Anti-Cancer Drugs最新文献_第10页

Combination of anlotinib and sintilimab for the treatment of recurrent or metastatic head and neck squamous cell carcinoma: a single-arm prospective study. anlotinib和sintilmab联合治疗复发或转移性头颈部鳞状细胞癌：单臂前瞻性研究

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-12-11 DOI: 10.1097/CAD.0000000000001660

Tianxiao Wang, Jiaxin Wang, Yabing Zhang, Yuntao Song, Guohui Xu, Bin Zhang

{"title":"Combination of anlotinib and sintilimab for the treatment of recurrent or metastatic head and neck squamous cell carcinoma: a single-arm prospective study.","authors":"Tianxiao Wang, Jiaxin Wang, Yabing Zhang, Yuntao Song, Guohui Xu, Bin Zhang","doi":"10.1097/CAD.0000000000001660","DOIUrl":"10.1097/CAD.0000000000001660","url":null,"abstract":"To investigate whether blocking both programmed cell death protein and vascular endothelial growth factor receptor could offer superior anticancer activity in these patients without compromising safety. In this study, patients were administered oral anlotinib (12 mg/day) on days 1-14 and intravenous sintilimab (200 mg) on day 1 of a 3-weekly cycle. The primary endpoints included the objective response rate and disease control rate. The secondary endpoints included overall survival (OS) and safety. Ten eligible patients were enrolled between June 2019 and May 2022, and eight patients underwent radiographic assessments. The results showed an objective response rate of 50% (partial and complete response in four and zero patients, respectively) and a disease control rate of 100%; four patients demonstrated stable disease for at least 8 weeks. The median OS was 4.37 (in our study, the score was 7), and the OS rate at 12 months was 37.5%. The Kaplan-Meier survival curve showed that the group with high blood glucose levels had a significantly shorter duration of survival than those with normal blood glucose levels. Adverse events of grade 3 and higher occurred in 50% of patients, and the most common severe adverse events included tumor pain (50%), hypertension (37.5%), tumor hemorrhage (25%), and decreased appetite (25%). The combination of anlotinib and sintilimab showed promising efficacy in controlling tumor size. However, the disappointing OS rate suggests that anti-vascular endothelial growth factor receptor agents should be used cautiously after radical radiation therapy. The combination used in this study demonstrated a toxicity profile comparable to that of other agents used in this setting. These findings warrant further investigation into the potential clinical utility of this combination.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":"36 1","pages":"79-84"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821762","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

Screening of a kinase inhibitor library identified novel targetable kinase pathways in triple-negative breast cancer. 激酶抑制剂文库的筛选在三阴性乳腺癌中发现了新的靶向激酶途径。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub 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":"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":"36 1","pages":"39-48"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821722","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

Research on curcumin mediating immunotherapy of colorectal cancer by regulating cancer associated fibroblasts. 姜黄素通过调节癌症相关成纤维细胞介导结直肠癌免疫疗法的研究。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-10-17 DOI: 10.1097/CAD.0000000000001659

Chenliang Hou, Yanning Hu, Tao Zhang

{"title":"Research on curcumin mediating immunotherapy of colorectal cancer by regulating cancer associated fibroblasts.","authors":"Chenliang Hou, Yanning Hu, Tao Zhang","doi":"10.1097/CAD.0000000000001659","DOIUrl":"10.1097/CAD.0000000000001659","url":null,"abstract":"The objective was to investigate curcumin's (Cur) function and associated molecular mechanisms in regulating tumor immunity in colon cancer. Primary cancer-associated fibroblasts (CAFs) from mouse CT26 colon cancer tumors were isolated. Validation of primary CAFs using immunofluorescence assay was done. Cell Counting Kit-8 experiments, real-time quantitative PCR (qPCR), and enzyme linked immunosorbent assay experiments were conducted to investigate how curcumin affected the growth and cytokine secretion functions of CAFs. The effect of curcumin on regulating PD-L1 expression on CT26 cells through CAFs in vitro was explored through coculture of CAFs and tumor cells, qPCR, and western blot experiments. A mouse colon cancer cell model was established in Balb/c nude mice to explore the effect of curcumin on colon tumor cells. Changes in the tumor microenvironment were detected by flow cytometry to explore the synergistic effect of curcumin combined with anti-PD-1 monoclonal antibody in the treatment of mouse colon cancer. In vitro, curcumin prevented the growth and TGF-β secretion of CT26 cells. At the same time, curcumin inhibited the secretion of TGF-β by CAFs, thereby downregulating the PD-L1 expression of CT26 cells. In vivo, curcumin combined with anti-PD-1 antibodies can further enhance the inhibitory effect of PD-1 antibodies on tumors and increase the number of tumor-suppressing immune cells in the tumor microenvironment, such as M1 macrophages and CD8 T cells, thus inhibiting tumors. Immune M2 macrophages, regulatory T cells, and other cells were reduced. In conclusion, curcumin reduces the expression of PD-L1 in colon cancer cells and improves the tumor immune microenvironment by inhibiting the proliferation of CAFs and the secretion of TGF-β. Curcumin and anti-PD-1 treatment have synergistic inhibitory effects on colon cancer.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"72-78"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279600","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 : 2025-01-01 Epub 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":"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 IC 50 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":" ","pages":"19-27"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","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

