Clinical cancer drugs最新文献

{"title":"Efficacy of gefitinib in patients with advanced non-small cell carcinoma of the lung harboring common, uncommon and complex EGFR mutations","authors":"W. Kwok, K. Chiang, J. Ho, T. Tam, M. Ip, D. Lam","doi":"10.2174/2212697x08666211029142257","DOIUrl":"https://doi.org/10.2174/2212697x08666211029142257","url":null,"abstract":"\u0000\u0000\u0000As the commonest EGFR-TKI being used in Hong Kong, gefitinib has shown to be efficacious and safe as first line treatment for L858R mutation and exon 19 deletion with less gastrointestinal and cutaneous adverse events than erlotinib and afatinib. However, the evidence for therapeutic efficacy for uncommon and complex EGFR mutations is lacking. Whether gefitinib is efficacious for uncommon and complex EGFR mutations worth studying.\u0000\u0000\u0000\u0000 To assess the therapeutic efficacy of gefitinib, as measured by progression-free survival and overall survival, among advanced stage lung cancer patients with common, uncommon and complex EGFR mutations.\u0000\u0000\u0000\u0000This is a retrospective cohort study that included 241 Chinese patients with advanced non-small cell carcinoma of lung harboring EGFR mutations and received gefitinib 250 mg daily as first-line treatment. The progression-free survival [PFS] and overall survival [OS] for patients with different EGFR mutations, namely exon 19 deletion, L858R mutation in exon 21, uncommon EGFR mutations and complex EGFR mutations were analyzed.\u0000\u0000\u0000\u0000\u0000\u0000Among the 241 patients, 118 [49%] had exon 19 deletion, 104 [43%] had L858R mutation in exon 21, 6 [2.5%] had uncommon EGFR mutations, 13 [5.4%] had complex EGFR mutations. The mean age was 69. 72% of the patients were female and with 81% being non-smoker. For patients with complex EGFR mutations, regardless of the presence of exon 19 deletion and L858R mutation as the component, have better PFS and OS than patients with single common EGFR mutations [Exon 19 deletion or L858R mutation]. Patients with uncommon EGFR mutations have inferior PFS and OS than those with common EGFR mutations.\u0000\u0000\u0000\u0000\u0000Gefitinib is a possible option for patients with complex EGFR mutations while it may not be the preferred treatment option in patients with single uncommon EGFR mutations.\u0000\u0000","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43961864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of ERN1 Signaling is Important for the Suppression of Tumor Growth","authors":"O. Minchenko, D. O. Tsymbal, Olena O. Khita, D. Minchenko","doi":"10.2174/2212697x08666211006100250","DOIUrl":"https://doi.org/10.2174/2212697x08666211006100250","url":null,"abstract":"\u0000\u0000 Endoplasmic reticulum to nucleus signaling 1 (ERN1) is a major signaling pathway of endoplasmic reticulum stress and is crucial for malignant tumor growth \u0000\u0000\u0000\u0000\u0000The article aims to discuss the recent progress in the discovery of endoplasmic reticulum stress targets and their involvement in tumor growth. \u0000\u0000\u0000\u0000\u0000Literature from the PubMed database related to the endoplasmic reticulum stress involvement in the tumor growth and chemoresistance was searched and reviewed.\u0000\u0000\u0000\u0000\u0000The endoplasmic reticulum stress plays an important part in malignant tumor growth and is involved in invasion and metastasis. Inhibition of protein kinase and endoribonuclease activities of the ERN1 signaling protein significantly reduces tumor growth through down-regulation of angiogenesis and cell proliferation but activates the invasion. ERN1 knockdown affects the expression of many genes associated with the regulation of apoptosis, cell proliferation and survival as well as reprograms the hypoxic regulation of most gene expressions. Simultaneously, inhibition of ERN1 endoribonuclease only has a stronger suppressive effect on tumor growth and decreases the invasiveness..\u0000\u0000\u0000\u0000\u0000Present review summarizes the recent advances in the inhibition of ERN1 signaling that regulates tumor growth. Further understanding of the regulatory mechanisms of genome reprogramming upon inhibition of ERN1 signaling may help to discover new possibilities for developing novel effective therapeutics.