan Güren, Erkam Kocaaslan, Yeşim Ağyol, Nargiz Majidova, Nadiye Sever, Pinar Erel, Abdussamet Çelebi, Rukiye Arikan, Selver Işik, Murat Sari, İbrahim Vedat Bayoğlu, Osman Köstek","doi":"10.1097/CAD.0000000000001625","DOIUrl":"10.1097/CAD.0000000000001625","url":null,"abstract":"Trastuzumab deruxtecan (T-DXd) is a novel anti-HER2 antibody-drug conjugate formed by the combination of trastuzumab and deruxtecan. It is used in human epidermal growth factor 2 receptor (HER2) mutant breast, stomach and colorectal cancers as well as non-small cell lung cancer (NSCLC). The 58-year-old denovo metastatic NSCLC patient we will discuss here progressed with newly developing brain metastasis under first-line carboplatin/paclitaxel treatment. After next generation sequencing revealed a mutation in the ERBB2 gene located in exon 20, we administered T-DXd to our patient. While a significant improvement was observed in the clinical condition of the patient after one course of treatment, brain metastases were found to be in complete response in control screening after four courses of treatment. Systemic screening with PET/computed tomography showed nearly complete regression of the primary lesion, metastatic lymphadenopathies, and surrenal metastases. T-DXd may be successfully used in HER2 mutant metastatic NSCLC patients. In addition, it can also be successfully used in patients with central nervous system metastases with or without cranial radiotherapy.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EP-0108A is a moderation selectively BRD4 BD2 inhibitor with potential AML tumor suppression. EP-0108A 是一种适度选择性 BRD4 BD2 抑制剂，具有抑制急性髓细胞性白血病肿瘤的潜力。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-08-28 DOI: 10.1097/CAD.0000000000001655

Li Li, Hui Zhu, Shuang Liu

{"title":"EP-0108A is a moderation selectively BRD4 BD2 inhibitor with potential AML tumor suppression.","authors":"Li Li, Hui Zhu, Shuang Liu","doi":"10.1097/CAD.0000000000001655","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001655","url":null,"abstract":"Acute myeloid leukemia is the most common type of acute leukemia in adults. The epigenetic molecule BRD4 is a member of the bromodomain and extra-terminal family and plays an important role in the occurrence and development of tumors. BRD4 is essential for oncogene expression, including c-Myc. So, BRD4 inhibition is considered as an effective strategy for the treatment of hematological and solid malignancies. In recent years, several small molecule inhibitors targeting BRD4 have been developed. However, these inhibitors had excessive hematological toxicity due to the lack of specific binding to BD1 and BD2 domains of BRD4, while other inhibitors with high selectivity lose their antitumor efficacy. To balance the relationship between efficacy and safety, we developed EP-0108A, a BRD4 inhibitor with moderate selectivity for the BD2 domain over BD1 domain of BRD4. Our results show that EP-0108A has antitumor effects in MV4-11 and Kasumi-1 cell line-derived xenograft mouse models without significant effects on heart or breathing safe in rats and Beagle dogs. In repeated dose toxicity studies, EP-0108A showed reversible hematological and gastrointestinal toxicity in both rats and dogs. Our findings indicate that EP-0108A has the potential to be a new therapeutic agent for the treatment of cancer.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergistic combination effect of the PCA-1/ALKBH3 inhibitor HUHS015 on prostate cancer drugs in vitro and in vivo. PCA-1/ALKBH3 抑制剂 HUHS015 在体外和体内对前列腺癌药物的协同组合效应。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-08-26 DOI: 10.1097/CAD.0000000000001656

Miyuki Mabuchi, Kazutake Tsujikawa, Akito Tanaka

{"title":"Synergistic combination effect of the PCA-1/ALKBH3 inhibitor HUHS015 on prostate cancer drugs in vitro and in vivo.","authors":"Miyuki Mabuchi, Kazutake Tsujikawa, Akito Tanaka","doi":"10.1097/CAD.0000000000001656","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001656","url":null,"abstract":"Prostate cancer antigen-1/ALKBH3, a DNA/RNA demethylase of 3-methylcytosine, 1-methyladenine (1-meA), and 6-meA, was found in prostate cancer as an important prognostic factor. Additionally, 1-meA has been associated with other cancers. The ALKBH3 inhibitor HUHS015 was found to be effective against prostate cancer both in vitro and in vivo. Herein, we investigated the effect of HUHS015 in combination with drugs for prostate cancer approved in Japan (including bicalutamide, cisplatin, mitoxantrone, prednisolone, ifosfamide, tegafur/uracil, docetaxel, dacarbazine, and estramustine) by treating DU145 cells with around IC50 value concentrations of these drugs for 3 days. Additionally, the cells were observed for additional 9 days after drug removal. Combination treatment with dacarbazine, estramustine, tegafur/uracil, and HUHS015 showed a slight additive effect after 3 days. After drug washout of them and mitoxantrone, the combined effects and levels were enhanced and sustained, although the effects of each treatment alone declined. HUHS015 combined with cisplatin or docetaxel elicited synergistic and sustained effects. In vivo, combining HUHS015 and docetaxel, the first chemotherapeutic agent for castration-resistant prostate cancer, showed notable effects in the DU145 xenograft model. In conclusion, HUHS015 exhibited a synergistic effect with docetaxel and drugs acting on DNA in vitro, even after drug removal. Since cancer chemotherapy is typically administered during rest periods due to its high toxicity, combining it with an ALKBH3 inhibitor could be a promising strategy for enhancing cancer treatment, as it can elicit an additive effect during treatment, allowing dosage reduction, and synergistically sustain the effect after drug washout during rest periods.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Screening of a kinase inhibitor library identified novel targetable kinase pathways in triple-negative breast cancer. 对激酶抑制剂库进行筛选，发现了三阴性乳腺癌中新的可靶向激酶通路。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-08-21 DOI: 10.1097/CAD.0000000000001658

