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Oncotarget episodes
- Oncotarget: Biomarker Predicts Treatment Efficacy in Triple-Negative Breast CancerBiomarkers are any measurement in the body that can indicate disease, infection, or effects of the environment. These indicators are commonly used to reveal disease, but they can also be used to support personalized cancer therapy.“In recent years, there has been an increased focus on personalized cancer therapy. One important aspect is the identification of key biomarkers that support a given treatment plan.”Multiple biomarkers have been identified in breast cancers as helpful tools to guide targeted therapies, including the expression of HER2 and estrogen and progesterone receptors. In triple-negative breast cancer (TNBC), a number of distinct biomarkers have given rise to new targeted therapies, such as EGFR antibodies, AKT inhibitors, and PARP inhibitors.In a well-read paper from Immunomedics, Inc. (recently acquired by Gilead Sciences, Inc.), researchers analyzed sacituzumab govitecan (SG; Trodelvy™) in TNBC. The team authored a research paper that was published by Oncotarget in 2020, and entitled, “Predictive biomarkers for sacituzumab govitecan efficacy in Trop-2-expressing triple-negative breast cancer.” To date, this paper has scored an Altmetric Attention score of 48.“Here we examined the potential role of biomarkers in predicting the efficacy of SG.”Sacituzumab govitecan is an antibody-drug conjugate that targets human trophoblast cell-surface antigen-2 (Trop-2)ーwhich is a glycoprotein that is commonly overexpressed in many solid tumor types.“Trop-2 is a 46 KDa transmembrane glycoprotein that is overexpressed on many solid tumor types and is correlated with an overall poor prognosis in patients, making it an attractive target for therapy [7, 9].”The researchers examined a highly invasive and aggressive TNBC cell line (MDA-MB-231), which is not responsive to SG, and compared their findings to TNBC cell lines that are responsive to SG. Their goal was to determine how Trop-2 expression and the homologous recombination repair (HRR) pathway (through Rad51 expression) play roles in protecting the MDA-MB-231 cell line from SG mediated DNA damage.Trop-2 expression in transfected MDA-MB-231 and tumor xenografts were assessed, in vitro and in vivo Rad51 expression and DNA damagewere assessed via western blot, and statistical analysis was carried out for data from in vivo therapy studies.“Trop-2 expression levels as a positive, primary biomarker and HRR proficiency as a secondary, negative biomarker were assessed in vitro and in vivo.”Full blog: https://www.impactjournals.com/journals/blog/oncotarget/biomarker-predicts-treatment-efficacy-in-triple-negative-breast-cancer/Press release - https://www.oncotarget.com/news/pr/predictive-biomarkers-in-trop-2-expressing-triple-negative-breast-cancer/Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27766DOI - https://doi.org/10.18632/oncotarget.27766Full text - https://www.oncotarget.com/article/27766/text/Correspondence to - Thomas M. Cardillo - [email protected]Keywords - sacituzumab govitecan, Trop-2, biomarker, RAD51, triple-negative breast cancerAbout OncotargetOncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetYouTube - https://www.youtube.com/c/OncotargetYouTube/LinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnlsMedia Contact180092209576 min
- Oncotarget: LAPAS1 is required for S phase progression and cell proliferationOncotarget published "A novel E2F1-regulated lncRNA, LAPAS1, is required for S phase progression and cell proliferation" which reported that long non-coding RNAs are major regulators of many cellular processes, including cell cycle progression and cell proliferation.Inhibition of LAPAS1 expression increases the percentage of S phase cells, and its silencing in synchronized cells delays their progression through S phase.In agreement with its suggested role in cell cycle progression, prolonged inhibition of LAPAS1 attenuates proliferation of human cancer cells.Importantly, knockdown of SPNS2 rescues the effect of LAPAS1 silencing on cell cycle and cell proliferation.Summarily, they identify LAPAS1 as a novel E2F-regulated lncRNA that has a potential role in human cancer and regulates cell-cycle progression and cell proliferation, at least in part, via regulation of SPNS2.Dr. Doron Ginsberg from The Bar-Ilan University said, "The human genome expresses many thousands of long non-coding RNAs (lncRNAs), which are transcripts longer than 200 bases that lack a significant open reading frame."Increasing evidence indicates that lncRNAs are key regulators of important biological processes including cell cycle progression, cell