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Oncotarget
By Oncotarget PodcastScience
Oncotarget episodes
- Genomic and Neoantigen Evolution in Head and Neck Squamous Cell CarcinomaOncotarget published "Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma" which reported that prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution.These authors characterized genomic and neoantigen changes between 23 paired primary and recurrent head and neck squamous cell carcinoma (HNSCC) tumors.Within these tumors, they identified 6 genes which have predicted neoantigens in 4 or more patients.Within HNSCC tumors examined in this Oncotarget research paper, there are neoantigens in shared genes by a subset of patients.The presence of neoantigens in these shared genes may promote an anti-tumor immune response which controls tumor progression.Dr. Brian A. Van Tine from The Washington University in St. Louis, The St. Louis Children's Hospital as well as The Siteman Cancer Center said, "Head and neck cancer are a group of heterogeneous tumors with an estimated 644,000 new cases per year worldwide."The infiltration of immune cells, including T cells, into tumors is associated with improved outcomes and longer survival in HNSCC.The infiltrating T cells release granules containing perforin and granzyme A and B which directly kill tumor cells or release other cytokines and chemokines that promote the anti-tumor immune response and alter the tumor microenvironment.For example, infiltrating T cells release interferon gamma which increases expression of PD-L1 and CTLA-4, which may increase the efficacy of immune checkpoint therapy.Multiple studies have characterized changes in mutation burden in HNSCC, when comparing primary and metastatic tumors, no studies have characterized the shifting neoantigen burden between primary and metastatic tumors within HNSCC.In this Oncotarget study, the authors characterized the mutational and neoantigen burden between primary and first recurrence tumors in 23 patients with HNSCC.The Van Tine Research Team concluded in their Oncotarget Research Output that there is a shifting neoantigen burden as there are unique neoantigens in primary tumors and different unique neoantigens in the recurrent/metastatic tumors.The patients which have these neoantigens in shared genes are patients which have higher total numbers of neoantigens.What is clear is that patients with neoantigens in these shared genes also tend to have increased duration of survival with disease.The increase in neoantigens and duration of survival with disease tends to be associated with increased CD3 CD8 density in the tumor and CD8A expression.This suggests that patients with these shared neoantigens are associated with increased CD8 T cell infiltration and increased cytotoxic activity, which extends the patient's life.DOI - https://doi.org/10.18632/oncotarget.27907Full text - https://www.oncotarget.com/article/27907/text/Correspondence to - Brian A. Van Tine - [email protected]Keywords - head and neck squamous cell carcinoma, neoantigens, mutational evolution, tumor relapse, immune cell infiltrationAbout OncotargetOncotarget is a 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 Contact18009220957x10510 min
- Lung Cancer Antigen Expression Characterized by Molecular SubtypeLung cancer continues to be the leading cause of cancer deaths world-wide. Variations in the stage of diagnosis, subtypes and types of mutated genes provide a challenge for researchers who are developing targeted treatments to help rid patients of lung cancer. To this end, many researchers are interested in employing cancer-testis antigens (CTAs), which are minimally expressed in normal tissues, but strongly expressed in solid tumors. Therefore, CTAs are appealing therapeutic targets. The Kita-Kyushu lung cancer antigen-1 (also known as KK-LC-1; CT 83; CXORF61) is a CTA that is expressed in 82% of gastric tumors, 53% of breast cancers (higher in triple-negative breast cancer) and in about 33% of lung cancers.“In lung cancer, surgical series have shown KK-LC-1 to be expressed in about one-third of lung cancer tumors [1, 3–5].”Researchers—from the University of Southern California, Caris Life Sciences, Fox Chase Center, Georgetown Lombardi Comprehensive Cancer Center, The Warren Alpert Medical School of Brown University, Wayne State University School of Medicine, The Barbara Karmanos Cancer Institute, St. Marianna University, and the University of Utah—conducted a recent study to determine exactly which molecular subtypes of KK-LC-1 expressing lung cancer would be most responsive to a clinical trial involving the treatment of cancer with activated T lymphocytes from the body, or T cell receptor therapy (TCR-T), targeting KK-LC-1. Their