239 episodes

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 Oncotarget Podcast

    • Science
    • 5.0 • 4 Ratings

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.

    Trending With Impact: Protein-Based Risk Model Predicts Esophageal Cancer Recurrence

    Trending With Impact: Protein-Based Risk Model Predicts Esophageal Cancer Recurrence

    Listen to a blog summary of a trending research paper published by Oncotarget, entitled, "Prediction of recurrence free survival for esophageal cancer patients using a protein signature based risk model."
    _________________________________________

    Esophageal cancer is the sixth most common cause of death from cancer worldwide. The two main types of esophageal cancer are adenocarcinoma and esophageal squamous cell carcinoma (ESCC). ESCC arises from the cells lining the esophagus, and it is most common in areas of the world where tobacco use and alcohol consumption are high.

    “Biomarkers to predict the risk of disease recurrence in Esophageal squamous cell carcinoma (ESCC) patients are urgently needed to improve treatment.”

    Researchers Raghibul Hasan, Gunjan Srivastava, Akram Alyass, Rinu Sharma, Anoop Saraya, Tushar K. Chattopadhyay, Siddartha DattaGupta, Paul G. Walfish, Shyam S. Chauhan, and Ranju Ralhan from All India Institute of Medical Sciences, Mount Sinai Hospital Toronto, McMaster University, Guru Gobind Singh Indraprastha University, and the University of Toronto conducted a new study on the protein expression-based risk model they developed to predict recurrence-free survival for ESCC patients. On September 14, 2022, their research paper was published in Oncotarget’s Volume 13, and entitled, “Prediction of recurrence free survival for esophageal cancer patients using a protein signature based risk model.”

    “Our study is important because: (i) it is based on changes in expression levels of the biomarker proteins in different subcellular compartments and is not limited to alterations in the overall protein expression levels; (ii) investigates the comprehensive clinical relevance of subcellular alterations in expression of multiple key components of Wnt pathway in the same ESCC patients’ cohort; (iii) correlates these findings with disease outcome and (iv) develops a Biomarker risk score for defining the risk of recurrence of ESCCs.”

    Full blog - https://www.oncotarget.org/2022/09/23/protein-based-risk-model-predicts-esophageal-cancer-recurrence/

    DOI - https://doi.org/10.18632/oncotarget.10656

    Correspondence to - Ranju Ralhan - rralhan@mtsinai.on.ca, Shyam S. Chauhan - s_s_chauhan@hotmail.com

    Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.10656

    Keywords - esophageal cancer, wnt proteins, disheveled, molecular markers, prognosis

    About Oncotarget

    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.

    To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

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    • 5 min
    Press Release: Targeting RCC w/Poly ADP-ribose Polymerase Inhibitors, Low-dose Alkylating Chemo

    Press Release: Targeting RCC w/Poly ADP-ribose Polymerase Inhibitors, Low-dose Alkylating Chemo

    BUFFALO, NY- September 20, 2022 – A new research paper was published in Oncotarget’s Volume 13 on September 14, 2022, entitled, “Targeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy.”

    Loss-of-function mutations in genes encoding the Krebs cycle enzymes Fumarate Hydratase (FH) and Succinate Dehydrogenase (SDH) induce accumulation of fumarate and succinate, respectively, and predispose patients to hereditary cancer syndromes including the development of aggressive renal cell carcinoma (RCC).

    Fumarate and succinate competitively inhibit αKG-dependent dioxygenases, including Lysine-specific demethylase 4A/B (KDM4A/B), leading to suppression of the homologous recombination (HR) DNA repair pathway.

    Researchers Daiki Ueno, Juan C. Vasquez, Amrita Sule, Jiayu Liang, Jinny van Doorn, Ranjini Sundaram, Sam Friedman, Randy Caliliw, Shinji Ohtake, Xun Bao, Jing Li, Huihui Ye, Karla Boyd, Rong Rong Huang, Jack Dodson, Paul Boutros, Ranjit S. Bindra, and Brian Shuch from Yale University School of Medicine, West China Hospital/School of Medicine, Wayne State University, and University of California, Los Angeles have developed new syngeneic Fh1- and Sdhb-deficient murine models of RCC, which demonstrate the expected accumulation of fumarate and succinate, alterations in the transcriptomic and methylation profile, and an increase in unresolved DNA double-strand breaks (DSBs).

