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Oncotarget
By Oncotarget PodcastScience
Oncotarget episodes
- Evaluation of Ruxolitinib, a Janus Kinase Inhibitor, in Multiple MyelomaBUFFALO, NY- February 7, 2024 – A new #research perspective was #published in Oncotarget's Volume 15 on February 5, 2024, entitled, “Preclinical and clinical evaluation of the Janus Kinase inhibitor ruxolitinib in multiple myeloma.”In this new paper, researchers Ashley Del Dosso, Elizabeth Tadevosyan, and James R. Berenson from ONCOtherapeutics, Berenson Cancer Center, and Institute for Myeloma and Bone Cancer Research discussed multiple myeloma (MM) — the most common primary malignancy of the bone marrow. No established curative treatment is currently available for patients diagnosed with MM.In recent years, new and more effective drugs have become available for the treatment of this B-cell malignancy. These new drugs have often been evaluated together and in combination with older agents. However, even these novel combinations eventually become ineffective; and, thus, novel therapeutic approaches are necessary to help overcome resistance to these treatments.Recently, the Janus Kinase (JAK) family of tyrosine kinases, specifically JAK1 and JAK2, has been shown to have a role in the pathogenesis of MM. Preclinical studies have demonstrated a role for JAK signaling in direct and indirect growth of MM and downregulation of anti-tumor immune responses in these patients. Also, inhibition of JAK proteins enhances the anti-MM effects of other drugs used to treat MM. These findings have been confirmed in clinical studies which have further demonstrated the safety and efficacy of JAK inhibition as a means to overcome resistance to currently available anti-MM therapies. Additional studies will provide further support for this promising new therapeutic approach for treating patients with MM.“The following sections of this article will be focused on studies of RUX [Ruxolitinib] in the preclinical [21–24] and clinical settings [18–20] focused on the treatment of relapsed/refractory (RR) MM.”DOI - https://doi.org/10.18632/oncotarget.28547Correspondence to - James R. Berenson - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28547Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, multiple myeloma, ruxolitinib, JAK/STAT, cytokine, clinical trialAbout OncotargetOncotarget (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, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia Contact180092209573 min
- Drug Discovery in Academia; Dumping in the Publication Landfill?BUFFALO, NY- February 5, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on January 24, 2024, entitled, “The fate of drug discovery in academia; dumping in the publication landfill?”In this new editorial, researchers Uzma Saqib, Isaac S. Demaree, Alexander G. Obukhov, Mirza S. Baig, Amiram Ariel, and Krishnan Hajela, from Devi Ahilya Vishwavidyalaya, Indore, discuss drug discovery—a tedious process that is time consuming in both divulging whether a molecule is efficacious and specific in hitting the target and also in confirming that the potential drug does not cause severe adverse effects. Many drug candidates fail crossing multiple checkpoints of this long journey; they lag in one or several aspects and never move beyond the research bench to contribute to public health. These setbacks make the process of drug discovery very time consuming, expensive, and tedious.“This viewpoint is focused on delineating how and why the multi-million [dollar] research efforts in the field of drug discovery often fail to reach its full potential.”There is no shortage of studies focusing on drug discovery. They are published on a daily basis describing the efforts encompassing conventional and/or modern drug discovery technology, including structure-based drug design (SBDD), virtual screening, high-throughput screening (HTS), Artificial Intelligence (AI), and cell-based screening approaches (Figure 1). However, many drug development strategies are rather fuzzy in their advancement.Thus, there is a large gap between drug “discovery” and “development.” This part could be attributed to the lack of synergy between Academia and Industry at multiple levels. A significant part of this failure results from the lack of streamlining of drug development process.“In the current perspective, we discussed why many therapeutic molecules never make it to clinical studies despite being proven efficacious pre-clinically. Additionally, we discussed the possible solutions to overcome this défaut of the drug development process.”DOI - https://doi.org/10.18632/oncotarget.28552Correspondence to - Krishnan Hajela - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28552Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, drug discovery and development, clinical trials, academia-industry collaboration, translational research, drug databaseAbout OncotargetOncotarget (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, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia Contact180092209573 min