proliferation and apoptosis.Specifically, some lncRNAs function in regulation of cell cycle progression via modulation of critical cell cycle players, such as the cyclins, CDKs, CDK inhibitors, pRB, and p53.Transcription factors that regulate mRNA transcription were shown to also regulate lncRNAs expression.Inhibition of LAPAS1 expression delays progression of cells through S phase and inhibits proliferation of human cancer cells.Thus, the authors identify LAPAS1 as a new E2F-regulated lncRNA that has a potential role in human cancer and regulates cell proliferation and cell-cycle progression, at least in part, via regulation of SPNS2.The Ginsberg Research Team concluded in their Oncotarget Research Output, "this study reports the identification of a novel lncRNA that affects cell cycle progression and cell proliferation and may affect cancer progression. Its initial characterization shows that it is transcriptionally regulated by E2F and it exerts its activity, at least in part, by regulating SPNS2."DOI - https://doi.org/10.18632/oncotarget.27962Full text - https://www.oncotarget.com/article/27962/text/Correspondence to - Doron Ginsberg - [email protected]Keywords - lncRNA, E2F, cell cycle, cell proliferationAbout OncotargetOncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnlsMedia Contact18009220957x105Copyright © 2021 Impact Journals, LLCImpact Journals is a registered trademark of Impact Journals, LLC3 min
- Oncotarget: Metal Compounds Induce DNA Instability In Cancer CellsOncotarget’s cover paper this week (Volume 12, Issue 15) is entitled, "Terpyridine platinum compounds induce telomere dysfunction and chromosome instability in cancer cells."About the Study:Researchers from the National Institutes of Health, University Paris-Saclay, Kazusa DNA Research Institute, and the University of Edinburgh used a dual-Human Artificial Chromosome (HAC) assay to analyze the genomic activity of six telomere-targeting platinum compounds.The dual-HAC assay was previously created by the researchers in this study to detect compounds that induce CIN through telomere dysfunction. This assay consists of two cell lines: one with telomeres, and one without. Disruption of the cell lines with telomeres denotes compound-induced CIN, and indicates potentially efficacious cancer therapeutics in vivo.“Recently we developed a dual-HAC-based assay allowing quantitative comparison of the efficiency and specificity of compounds to induce telomere dysfunction [36].”Pt-tpy, a terpyridine platinum compound, and five of its structurally modified derivatives were assayed to determine their efficacy in creating genomic instability in cancer cells via telomere disruption. The team evaluated the six compounds using two isogenic human fibrosarcoma cell lines, the dual-HAC assay, FISH analysis of EGFP-HACs, telomere fluorescent in situ hybridization (Telo-FISH), flow cytometry, calculation of the rate of spontaneous HAC loss and after compound treatment, cell viability testing for measuring HAC loss in response to drug treatment, cytokinesis-block micronucleus assay, immunofluorescence, and statistical analysis.“We found that treatment of cancer cells with either Pt-cpym, Pt-vpym, Pt-ttpy or Pt-tpy induces telomere dysfunction leading to high levels of chromosome instability.”Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28020DOI - https://doi.org/10.18632/oncotarget.28020Full text - https://www.oncotarget.com/article/28020/text/Correspondence to - Vladimir Larionov - [email protected] and Natalay Kouprina - [email protected]Keywords - chromosome instability, CIN, platinum-derived G4-quadruplexes, telomere dysfunction, human artificial chromosomeAbout OncotargetOncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetYouTube - https://www.youtube.com/c/OncotargetYouTube/LinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnlsMedia Contact180092209576 min
- Table of Contents: Oncotarget Volume 12, Issue #15Listen to summaries of the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 15.https://www.oncotarget.com/archive/v12/i15/Cover Paper - “Terpyridine platinum compounds induce telomere dysfunction and chromosome instability in cancer cells”https://doi.org/10.18632/oncotarget.28020Research Paper - “RNA expression differences in prostate tumors and tumor-adjacent stroma between Black and White Americans” https://doi.org/10.18632/oncotarget.28024Research Paper - “Next-generation multimodality of nutrigenomic cancer therapy: sulforaphane in combination with acetazolamide actively target bronchial carcinoid cancer in disabling the PI3K/Akt/mTOR survival pathway and inducing apoptosis”https://doi.org/10.18632/oncotarget.28011Research Paper - “The impact of neoadjuvant concurrent chemoradiation