Holding the therapy in CLLp53: mechanisms to achieve durable responses. 在 CLLp53 中坚持治疗：实现持久应答的机制。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-08-09 DOI: 10.1097/CAD.0000000000001653

Rodrigo Cantera, Tatiana Fernández-Barge, Jon Salmanton-García, Lucrecia Yáñez

引用次数: 0

Machine learning-based integration develops a multiple programmed cell death signature for predicting the clinical outcome and drug sensitivity in colorectal cancer. 基于机器学习的整合开发出一种多程序细胞死亡特征，用于预测结直肠癌的临床结果和药物敏感性。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-08-09 DOI: 10.1097/CAD.0000000000001654

Chunhong Li, Yuhua Mao, Yi Liu, Jiahua Hu, Chunchun Su, Haiyin Tan, Xianliang Hou, Minglin Ou

{"title":"Machine learning-based integration develops a multiple programmed cell death signature for predicting the clinical outcome and drug sensitivity in colorectal cancer.","authors":"Chunhong Li, Yuhua Mao, Yi Liu, Jiahua Hu, Chunchun Su, Haiyin Tan, Xianliang Hou, Minglin Ou","doi":"10.1097/CAD.0000000000001654","DOIUrl":"10.1097/CAD.0000000000001654","url":null,"abstract":"Tumorigenesis and treatment are closely associated with various programmed cell death (PCD) patterns. However, the coregulatory role of multiple PCD patterns in colorectal cancer (CRC) remains unknown. In this study, we developed a multiple PCD index (MPCDI) based on 19 PCD patterns using two machine learning algorithms for risk stratification, prognostic prediction, construction of nomograms, immune cell infiltration analysis, and chemotherapeutic drug sensitivity analysis. As a result, in the TCGA-COAD, GSE17536, and GSE29621 cohorts, the MPCDI can effectively distinguished survival outcomes in CRC patients and served as an independent factor for CRC patients. We then explored the immune infiltration landscape in two groups using the nine algorithms and found more overall immune infiltration in the high-MPCDI group. TIDE scores suggested that the increased immune evasion potential and immune checkpoint inhibition therapy may be less effective in the high-MPCDI group. Immunophenoscores indicated that anti-PD1, anti-cytotoxic T-lymphocyte associated antigen 4 (anti-CTLA4), and anti-PD1-CTLA4 combination therapies are less effective in the high-MPCDI group. In addition, the high-MPCDI group was more sensitive to AZD1332, Foretinib, and IGF1R_3801, and insensitive to AZD3759, AZD5438, AZD6482, Erlotinib, GSK591, IAP_5620, and Picolinici-acid, which suggests that the MPCDI can guide drug selection for CRC patients. As a new clinical classifier, the MPCDI can more accurately distinguish CRC patients who benefit from immunotherapy and develop personalized treatment strategies for CRC patients.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"1-18"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915974","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

Utidelone plus pembrolizumab as the fourth-line combination treatment in non-small cell lung cancer with EGFR mutation: a case report. 表皮生长因子受体（EGFR）突变的非小细胞肺癌四线联合治疗病例报告：优替龙联合 pembrolizumab。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-10-18 DOI: 10.1097/CAD.0000000000001661

Henghu Fang, Wei Yang, Qing Han, Rugang Zhao, Wei Zheng, Zejun Lu, Shanshan Wu, Qi Zhu, Jingjiao Li, Gaowa Guan, Juyi Wen