- BCAS1 Defines a Heterogeneous Cell Population in Diffuse Glioma PatientsBUFFALO, NY- January 31, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on January 24, 2024, entitled, “BCAS1 defines a heterogeneous cell population in diffuse gliomas.”Oligodendrocyte precursor markers have become of great interest to identify new diagnostic and therapeutic targets for diffuse gliomas, since state-of-the-art studies point towards immature oligodendrocytes as a possible source of gliomagenesis. Brain enriched myelin associated protein 1 (BCAS1) is a novel marker of immature oligodendrocytes and was proposed to contribute to tumorigenesis in non-central nervous system tumors. However, the role of BCAS1 in diffuse glioma is still underexplored.In this new study, researchers Raquel Morales-Gallel, María José Ulloa-Navas, Patricia García-Tárraga, Ricardo Prat-Acín, Gaspar Reynés, Pedro Pérez-Borredá, Luis Rubio, Vivian Capilla-González, Jaime Ferrer-Lozano, and José Manuel García-Verdugo from the University of Valencia-CIBERNED, Mayo Clinic, Hospital Universitari i Politècnic La Fe, University of Pablo de Olavide, and University of Seville-CSIC analyzed the expression of BCAS1 in different tumor samples from patients with diffuse gliomas (17 oligodendrogliomas; 8 astrocytomas; 60 glioblastomas) and uncovered the molecular and ultrastructural features of BCAS1+ cells by immunostaining and electron microscopy.“Our results show that BCAS1+ cells exhibit stellate or spherical morphology with similar ultrastructural features.”Stellate and spherical cells were detected as isolated cells in all studied gliomas. Nevertheless, only stellate cells were found to be proliferative and formed tightly packed nodules with a highly proliferative rate in oligodendrogliomas. Their findings provide a comprehensive characterization of the BCAS1+ cell population within diffuse gliomas. The observed proliferative capacity and distribution of BCAS1+ stellate cells, particularly in oligodendrogliomas, highlight BCAS1 as an interesting marker, warranting further investigation into its role in tumor malignancy.“In conclusion, this insight will shed light on the establishment of BCAS1 as a clinically relevant molecule, serving not only as a diagnostic or prognostic marker but also as a novel therapeutic target for the development of cutting-edge treatments.”DOI - https://doi.org/10.18632/oncotarget.28553Correspondence to - José Manuel García-Verdugo - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28553Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, brain tumor, diffuse glioma, oligodendroglioma, glioblastoma, BCAS1About OncotargetOncotarget (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, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia Contact180092209574 min
- Gene Alterations in Thyroid Cancer Mediate Resistance to BRAF Inhibition & Anaplastic TransformationBUFFALO, NY- January 29, 2024 – A new #research perspective was #published in Oncotarget's Volume 15 on January 24, 2024, entitled, “Genetic alterations in thyroid cancer mediating both resistance to BRAF inhibition and anaplastic transformation.”In this new paper, researchers Mark Lee and Luc GT Morris from New York Presbyterian Hospital and Memorial Sloan Kettering Cancer Center discuss thyroid cancer. A subset of thyroid cancers present at advanced stage or with dedifferentiated histology and have limited response to standard therapy. Tumors harboring the BRAF V600E mutation may be treated with BRAF inhibitors; however, tumor response is often short-lived due to multiple compensatory resistance mechanisms.“One mode of resistance is the transition to an alternative cell state, which on rare occasions can correspond to tumor dedifferentiation.”DNA sequencing and RNA expression profiling show that thyroid tumors that dedifferentiate after BRAF inhibition are enriched in known genetic alterations that mediate resistance to BRAF blockade, and may also drive tumor dedifferentiation, including mutations in the PI3K/AKT/MTOR (PIK3CA, MTOR), MAP/ERK (MET, NF2, NRAS, RASA1), SWI/SNF chromatin remodeling complex (ARID2, PBRM1), and JAK/STAT pathways (JAK1). Given these findings, recent investigations have evaluated the efficacy of dual-target therapies; however, continued lack of long-term tumor control illustrates the complex and multifactorial nature of these compensatory mechanisms. Transition to an immune-suppressed state is another correlate of BRAF inhibitor resistance and tumor dedifferentiation, suggesting a possible role for concurrent targeted therapy with immunotherapy.“Investigations into combined targeted and immunotherapy are ongoing, but early results with checkpoint inhibitors, viral therapies, and CAR T-cells suggest enhanced anti-tumor immune activity with these combinations.”DOI - https://doi.org/10.18632/oncotarget.28544Correspondence to - Luc GT Morris - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28544Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, thyroid cancer, drug resistance, anaplastic transformation, BRAF inhibitors, PIK3CAAbout OncotargetOncotarget (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, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia Contact180092209573 min