on exosomal markers (CD63 and CD9) expression and their prognostic significance in patients with rectal adenocarcinoma” https://doi.org/10.18632/oncotarget.28025Research Paper - “Identification of miR-203a, mir-10a, and miR-194 as predictors for risk of lymphovascular invasion in head and neck cancers” https://doi.org/10.18632/oncotarget.28022Research Paper - “JunD accentuates arecoline-induced disruption of tight junctions and promotes epithelial-to-mesenchymal transition by association with NEAT1 lncRNA” https://doi.org/10.18632/oncotarget.28026Research Paper - “Actionability evaluation of biliary tract cancer by genome transcriptome analysis and Asian cancer knowledgebase” https://doi.org/10.18632/oncotarget.28021Editorial - “Multidisciplinary clinics in prostate cancer” https://doi.org/10.18632/oncotarget.27984 (PDF Download)Research Perspective - “Developing next generation immunomodulatory drugs and their combinations in multiple myeloma”https://doi.org/10.18632/oncotarget.27973Keywords - chromosome instability, prostate cancer, sulforaphane, exosomes, head and neck cancer, miRNA, arecoline, biliary tract cancer, multiple myeloma, cancer, science, research, oncologyAbout OncotargetOncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetLinkedIn - https://www.linkedin.com/company/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/oncotargetyoutubePinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/OncotargetOncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnlsMedia Contact180092209579 min
- Oncotarget: Targeted Treatment for Recurrent Ovarian CancerOncotarget published this trending research paper on May 1, 2018, entitled, "Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau" by researchers from the Massachusetts General Hospital, Boston, MA; Siamab Therapeutics, Inc., Newton, MA; Harvard Medical School, Boston, MA.Abstract:Recurrent ovarian cancer (OvCa) is thought to result in part from the inability to eliminate rare quiescent cancer stem cells (CSCs) that survive cytotoxic chemotherapy and drive tumor resurgence. The Sialyl-Thomsen-nouveau antigen (STn) is a carbohydrate moiety present on protein markers of CSCs in pancreatic, colon, and gastric malignancies. We have demonstrated that human OvCa cell lines contain varying levels of cells that independently express either STn or the ovarian CSC marker CD133. Here we determine co-expression of STn and CD133 in a subset of human OvCa cell lines. Analyses of colony and sphere forming capacity and of response to standard-of-care cytotoxic therapy suggest a subset of OvCa STn+ cells display some CSC features. The effect of the anti-STn antibody-drug conjugates (ADCs) S3F-CL-MMAE and 2G12-2B2-CL-MMAE on OvCa cell viability in vitro and in vivo was also assessed. Treatment with S3F-CL-MMAE reduced the viability of two of three OvCa cell lines in vitro and exposure to either S3F-CL-MMAE or 2G12-2B2-CL-MMAE reduced OVCAR3-derived xenograft volume in vivo, depleting STn+ tumor cells. In summary, STn+ cells demonstrate some stem-like properties and specific therapeutic targeting of STn in ovarian tumors may be an effective clinical strategy to eliminate both STn+ CSC and STn+ non-CSC populations.Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.25289DOI - https://doi.org/10.18632/oncotarget.25289Full text - https://www.oncotarget.com/article/25289/text/Correspondence to - Bo R. Rueda - [email protected]Keywords - ovarian cancer, sialyl-Tn, antibody-drug conjugate, cancer stem cell, tumor-associated carbohydrate antigenAbout OncotargetOncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetYouTube - https://www.youtube.com/c/OncotargetYouTube/LinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnlsMedia Contact180092209576 min
- Oncotarget: Expanding Research With TrendMDOncotarget has started a new venture to expand our reach and connect with other relevant platforms using TrendMD. The TrendMD widget has been applied at the bottom of all research papers on Oncotarget.com to serve recommended content to our readers, and readers on thousands of other high-traffic websites and scholarly platforms. Recommended content is based on the content currently being viewed, content that has been viewed in the past, and content other similar readers are viewing.