{"title":"Utidelone plus pembrolizumab as the fourth-line combination treatment in non-small cell lung cancer with EGFR mutation: a case report.","authors":"Henghu Fang, Wei Yang, Qing Han, Rugang Zhao, Wei Zheng, Zejun Lu, Shanshan Wu, Qi Zhu, Jingjiao Li, Gaowa Guan, Juyi Wen","doi":"10.1097/CAD.0000000000001661","DOIUrl":"10.1097/CAD.0000000000001661","url":null,"abstract":"Utidelone is an ebomycin derivative chemotherapeutic drug, which can promote tubulin polymerization and stabilize microtubule structure, so as to induce apoptosis. The drug is an innovative drug independently developed by China with independent intellectual property rights. Phase II clinical trials for advanced breast cancer are being approved by National Medical Products Administration for the treatment of advanced breast cancer. However, there is no report on the application in non-small cell lung cancer (NSCLC) patients with the epidermal growth factor receptor (EGFR) mutation. This case is a patient with EGFR mutant stage IV NSCLC who has progressed after third-line targeted therapy. The fourth line was treated with utidelone combined with pabolizumab. The patient had progressed after targeted therapy with oxitinib, ametinib, and vometinib. Due to the patient's physical reasons, the traditional platinum drugs were not suitable, so the patient was treated with utidelone combined with pabolizumab. The curative effect was evaluated as SD after two cycles and progesterone receptor after four cycles. At present, it is still in the maintenance of reduction of utidelone combined with pabolizumab, and the tumor continues to shrink. Although peripheral neurotoxicity occurred during treatment, it improved after symptomatic treatment. The treatment of EGFR mutant stage IV NSCLC with utidelone combined with pabolizumab has good effect and mild adverse reactions.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"94-96"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456487","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

Pathological complete response achieved with FLOT chemotherapy in two patients with MSI-H esophagogastric junction and gastric adenocarcinoma. 两名 MSI-H 型食管胃交界处和胃腺癌患者接受 FLOT 化疗后获得病理完全缓解。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-08-09 DOI: 10.1097/CAD.0000000000001652

Federica Cosso, Daniele Lavacchi, Luca Messerini, Vittorio Briganti, Francesca Castiglione, Marco Brugia, Valentina Berti, Sara Fancelli, Fabio Cianchi, Agnese Vannini, Serena Pillozzi, Lorenzo Antonuzzo

{"title":"Pathological complete response achieved with FLOT chemotherapy in two patients with MSI-H esophagogastric junction and gastric adenocarcinoma.","authors":"Federica Cosso, Daniele Lavacchi, Luca Messerini, Vittorio Briganti, Francesca Castiglione, Marco Brugia, Valentina Berti, Sara Fancelli, Fabio Cianchi, Agnese Vannini, Serena Pillozzi, Lorenzo Antonuzzo","doi":"10.1097/CAD.0000000000001652","DOIUrl":"10.1097/CAD.0000000000001652","url":null,"abstract":"Globally, more than 1 million new cases of gastric cancer were estimated in 2020, ranking fourth in cancer mortality. Currently although in resectable gastric cancer and esophagogastric junction (EGJ) adenocarcinoma a perioperative triplet chemotherapy regimen including a fluoropyrimidine, a platinum compound and docetaxel (FLOT) demonstrated a better overall survival, the survival rate is still very low, and a massive effort is still required to improve clinical prognosis. High microsatellite instability (MSI-H) status in gastric cancer is a favorable prognostic factor but poor data are available on its predictive role for perioperative FLOT chemotherapy in resectable gastric cancer. Here, we presented the case of two patients with advanced MSI-H gastric cancer/EGJ adenocarcinoma who had no residual tumor following neoadjuvant FLOT chemotherapy maintaining a complete response for more than 30 months, suggesting MSI-H status to be a positive prognostic marker also in patients treated with a taxane-containing triplet in this setting. We also discuss the future perspectives including the opportunity to achieve excellent clinical outcomes with immune checkpoint inhibitor (ICI)-based regimens.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"85-88"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905674","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

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 : 2025-01-01 Epub 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":"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":" ","pages":"28-38"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","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

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 : 2024-11-01 Epub 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":" ","pages":"912-921"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462896/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0