- New Drug May Boost Effectiveness of Glioblastoma TreatmentGlioblastoma is a type of brain cancer that is very aggressive and difficult to treat. The current standard treatment involves surgery, radiation therapy, and chemotherapy with a drug called temozolomide (TMZ). However, many glioblastoma cells can resist the DNA-damaging effects of TMZ and radiation by activating a mechanism called the DNA damage response (DDR). This mechanism, while beneficial in normal cells, is detrimental to cancer therapy because it allows cancer cells to repair damage and continue to grow and divide. There is a need to counteract this mechanism in glioblastoma cancer cells.In a new study, researchers Mathew Lozinski, Nikola A. Bowden, Moira C. Graves, Michael Fay, Bryan W. Day, Brett W. Stringer, and Paul A. Tooney from University of Newcastle, Hunter Medical Research Institute, GenesisCare, QIMR Berghofer Medical Research Institute, and Griffith University found that a drug called gartisertib may overcome this resistance by inhibiting a key protein involved in the DDR, called ataxia-telangiectasia and Rad3-Related protein (ATR). On January 16, 2024, the researchers published their new research paper in Oncotarget’s Volume 15, entitled, “ATR inhibition using gartisertib enhances cell death and synergises with temozolomide and radiation in patient-derived glioblastoma cell lines.”Full blog - https://www.oncotarget.org/2024/01/25/new-drug-may-boost-effectiveness-of-glioblastoma-treatment/Paper DOI - https://doi.org/10.18632/oncotarget.28551Correspondence to - Paul A. Tooney - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28551Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, glioblastoma, DNA damage response, ataxia-telangiectasia and rad3-related protein, radiation therapy, temozolomideAbout OncotargetOncotarget (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, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media Contact180092209576 min
- Lazarus Effect in Patient Treated with Osimertinib for NSCLC with Leptomeningeal DiseaseBUFFALO, NY- January 24, 2024 – A new #case report was #published in Oncotarget's Volume 15 on January 16, 2024, entitled, “Lazarus effect in a patient initially empirically treated with osimertinib for EGFR L858R mutant non-small cell lung cancer with leptomeningeal disease: a case report.”Osimertinib has been shown to be effective for patients with non-small cell lung cancer (NSCLC) with activating EGFR mutations. These patients are also at risk for leptomeningeal disease (LMD). LMD is characterized by central nervous system metastases with spread to the cerebrospinal fluid or leptomeninges. In patients with NSCLC with EGFR activating mutations, there is an increased occurrence of LMD, which occurs in 9% of patients.In this new report, researchers Shreya Bhatia, Manuel G. Cortez, Spencer Lessans, and Wade T. Iams from Vanderbilt-Ingram Cancer Center present a patient of East Asian descent whose initial presentation included severe, progressive leptomeningeal carcinomatosis and a small lung mass, with limited tissue available for molecular testing. She responded to empiric, urgent initiation of osimertinib, repeat tissue sampling revealed an EGFR L858R mutation, and she has experienced durable disease improvement for 18 months on osimertinib monotherapy.“Our case demonstrates the nuances of decision-making in starting osimertinib in urgent clinical settings. Given our patient’s progressively worsening functional status and spread of disease to her CNS upon presentation, there was a need to begin treatment imminently. Time constraints, financial constraints, and lack of sufficient tissue for analysis ultimately led to the empiric use of osimertinib. Through the urgent initiation of appropriate anti-cancer therapy, she experienced both a life saving improvement in functional status and improvement in her LUL primary tumor one month into treatment.”DOI - https://doi.org/10.18632/oncotarget.28550Correspondence to - Wade T. Iams - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28550Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, EGFR mutation, leptomeningeal disease, non-small cell lung cancer, osimertinibAbout OncotargetOncotarget (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, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh?si=&nd=1&dlsi=c12c9dbac1be421dMedia Contact180092209573 min