“[TrendMD’s] recommendation algorithms continuously optimize the placements of links to your content for the right audience while readers are actively looking for something interesting to discover.” —Source: TrendMD.comThis platform uses algorithms similar to those that Amazon uses to help bring fresh new relevant content to interested readers. The TrendMD widget recommends content both derived from Oncotarget.com and from other biomedical journals and articles publishing similar content. They also use collaborative filtering and track user behavior to learn how to suggest the right content for the right people.Oncotarget also uses TrendMD to help authors better circulate their research to targeted audiences around the world, cross-promote papers in adjacent fields, and increase paper citations. In a research study by Scientometrics, TrendMD was shown to outperform PubMed related citations by 272%. By joining this platform, Oncotarget publications are now incorporated into the TrendMD network—with 100 million total monthly users. Papers published by Oncotarget will now berecommended on hundreds of other leading peer-reviewed journals and scholarly websites.“TrendMD is the world’s leading discovery platform, delivering over 1 billion recommendations to over 100 million unique users each month on 4,500 websites from over 300 scholarly publishers.” —Source: TrendMD.comSince papers are recommended based on algorithms aiming to share specific content with readers who are most likely to be interested in the content, readership and engagement with TrendMD is very high. TrendMD statistics show that readers have the lowest bounce rate and view more content on TrendMD compared to Google AdWords, Google Scholar, Twitter, and PubPeer. Oncotarget is proud to offer this service for our authors and the scientific research community.Keywords - research, open access, publications, journals, papersAbout OncotargetOncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetYouTube - https://www.youtube.com/c/OncotargetYouTube/LinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnlsMedia Contact180092209574 min
- Oncotarget: Esomeprazole and Tumor ControlThis week's cover paper of Oncotarget (Volume 12, Issue 14) is entitled, "Esomeprazole enhances the effect of ionizing radiation to improve tumor control," by researchers from Baylor College of Medicine, University of Texas MD Anderson Cancer Center, and Texas Children’s Hospital.Abstract:The resistance of cancer cells to radiation-based treatment is a major clinical challenge confounding standard of care in cancer. This problem is particularly notable in many solid tumors where cancer cells are only partially responsive to radiation therapy. Combination of radiation with radiosensitizers is able to enhance tumor cell killing. However, currently available radiosensitizers are associated with significant normal tissue toxicity. Accordingly, there is an unmet need to develop safer and more effective radiosensitizers to improve tumor control. Here, we evaluated the radiosensitizing effect of the FDA-approved drug esomeprazole in normal and radioresistant human head and neck squamous cell carcinoma (HNSCC) cells in vitro, and in a mouse model of HNSCC. For the in vitro studies, we used cancer cell colony formation (clonogenicity) assay to compare cancer cell growth in the absence or presence of esomeprazole. To determine mechanism(s) of action, we assessed cell proliferation and profiled cell cycle regulatory proteins. In addition, we performed reverse phase protein array (RPPA) study to understand the global effect of esomeprazole on over 200 cancer-related proteins. For the in vivo study, we engrafted HNSCC in a mouse model and compared tumor growth in animals treated with radiation, esomeprazole, and combination of radiation with esomeprazole. We found that esomeprazole inhibits tumor growth and dose-dependently enhances the cell killing effect of ionizing radiation in wildtype and p53-mutant radioresistant cancer cells. Mechanistic studies demonstrate that esomeprazole arrests cancer cells in the G1 phase of the cell cycle through upregulation of p21 protein and inhibition of cyclin-dependent kinases (Cdks) type 1 (Cdk1) and type 2 (Cdk2). In vivo data showed greater tumor control in animals treated with combination of radiation and esomeprazole compared to either treatment alone, and that this was associated with inhibition of cell proliferation in vivo. In addition, combination of esomeprazole with radiation significantly impaired repair following radiation-induced DNA damage. Our studies indicate that esomeprazole sensitizes cancer cells to ionizing radiation, and is associated with upregulation of p21 to arrest cells in the G1 phase of the cell cycle. Our findings have significant therapeutic implications for the repurposing of esomeprazole as a radiosensitizer in HNSCC and other solid tumors.Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28008DOI - https://doi.org/10.18632/oncotarget.28008Full text - https://www.oncotarget.com/article/28008/text/Correspondence to - Yohannes T. Ghebre - [email protected]Keywords - esomeprazole, proton pump inhibitors, ionizing radiation, radiosensitization, tumor controlAbout OncotargetOncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetYouTube - https://www.youtube.com/c/OncotargetYouTube/LinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnlsMedia Contact180092209574 min