    “In this study, we sought to examine the activity of combined TMZ and PARPi in Krebs-cycle-deficient renal cancer models. Fh1 and Sdhb are the murine counter part of human FH and SDHB, respectively.”

    The efficacy of poly ADP-ribose polymerase inhibitors (PARPis) and temozolomide (TMZ), alone and in combination, was evaluated both in vitro and in vivo. Combination treatment with PARPi and TMZ results in marked in vitro cytotoxicity in Fh1- and Sdhb-deficient cells. In vivo, treatment with standard dosing of the PARP inhibitor BGB-290 and low-dose TMZ significantly inhibits tumor growth without a significant increase in toxicity.

    These findings provide the basis for a novel therapeutic strategy exploiting HR deficiency in FH and SDH-deficient RCC with combined PARP inhibition and low-dose alkylating chemotherapy.

    “Using newly developed Fh1 and Sdhb deficient syngeneic mouse models, we demonstrate that oncometabolite-induced HR defects can be leveraged with PARPi treatment to enhance sensitivity to low-dose TMZ in Krebs-cycle-deficient renal cancer.”

    DOI: https://doi.org/10.18632/oncotarget.28273

    Correspondence to: Ranjit S. Bindra & Brian Shuch – Emails: Ranjit.Bindra@yale.edu & bshuch@mednet.ucla.edu

    Keywords: FH, SDHB, renal cell carcinoma, PARP inhibitor, temozolomide

    About Oncotarget:
    Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

    To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:

    Twitter – https://twitter.com/Oncotarget
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    For media inquiries, please contact: media@impactjournals.com.

    • 4 min
    Behind the Study: Inhibition of Resistant Triple-negative Breast Cancer Cells

    Behind the Study: Inhibition of Resistant Triple-negative Breast Cancer Cells

    Dr. Balraj Singh from the Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, describes a recent research paper he co-authored that was published by Oncotarget, entitled, “Inhibition of resistant triple-negative breast cancer cells with low-dose 6-mercaptopurine and 5-azacitidine.”

    DOI - https://doi.org/10.18632/oncotarget.27922

    Correspondence to - Anthony Lucci - alucci@mdanderson.org, and Balraj Singh - bsingh@mdanderson.org

    Video version - https://www.youtube.com/watch?v=TwIBNkUe1y4

    Abstract

    Highly adaptable breast cancer cells that can opportunistically switch between proliferation and quiescence are often responsible for disease relapse. We have developed a function-based selection strategy for such resistant cells, exemplified by SUM149-MA and FC-IBC02-MA triple-negative breast cancer cells. We have also reported that a lengthy treatment with low-dose 6-mercaptopurine, a clinically useful anti-inflammatory drug, inhibits such resistant cells. To more rigorously test the clinical suitability of 6-mercaptopurine, here we investigated effects of further lowering its dose and the possibility of overcoming resistance to single-drug treatment by combining the drug with another ribonucleoside analog 5-azacitidine. We found that that a lengthy treatment with 1 μM 5-azacitidine, without a significant effect on cell proliferation, sensitized cancer cells to the inhibitory effects of low-dose 6-mercaptopurine. Importantly, treatment for several weeks with low doses of 6-mercaptopurine and/or 5-azacitidine did not render cancer cells resistant to chemotherapeutic drugs doxorubicin or paclitaxel. In fact, the cells became more sensitive to chemotherapeutic drugs upon treatment with 6-mercaptopurine and/or 5-azacitidine. Our analyses of protein markers of epithelial-to-mesenchymal transition indicated that treatments with 6-mercaptopurine and/or 5-azacitidine do not significantly reverse this process in our model. Our results showed that safe drugs such as low-dose 6-mercaptopurine singly or combined with 5-azacitidine, which are suitable for use prior to disease relapse, have a potential of inhibiting highly resistant triple-negative breast cancer cells.

    Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27922

    Press release - https://www.oncotarget.com/news/pr/inhibition-of-resistant-triple-negative-breast-cancer-cells/

    Keywords - resistant TNBC, minimal residual disease, intratumor heterogeneity, breast cancer relapse, metastasis prevention

    About Oncotarget

    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.

    To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

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    18009220957

    • 9 min
    Press Release: An ABC Transporter as a Potential Target Against SHH-Medulloblastoma

    Press Release: An ABC Transporter as a Potential Target Against SHH-Medulloblastoma

    A new editorial paper was published in Oncotarget on September 8, 2022, by researchers Jingwen Zhu, Joseph N. Miller and John D. Schuetz from St. Jude Children’s Research Hospital in Memphis, Tennessee, entitled, “An ABC transporter as a potential target against SHH-Medulloblastoma: From Benchtop to Bedside.”

    Medulloblastoma (MB) is a common malignant pediatric brain tumor divided into four main subgroups (WNT, SHH, Group 3 and 4). The most prevalent MB in children 3 years is the Sonic Hedgehog (SHH) subtype, which arises from granule neuron progenitors with aberrant SHH signaling.

    While a standard treatment regimen includes tumor resection followed by a combination of craniospinal irradiation and chemotherapy, recommended treatment for patients 3 years consists of only chemotherapeutics as radiation therapy produces neuro-developmental side-effects. For SHH-MB, smoothened (SMO) inhibitors were initially seen as a promising therapy as SMO is central to SHH pathway activation. However, this approach yielded diminishing returns for young children due to: 1) SMO acquired therapy-induced drug-resistant mutations; 2) treatment with these inhibitors lead to irreversible developmental defects; and 3) gene alterations in SHH signaling downstream from SMO circumvent SMO inhibition. The discovery of novel modulators of the SHH pathway to advance SHH-MB treatment is greatly needed.

    “Thus, the identification of novel targetable regulators that function downstream of SMO is desirable to enhance SHH-MB therapy.”

    While the involvement of ATP-Binding Cassette (ABC) transporters in drug resistance is well studied, emerging studies have discovered their biological roles in tumorigenesis or cancer progression.

    Use of a data-driven systems biology approach led to the identification ABCC4 as a novel target of SHH-MB. Presumably this method could be expanded to uncover ABCC4’s role in other diseases with altered SHH signaling or other cancers in which high expression of ABCC4 is a hallmark of poor prognosis. Therefore, future studies should aim to obtain a better understanding of ABCC4’s biological roles in different cancers and to overcome therapeutic barriers in implementation of ABCC4 inhibitors.

    “These aims are fundamental in directing the development of ABCC4 inhibitors towards the ideal therapeutic strategy and providing a helpful guidance for clinical use to attain maximum efficacy.”

    DOI: https://doi.org/10.18632/oncotarget.28272

    Correspondence to: John D. Schuetz – Email: john.schuetz@stjude.org

    Keywords: transporter, chemotherapeutics

    About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

    To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:

    Twitter – https://twitter.com/Oncotarget
    Facebook – https://www.facebook.com/Oncotarget
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    For media inquiries, please contact: media@impactjournals.com.

    • 4 min
    Behind the Study: Targeting Lipid Metabolism in Treatment of Ovarian Cancer

    Behind the Study: Targeting Lipid Metabolism in Treatment of Ovarian Cancer

    Dr. Glenn Simmons Jr. from Cornell University College of Veterinary Medicine, and Dr. Stefani Thomas from University of Minnesota School of Medicine, detail a recent review they co-authored that was published by Oncotarget, entitled, “Targeting lipid metabolism in the treatment of ovarian cancer.”