- Published in Oncoscience: My Battle with Cancer. Part 1.BUFFALO, NY- January 22, 2024 – On January 3, 2024, Mikhail V. Blagosklonny M.D., Ph.D., from Roswell Park Comprehensive Cancer Center #published a new brief #report in Oncoscience (Volume 11), entitled, “My battle with cancer. Part 1.”“In January 2023, diagnosed with numerous metastases of lung cancer in my brain, I felt that I must accomplish a mission. If everything happens for a reason, my cancer, in particular, I must find out how metastatic cancer can be treated with curative intent. This is my mission now, and the reason I was ever born. In January 2023, I understood the meaning of life, of my life. I was born to write this article. In this article, I argue that monotherapy with targeted drugs, even when used in sequence, cannot cure metastatic cancer. However, preemptive combinations of targeted drugs may, in theory, cure incurable cancer. Also, I share insights on various topics, including rapamycin, an anti-aging drug that can delay but not prevent cancer, through my personal journey.”DOI - https://doi.org/10.18632/oncoscience.593Corresponding author - Mikhail V. Blagosklonny - [email protected], [email protected]Sign up for free Altmetric alerts about this article -https://oncoscience.altmetric.com/details/email_updates?id=10.18632%2Foncoscience.593Subscribe for free publication alerts from Oncoscience - https://www.oncoscience.us/subscribe/Keywords - cancer, lung cancer, brain metastases, capmatinib, resistance, METAbout OncoscienceOncoscience is a traditional, peer-reviewed, bio-medical oncology research journal with FREE publication for authors and open-access for readers.To learn more about Oncoscience, please visit https://www.oncoscience.us/ and connect with us:Facebook - https://www.facebook.com/OncoscienceX - https://twitter.com/OncoscienceJrnlInstagram - https://www.instagram.com/oncosciencejrnl/YouTube - https://www.youtube.com/@OncoscienceJournalLinkedIn - https://www.linkedin.com/company/oncoscience/Media Contact180092209572 min
- Bone Marrow Adipocytes Provide Early Sign of Progression from MGUS to Multiple MyelomaBUFFALO, NY- January 22, 2024 – A new #research perspective was #published in Oncotarget's Volume 15 on January 16, 2024, entitled, “Bone marrow adipocytes provide early sign for progression from MGUS to multiple myeloma.”Multiple Myeloma (MM) is the second most common hematological malignancy and is characterized by clonal expansion of malignant plasma cells in the bone marrow. In spite of recent advances in the field of MM, the disease has remained incurable. MM is preceded by a premalignant state known as monoclonal gammopathy of undetermined significance (MGUS), with a risk of progression to MM of 1% per year. Establishing a scalable approach that refines the identification of MGUS patients at high risk of progression to MM can transform the clinical management of the disease, improve the patient’s quality of life, and will have significant socioeconomic implications.In this new perspective, researchers Bilal M. El-Masri, Benedeta Leka, Fatima Mustapha, Michael Tveden Gundesen, Maja Hinge, Thomas Lund, Thomas L. Andersen, Marta Diaz-delCastillo, and Abbas Jafari from the Danish Spatial Imaging Consortium, University of Southern Denmark, University of Copenhagen, University of Aarhus, Odense University Hospital, and Lillebaelt Hospital provide evidence that changes in the bone marrow adipose tissue (BMAT) provide an early sign for progression from MGUS to MM.“We employed AI-assisted histological analysis of unstained bone marrow biopsies from MGUS subjects with or without progression to MM within 10 years (n = 24, n = 17 respectively).”Although the BMAT fraction was not different between the two groups, bone marrow adipocyte (BMAd) density was decreased in MGUS patients who developed MM, compared to non-progressing MGUS patients. Importantly, the distribution profile for BMAd size and roundness was significantly different between the two groups, indicating a shift toward increased BMAd size and roundness in MGUS patients who developed MM. These early changes in the BMAT could serve as valuable early indicators for the transition from MGUS to MM, potentially enabling timely interventions and personalized treatment strategies.“[...] the AI-based approach for histological characterization of unstained bone marrow biopsies is cost-effective and fast, rendering its clinical implementation feasible.”DOI - https://doi.org/10.18632/oncotarget.28548Correspondence to - Abbas Jafari - [email protected], Marta Diaz-delCastillo - [email protected], and Thomas L. Andersen - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28548Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, multiple myeloma, MGUS, bone marrow adipocyteAbout OncotargetOncotarget (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, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia Contact180092209574 min