- Table of Contents: Oncotarget Volume 12, Issue #14Listen to short summaries of the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 14.https://www.oncotarget.com/archive/v12/i14/Cover Paper - “Esomeprazole enhances the effect of ionizing radiation to improve tumor control” https://doi.org/10.18632/oncotarget.28008Research Paper - “Mebendazole disrupts stromal desmoplasia and tumorigenesis in two models of pancreatic cancer”https://doi.org/10.18632/oncotarget.28014Research Paper - “MRI texture features from tumor core and margin in the prediction of response to neoadjuvant chemotherapy in patients with locally advanced breast cancer” https://doi.org/10.18632/oncotarget.28002Research Paper - “The use of a uPAR-targeted probe for photothermal cancer therapy prolongs survival in a xenograft mouse model of glioblastoma”https://doi.org/10.18632/oncotarget.28013Research Paper - “Eltrombopag and its iron chelating properties in pediatric acute myeloid leukemia” https://doi.org/10.18632/oncotarget.28000Research Paper - “Prokineticin-1 induces normal lymphangiogenic activity and is involved in lymphangiogenesis and lymph node metastasis in colorectal cancer” https://doi.org/10.18632/oncotarget.28016Research Paper - “Appropriate body mass index cutoffs for type 2 diabetes in Xinjiang population: defining the influence of liver aminotransferase” https://doi.org/10.18632/oncotarget.28009Review - “Multifaceted effect of chlorpromazine in cancer: implications for cancer treatment” https://doi.org/10.18632/oncotarget.28010Research Perspective - “Targeting cancer associated fibroblasts to enhance immunotherapy: emerging strategies and future perspectives” https://doi.org/10.18632/oncotarget.27936Research Perspective - “A Dynamic Energy Budget (DEB) based modeling framework to describe tumor-in-host growth inhibition and cachexia onset during anticancer treatment in in vivo xenograft studies” https://doi.org/10.18632/oncotarget.27960Keywords - mebendazole, pancreatic cancer, esomeprazole, tumor control, MRI, breast cancer, eltrombopag, colorectal cancer, AML, type 2 diabetes, chlorpromazine, immunotherapy, tumors, cancer, science, research, oncologyAbout OncotargetOncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetLinkedIn - https://www.linkedin.com/company/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/oncotargetyoutubePinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/OncotargetOncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnlsMedia Contact180092209579 min
- Oncotarget: Breast cancer cells to ONC201 from anti-proliferative to apoptoticOncotarget published "TRAIL receptor agonists convert the response of breast cancer cells to ONC201 from anti-proliferative to apoptotic" which reported normal fibroblasts do not undergo apoptosis following rhTRAIL plus ONC201. In vivo, MDA-MB-361 tumor growth rate is significantly reduced following treatment with a combination of ONC201 and rhTRAIL as compared to control tumors.Natural killer cells which use TRAIL to kill DR5-expressing cancer cells, exhibit greater cytotoxicity against ONC201-treated breast cancer cells compared to controls.rhTRAIL also converts the response of cells from other tumor types to ONC201 from anti-proliferative to apoptotic.A monoclonal DR5-agonistic antibody converts the response of non-TNBC cells to ONC201 from anti-proliferative to apoptotic.These Oncotarget findings describe a novel therapeutic strategy that potently converts the response of a cancer cell to ONC201 from anti-proliferative to apoptotic.Dr. Wafik S. El-Deiry Founding Editorial Board Member of Oncotarget said, "Breast cancer is the most commonly diagnosed cancer and is the number three cause of cancer-related death in United States women."The potential of TRAIL to kill cancerous cells while leaving normal cells unharmed led to the development and clinical testing of TRAIL-based therapies such as recombinant human TRAIL and death receptor agonistic antibodies.ONC201 potently induced cell death through the extrinsic pathway in cancer cells from a variety of tumor types.The compound is unique in that it is a dual activator of the TRAIL pathway, able not only to upregulate pro-death ligand TRAIL, but also its receptor DR5. Early studies of the mechanism of action of ONC201 showed that the compound inhibited pro-survival kinases Akt and ERK, leading to the dephosphorylation and activation of transcription factor FOXO3a.Previous work has shown that