\u0000\u0000","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44705500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico Based Approach to Investigate Plant Lignans as inhibitor Candidates for Estrogen Receptor in Breast Cancer","authors":"F. Mohamadyar-Toupkanlou, Mina Esfandiari, Mahshid Sadat Kashef-Saberi, M. Kabiri, Zahra Bazi","doi":"10.2174/2212697x08666210923123117","DOIUrl":"https://doi.org/10.2174/2212697x08666210923123117","url":null,"abstract":"\u0000\u0000 In the last decades, growing evidence demonstrates interest in phytoestrogen intake to modulate targets in different types of cancer. Plant lignans have proven efficacious in blocking estrogen receptors of breast cancer cells. Among them, four phytoestrogen lignans: pinoresinol, matairesinol, lariciresinol, and secoisolariciresinol have been most studied. However, available studies have mostly dealt with anti-cancer effects of groups of lignans in certain foods or plants and the effects of specific lignans, especially from a molecular interaction viewpoint, have been rarely addressed in the literature. \u0000\u0000\u0000\u0000\u0000We aimed to in silico predict pharmacological properties, binding ability and binding strength of pinoresinol, matairesinol, lariciresinol and secoisolariciresinol as possible inhibitors of estrogen receptor alpha which is the most important biomarker in breast cancer.\u0000\u0000\u0000\u0000\u0000Firstly, we evaluated the pharmacological properties of four lignans using SwissADME. Then we investigated the ligand-receptor interactions of these molecules as positively appraised ligands for ER-positive breast cancer targeted therapy using docking method. We finally compared the inhibitory effect possibility of the lignans against endoxifen which is the active metabolite of tamoxifen.\u0000\u0000\u0000\u0000\u0000 The best binding affinity of endoxifen, matairesinol, pinoresinol, lariciresinol and secoisolariciresinol were respectively -9.2, -7.5, -6.7, -6.7, -5.8 kcal/mol. In the meantime, matairesinol showed the minimum binding energy than other studied lignans in addition to the most similar interactions to endoxifen with conserved domain residues of the active site pocket in Leu:391, Ala:350, Met:421, and Phe:404.\u0000\u0000\u0000\u0000\u0000Among the studied lignans, matairesinol showed the favorable pharmacokinetics and drug-likeliness properties, the least binding energy as well as the most common interactions in conserved residues of the active site pocket with estrogens. This makes it a molecule with low number of nonspecific interactions, better target selectivity, and hence fewer side effects. Thus, our results introduce matairesinol as a possibly effective anti-estrogen receptor inhibitor candidate.\u0000\u0000","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47446808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Anti-Angiogenic Effects of Elaeagnus angustifolia L. Extract in Vivo","authors":"Mohammad Sako, M. Zihlif, F. Afifi","doi":"10.2174/2212697x08666210906124143","DOIUrl":"https://doi.org/10.2174/2212697x08666210906124143","url":null,"abstract":"\u0000\u0000 Angiogenesis is the formation of new blood vessels from pre-existing ones. It occurs in both physiological and pathological conditions. \u0000\u0000\u0000\u0000We aimed to evaluate the antiangiogenic effect of Elaeagnus angustifolia L. water extract in vivo to determine any anti-proliferative effect of the extract on the A549 lung cancer cell line, and to investigate its effect on VEGF-A and FGF2 expression in the A549 cell line. \u0000\u0000\u0000\u0000Trypan blue exclusion test was implemented to establish any possible anti-proliferative effect of the extract. Then, Matrigel plug assay was performed on mice using the same cell line to test the antiangiogenic effect of the extract. Finally, A549 cells were treated with the extract at concentrations of 25, 12.5, and 6.25 µg/ml to investigate the changes in VEGF-A and FGF2 expression by RT-qPCR. \u0000\u0000\u0000\u0000E. angustifolia extract did not exhibit a significant anti-proliferative effect against A549 cells. The extract at concentrations of 12.5 and 6.25 µg/ml demonstrated an inhibitory effect against the growth of new blood vessels by 75.63 and 45.26%, respectively. The extract did not affect the expression of VEGF-A and FGF2 in A549 cells. \u0000\u0000\u0000\u0000Our findings show that water extract of E. angustifolia possesses potent antiangiogenic activity, while neither exhibiting significant anti-proliferative effect nor affecting VEGF-A or FGF2 expression in the A459 cell line, suggesting either sole direct antiangiogenic effect, or both direct and indirect effects with paracrine suppression of other genes.\u0000","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43505439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Antimalarial Drug Pyronaridine Inhibits Topoisomerase II in Breast Cancer Cells and Hinders Tumor Progression <i>In Vivo</i>.","authors":"Paulina J Villanueva,&nbsp;Denisse A Gutierrez,&nbsp;Lisett Contreras,&nbsp;Karla Parra,&nbsp;Aldo Segura-Cabrera,&nbsp;Armando Varela-Ramirez,&nbsp;Renato J Aguilera","doi":"10.2174/2212697x08666210219101023","DOIUrl":"https://doi.org/10.2174/2212697x08666210219101023","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most frequently diagnosed cancer in women worldwide. Pyronaridine (PND), an antimalarial drug, was shown to exert anticancer activity on seventeen different human cancer cells, seven from female breast tissue. Additionally, PND induced apoptosis <i>via</i> mitochondrial depolarization, alteration of cell cycle progression, and DNA intercalation. However, the molecular target of PND in cells was not elucidated.