    DOI - https://doi.org/10.18632/oncotarget.28241

    Correspondence to - Glenn E. Simmons Jr. - glenn.simmons@cornell.edu

    Video version - https://www.youtube.com/watch?v=RCvzLXZM1-A

    Abstract

    Cancer cells undergo alterations in lipid metabolism to support their high energy needs, tumorigenesis and evade an anti-tumor immune response. Alterations in fatty acid production are controlled by multiple enzymes, chiefly Acetyl CoA Carboxylase, ATP-Citrate Lyase, Fatty Acid Synthase, and Stearoyl CoA Desaturase 1. Ovarian cancer (OC) is a common gynecological malignancy with a high rate of aggressive carcinoma progression and drug resistance. The accumulation of unsaturated fatty acids in ovarian cancer supports cell growth, increased cancer cell migration, and worse patient outcomes. Ovarian cancer cells also expand their lipid stores via increased uptake of lipids using fatty acid translocases, fatty acid-binding proteins, and low-density lipoprotein receptors. Furthermore, increased lipogenesis and lipid uptake promote chemotherapy resistance and dampen the adaptive immune response needed to eliminate tumors. In this review, we discuss the role of lipid synthesis and metabolism in driving tumorigenesis and drug resistance in ovarian cancer conferring poor prognosis and outcomes in patients. We also cover some aspects of how lipids fuel ovarian cancer stem cells, and how these metabolic alterations in intracellular lipid content could potentially serve as biomarkers of ovarian cancer.

    Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28241

    Keywords - ovarian cancer, lipid metabolism, biomarkers, microenvironment, fatty acid

    About Oncotarget

    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.

    To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

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    18009220957

    • 8 min
    Press Release: Imaging With Polypeptide Fusion Protein Targets Bladder Cancer

    Press Release: Imaging With Polypeptide Fusion Protein Targets Bladder Cancer

    Listen to a press release about a new research paper published by Oncotarget, entitled, “Targeted elastin-like polypeptide fusion protein for near-infrared imaging of human and canine urothelial carcinoma.”

    _______________________________

    A new research paper was published in Oncotarget on September 6, 2022, entitled, “Targeted elastin-like polypeptide fusion protein for near-infrared imaging of human and canine urothelial carcinoma.”

    Bladder cancer (BC) is the 10th most common malignancy, affecting more than half a million people worldwide each year, and accounts for 4.6% of the total new cancer cases in the United States. With urothelial carcinoma (UC), the most common form of BC, the 5-year BC recurrence rate is nearly 78%, necessitating life-long surveillance, making it one of the costliest cancers to treat and manage. Cystoscopic visualization of bladder cancer is an essential method for initial bladder cancer detection and diagnosis, transurethral resection, and monitoring for recurrence.

    Researchers Aayush Aayush, Saloni Darji, Deepika Dhawan, Alexander Enstrom, Meaghan M. Broman, Muhammad T. Idrees, Hristos Kaimakliotis, Timothy Ratliff, Deborah Knapp, and David Thompson from Purdue University and Indiana University sought to develop a new intravesical imaging agent that is more specific and sensitive using a polypeptide based NIR (near-infrared) probe designed to detect cells bearing epidermal growth factor receptors (EGFR) that are overexpressed in 80% of urothelial carcinoma (UC) cases. The NIR imaging agent consisted of an elastin like polypeptide (ELP) fused with epidermal growth factor (EGF) and conjugated to Cy5.5 to give Cy5.5-N24-EGF as a NIR contrast agent. In addition to evaluation in human cells and tissues, the agent was tested in canine cell lines and tissue samples with naturally occurring invasive UC.

    “Dogs with naturally-occuring UC are an emerging option for a suitable large animal model of BC, where the cancer displays similar microscopic anatomy, histological appearance, biological behavior, heterogeneity, and molecular subtypes and markers to human invasive BC.”

    Full press release - https://www.oncotarget.com/news/pr/oncotarget-targeted-elastin-like-polypeptide-fusion-protein-for-near-infrared-imaging-of-human-and-canine-urothelial-carcinoma/

    DOI: https://doi.org/10.18632/oncotarget.28271

    Correspondence to: David Thompson – davethom@purdue.edu

    Keywords: bladder cancer, elastin-like polypeptide, NIR imaging, epidermal growth factor receptor (EGFR), translational studies

    About Oncotarget:

    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.

    To learn more about Oncotarget, visit Oncotarget.com and connect with us:

    Twitter – https://twitter.com/Oncotarget
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    For media inquiries, please contact: media@impactjournals.com

    • 4 min

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