ONC201 is a potent dual inducer of the TRAIL pathway at the level of both the ligand and the receptor, and that breast cancers show decreased sensitivity to TRAIL .The authors hypothesized that profiling the effects of the compound on the TRAIL pathway in breast cancer and identifying blocks in signal transduction would allow us to identify therapeutic strategies with the potential to induce apoptosis and that could potentially translate to tumor regressions in patients who do not respond to treatment with ONC201 alone.The El-Deiry Research Team concluded in their Oncotarget Research Output that this team's previous data showed that in breast cancer, the anti-proliferative effects of ONC201 are more common than the apoptotic effects.While the apoptotic effects of ONC201 led to in vivo efficacy of the compound, the anti-proliferative effects did not.In the present study, they investigated mechanisms as well as strategies to convert the response of breast cancer cells to ONC201 from anti-proliferative to pro-apoptotic.TRAIL receptor agonists such as rhTRAIL or a DR5-agonistic antibody convert the response of these cells to ONC201 from anti-proliferative to apoptotic.These findings may have clinical relevance as ONC201 is currently being tested in patients with breast cancer, and the authors believe that this newly identified combinatorial strategy has the potential to induce tumor regressions in patients with limited response to ONC201 monotherapy.DOI - https://doi.org/10.18632/oncotarget.27773Full text - https://www.oncotarget.com/article/27773/text/Correspondence to - Wafik S. El-Deiry - [email protected]Keywords - ONC201, TRAIL, breast cancer, death receptors, apoptosis36 min
- Oncotarget: ONC201 Induces Apoptosis in Breast CancerOncotarget published this trending research paper on October 20, 2020, entitled, "TRAIL receptor agonists convert the response of breast cancer cells to ONC201 from anti-proliferative to apoptotic" by researchers from Temple University, Philadelphia, PA; Fox Chase Cancer Center, Philadelphia, PA; Brown University, Providence, RI; Brown University and the Lifespan Health System, Providence, RI.Abstract:ONC201 was initially identified as an inducer of cell death through the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway. The compound is currently being tested in patients with hematological malignancies and solid tumors, including those of the breast. We investigated strategies to convert the response of breast cancers to ONC201 from anti-proliferative to apoptotic. ONC201 treatment upregulates TRAIL and primes TRAIL-resistant non-triple negative breast cancer (TNBC) cells to undergo cell death through the extrinsic pathway. Remarkably, the addition of exogenous recombinant human TRAIL (rhTRAIL) converts the response of TRAIL-resistant non-TNBC cells to ONC201 from anti-proliferative to apoptotic in a death receptor 5 (DR5)-dependent manner in vitro. Importantly, normal fibroblasts do not undergo apoptosis following rhTRAIL plus ONC201. In vivo, MDA-MB-361 tumor growth rate is significantly reduced following treatment with a combination of ONC201 and rhTRAIL as compared to control tumors. Natural killer (NK) cells which use TRAIL to kill DR5-expressing cancer cells, exhibit greater cytotoxicity against ONC201-treated breast cancer cells compared to controls. rhTRAIL also converts the response of cells from other tumor types to ONC201 from anti-proliferative to apoptotic. A monoclonal DR5-agonistic antibody converts the response of non-TNBC cells to ONC201 from anti-proliferative to apoptotic. Our findings describe a novel therapeutic strategy that potently converts the response of a cancer cell to ONC201 from anti-proliferative to apoptotic. This approach may be clinically relevant and has potential to induce tumor regression of patient tumors with relative resistance to ONC201 monotherapy.Press release - https://www.oncotarget.com/news/pr/breast-cancer-cells-to-onc201-from-anti-proliferative-to-apoptotic/Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27773DOI - https://doi.org/10.18632/oncotarget.27773Full text - https://www.oncotarget.com/article/27773/text/Correspondence to - Wafik S. El-Deiry - [email protected]Keywords - ONC201, TRAIL, breast cancer, death receptors, apoptosisAbout OncotargetOncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetYouTube - https://www.youtube.com/c/OncotargetYouTube/LinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnlsMedia Contact180092209577 min
About Oncotarget
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Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.
Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.
Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/