</p><p><strong>Objective: </strong>Here, we have further investigated PND's mode of action by using transcriptome analysis. Preclinical studies were also performed to determine whether PND could affect tumor progression in a human breast cancer xenograft in mice. Moreover, we assessed the combined efficacy of PND with well-known anticancer drugs.</p><p><strong>Methods: </strong>Transcriptome analyses of PND-treated cancer cells were performed. Topoisomerase II activity was evaluated by an <i>in vitro</i> assay. In addition, daily oral administration of PND was given to mice with human breast cancer xenografts. The differential nuclear staining assay measured <i>in-vitro</i> cell toxicity.</p><p><strong>Results: </strong>The transcriptome signatures suggested that PND might act as a topoisomerase II inhibitor. Thus, topoisomerase inhibition assays were performed, providing evidence that PND is a bona fide topoisomerase II inhibitor. Also, <i>in-vivo</i> studies suggest that PND hinders tumor progression. Besides, combination studies of PND with anticancer drugs cisplatin and gemcitabine revealed higher cytotoxicity against cancer cells than individual drug administration.</p><p><strong>Conclusion: </strong>The findings provide evidence that PND is a topoisomerase II inhibitor and can hinder cancer progression in an animal model, further demonstrating PND's favorable characteristics as a repurposed anticancer drug.</p>","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":"8 1","pages":"50-56"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849572/pdf/nihms-1750021.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39809862","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}

{"title":"COVID-19 Related Publications Focusing on Cancer: Systematic Review of a Delicate Balance","authors":"M. F. Naimi, Maira Khan, M. Mahler, U. Emmenegger","doi":"10.2174/2212697x07999201231200429","DOIUrl":"https://doi.org/10.2174/2212697x07999201231200429","url":null,"abstract":"\u0000\u0000The ongoing COVID-19 pandemic has forced oncologists to alter their daily practice, despite the lack of substantial evidence, in order to reduce the risk of transmission among patients with underlying malignant and other concurrent medical conditions.\u0000\u0000\u0000\u0000This systematic review compares the characteristics of oncology-focused COVID-19 manuscripts published from January 1st to April 30th, 2020, and from September 1st to September 30th, 2020, to identify the variation of publications between the start of the pandemic and our current state.\u0000\u0000\u0000\u0000The PubMed database was searched on two different occasions using the search string “Cancer OR Tumor” AND “COVID-19 OR SARS-CoV-2”. All manuscripts pertaining to COVID-19 and oncological topics were included in this review.\u0000\u0000\u0000\u0000The search from January 1st to April 30th, 2020 and from September 1st to September 30th, 2020, resulted in 299 and 249 articles pertaining to our objective, respectively. Comparing the earlier with later publication period, the proportion of articles containing original data increased from 22.4% to 44.2%, whereas the proportion of Editorials/Correspondences decreased from 43.5% to 20.5%. Cancer patient management guidelines accounted for the majority of publications during both periods (59.2% versus 43.4%, respectively).\u0000\u0000\u0000\u0000The study revealed a rapidly increasing number of COVID-19 and oncological-focused publications through-out the pandemic thus far. Given the unprecedented nature of the COVID-19 pandemic, future analyses are expected to reveal rapidly evolving publication patterns.\u0000","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42859317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial","authors":"G. Francia","doi":"10.2174/2212697x0702200923143757","DOIUrl":"https://doi.org/10.2174/2212697x0702200923143757","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48267550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meet Our Editorial Board Member","authors":"H. Newton","doi":"10.2174/2212697x0702200923121929","DOIUrl":"https://doi.org/10.2174/2212697x0702200923121929","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49639479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meet Our Editorial Board Member","authors":"D. Corina","doi":"10.2174/2212697x0701200204151957","DOIUrl":"https://doi.org/10.2174/2212697x0701200204151957","url":null,"abstract":"","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48573683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preface","authors":"G. Francia","doi":"10.2174/2212697x0701200204151859","DOIUrl":"https://doi.org/10.2174/2212697x0701200204151859","url":null,"abstract":"","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42152405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}