- ATR Inhibition Using Gartisertib in Patient-derived Glioblastoma Cell LinesBUFFALO, NY- January 17, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on January 16, 2024, entitled, “ATR inhibition using gartisertib enhances cell death and synergises with temozolomide and radiation in patient-derived glioblastoma cell lines.”Glioblastoma cells can restrict the DNA-damaging effects of temozolomide (TMZ) and radiation therapy (RT) using the DNA damage response (DDR) mechanism which activates cell cycle arrest and DNA repair pathways. Ataxia-telangiectasia and Rad3-Related protein (ATR) plays a pivotal role in the recognition of DNA damage induced by chemotherapy and radiation causing downstream DDR activation.In this new study, researchers Mathew Lozinski, Nikola A. Bowden, Moira C. Graves, Michael Fay, Bryan W. Day, Brett W. Stringer, and Paul A. Tooney from University of Newcastle, Hunter Medical Research Institute, GenesisCare, QIMR Berghofer Medical Research Institute, and Griffith University investigated the activity of the ATR inhibitor gartisertib alone, and in combination with TMZ and/or RT, in multiple patient-derived glioblastoma cell lines.“Using a panel of 12 patient-derived glioblastoma cell lines, we investigated the chemo- and radio-sensitizing effect of gartisertib, a potent and selective inhibitor of ATR [26] that was explored in a phase 1 clinical trial for patients with advanced solid tumors (NCT02278250).”The team showed that gartisertib alone potently reduced the cell viability of glioblastoma cell lines, where sensitivity was associated with the frequency of DDR mutations and higher expression of the G2 cell cycle pathway. ATR inhibition significantly enhanced cell death in combination with TMZ and RT and was shown to have higher synergy than TMZ+RT treatment. MGMT promoter unmethylated and TMZ+RT resistant glioblastoma cells were also more sensitive to gartisertib. Analysis of gene expression from gartisertib treated glioblastoma cells identified the upregulation of innate immune-related pathways.“Overall, this study identifies ATR inhibition as a strategy to enhance the DNA-damaging ability of glioblastoma standard treatment, while providing preliminary evidence that ATR inhibition induces an innate immune gene signature that warrants further investigation.”DOI - https://doi.org/10.18632/oncotarget.28551Correspondence to - Paul A. Tooney - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28551Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, glioblastoma, DNA damage response, ataxia-telangiectasia and rad3-related protein, radiation therapy, temozolomideAbout OncotargetOncotarget (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, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media Contact180092209574 min
- Reductive Carboxylation of Glutamine as a Potential Target in AMLBUFFALO, NY- January 16, 2024 – A new #editorial paper was #published in Oncotarget's Volume 14 on December 1, 2023, entitled, “Reductive carboxylation of glutamine as a potential target in acute myeloid leukemia.”In this new editorial, researchers Alessia Roma, Lawrence D. Goodridge and Paul A. Spagnuolo from the University of Guelph discuss acute myeloid leukemia (AML) — an aggressive cancer of the blood and bone marrow defined by poor patient outcomes and sub-optimal therapeutics.Recent advancements in our understanding of AML biology bring optimism to improving patient outcomes for this devastating disease. For example, the discovery and validation of metabolic vulnerabilities that are distinct to AML open new strategies for novel drug development. In fact, since 2017, a third of newly approved AML therapeutics have targeted metabolic abnormalities. Thus, further identification and elucidation of metabolic vulnerabilities in AML could lead to novel therapies aimed at improving patient outcomes.“One approach is to weaken tumor cell survival mechanisms. In this regard, exploring reductive carboxylation as a possible drug target could provide new avenues for optimizing existing treatments aimed at improving AML patient outcomes.”DOI - https://doi.org/10.18632/oncotarget.28474Correspondence to - Paul A. Spagnuolo - [email protected]Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28474Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, acute myeloid leukemia, aml, reductive carboxylation, metabolism, mitochondria, complex IAbout OncotargetOncotarget (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, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media Contact180092209572 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.
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