Caroline H Rinderle, Christopher V Baker, Courtney B Lagarde, Khoa Nguyen, Sara Al-Ghadban, Margarite D Matossian, Van T Hoang, Elizabeth C Martin, Bridgette M Collins-Burow, Simak Ali, David H Drewry, Matthew E Burow, Bruce A Bunnell

{"title":"Screening of a kinase inhibitor library identified novel targetable kinase pathways in triple-negative breast cancer.","authors":"Caroline H Rinderle, Christopher V Baker, Courtney B Lagarde, Khoa Nguyen, Sara Al-Ghadban, Margarite D Matossian, Van T Hoang, Elizabeth C Martin, Bridgette M Collins-Burow, Simak Ali, David H Drewry, Matthew E Burow, Bruce A Bunnell","doi":"10.1097/CAD.0000000000001658","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001658","url":null,"abstract":"Triple-negative breast cancer (TNBC) is a highly invasive breast cancer subtype that is challenging to treat due to inherent heterogeneity and absence of estrogen, progesterone, and human epidermal growth factor 2 receptors. Kinase signaling networks drive cancer growth and development, and kinase inhibitors are promising anti-cancer strategies in diverse cancer subtypes. Kinase inhibitor screens are an efficient, valuable means of identifying compounds that suppress cancer cell growth in vitro, facilitating the identification of kinase vulnerabilities to target therapeutically. The Kinase Chemogenomic Set is a well-annotated library of 187 kinase inhibitor compounds that indexes 215 kinases of the 518 in the known human kinome representing various kinase networks and signaling pathways, several of which are understudied. Our screen revealed 14 kinase inhibitor compounds effectively inhibited TNBC cell growth and proliferation. Upon further testing, three compounds, THZ531, THZ1, and PFE-PKIS 29, had the most significant and consistent effects across a range of TNBC cell lines. These cyclin-dependent kinase (CDK)12/CDK13, CDK7, and phosphoinositide 3-kinase inhibitors, respectively, decreased metabolic activity in TNBC cell lines and promote a gene expression profile consistent with the reversal of the epithelial-to-mesenchymal transition, indicating these kinase networks potentially mediate metastatic behavior. These data identified novel kinase targets and kinase signaling pathways that drive metastasis in TNBC.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential functionality of fluoropyrimidine nucleosides for safe cancer therapy. 氟嘧啶核苷的不同功能可安全治疗癌症。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-08-20 DOI: 10.1097/CAD.0000000000001644

Tim Holzinger, Julia Frei, Natalia Teresa Jarzebska, Hans-Dietmar Beer, Thomas M Kündig, Steve Pascolo, Severin Läuchli, Mark Mellett

{"title":"Differential functionality of fluoropyrimidine nucleosides for safe cancer therapy.","authors":"Tim Holzinger, Julia Frei, Natalia Teresa Jarzebska, Hans-Dietmar Beer, Thomas M Kündig, Steve Pascolo, Severin Läuchli, Mark Mellett","doi":"10.1097/CAD.0000000000001644","DOIUrl":"10.1097/CAD.0000000000001644","url":null,"abstract":"Chemotherapies are standard care for most cancer types. Pyrimidine analogs including 5-fluorouracil, cytosine arabinoside, 5-azacytidine, and gemcitabine are effective drugs that are utilized as part of a number of anticancer regimens. However, their lack of cell-specificity results in severe side effects. Therefore, there is a capacity to improve the efficacy of such therapies, while decreasing unwanted side effects. Here, we report that while 5-fluorocytosine is not chemotherapeutic in itself, incorporated into a ribonucleoside and more importantly into an RNA oligonucleotide, it induces cytotoxic effects on cancer cells in vitro . Interestingly, these effects are rescued by both uridine and thymidine. Similarly, in-vitro 2'-deoxy-5-fluorocytidine inhibits the growth of tumor cells but has the advantage of being less toxic to human primary cells compared with 5-fluorocytidine, suggesting that the deoxyribonucleoside could exhibit less side-effects in vivo . Thus, this work indicates that the potency of 5-fluorocytidine and 2'-deoxy-5-fluorocytidine should be further explored. In particular, oligonucleotides incorporating 5-fluorocytosine could be novel chemotherapeutic drugs that could be formulated in cancer-specific particles for safe and efficacious cancer treatments.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0