research paper was published as cover of Oncotarget’s Volume 12, Issue 25, and entitled, “Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas”.Full blog - https://www.oncotarget.org/2021/12/08/lung-cancer-antigen-expression-characterized-by-molecular-subtype/Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28132DOI - https://doi.org/10.18632/oncotarget.28132Full text - https://www.oncotarget.com/article/28132/text/Correspondence to - Jorge J. Nieva - [email protected]Keywords - lung cancer, tumor microenvironment, diagnostic biomarkers, biomarkers for immunotherapy, cancer testis 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/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - 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 Contact180092209578 min
- Table of Contents: Volume 12, Issue #25View the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 25.https://www.oncotarget.com/archive/v12/i25/Research Paper (Cover) - “Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas”https://doi.org/10.18632/oncotarget.28132Research Paper - “Radiomics in predicting recurrence for patients with locally advanced breast cancer using quantitative ultrasound”https://doi.org/10.18632/oncotarget.28139Research Paper - “Beneficial effect of KYP-2047, a propyl-oligopeptidase inhibitor, on oral squamous cell carcinoma”https://doi.org/10.18632/oncotarget.28147Editorial - “Delivering albumin-bound paclitaxel across the blood-brain barrier for gliomas”https://doi.org/10.18632/oncotarget.28018 (PDF Download)Research Perspective - “Cell fusion as a link between the SARS-CoV-2 spike protein, COVID-19 complications, and vaccine side effects”https://doi.org/10.18632/oncotarget.28088Keywords - lung cancer, tumor microenvironment, radiomics, breast cancer, oral squamous cell carcinoma (OSCC), glioblastoma, cell fusion, 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 Contact180092209575 min
- Zebrafish B Cell Acute Lymphoblastic Leukemia: New Findings in Old ModelOncotarget Volume 11 Issue 15 reported that several zebrafish T-ALL models have been reported, but until recently, robust D. rerio B-ALL models were not described.Here, the Research Team has shown new B-ALL findings in one of these models, fish expressing transgenic human MYC.They describe B-ALL incidence in a large cohort of hMYC fish, and show B-ALL in two new lines where T-ALL does not interfere with B-ALL detection.Dr. J. Kimble Frazer from the Department of Cell Biology and the Department of Pediatrics, Section of Pediatric Hematology-Oncology, as well as the Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA said, "Acute lymphoblastic leukemia (ALL) and the related malignancy lymphoblastic lymphoma (LBL) dominate pediatric oncology, together representing over one third of all childhood cancer."For T-ALL in particular, zebrafish models have been highly informative, advancing our understanding of T-ALL genetics, pro- and anti-oncogenic interactions between different genes and pathways, tumor heterogeneity, leukemia stem cells, and in screens for new therapeutics.However, despite the fact that zebrafish T-ALL models had proven to be fertile grounds for study, B-ALL modeling in D. rerio had not been fruitful, with only one low penetrance and long latency line reported.This was curious because zebrafish recombination activating gene 2 promoters active in both immature T and B cells was used to regulate most of these transgenic oncoproteins in the various T-ALL lines, yet D. rerio B-ALL had not been reported in them.In 2018, the zebrafish ALL field advanced suddenly with reports of B-ALL in two closely-related transgenic lines where T-ALL was already known to occur.Here, the authors present new results in the hMYC model, including B- and T-ALL latency and penetrance data in a cohort of over 600 animals, in vivo glucocorticoid and radiation treatment of B-ALL, and expression profiles from single B- and T-ALL cells.The Frazer Research Team concluded in their Oncotarget Research Perspective, "We postulate these and other differences may explain the apparently disparate oncogenic mechanisms employed by hMYC and mMyc in the B lymphoblasts of these closely-related lines. Pathway analysis of differentially-regulated genes predicted differing activation of several biologic pathways (e.g., cell differentiation, immune system process, lymphocyte activation, RNA binding, etc.; Figure 6B panels and Supplementary Table 4). These markedly different pathway signatures further demonstrate that human and murine MYC are far from synonymous in terms of their oncogenic effects upon zebrafish B lymphoblasts."Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27555DOI - https://doi.org/10.18632/oncotarget.27555Full text - https://www.oncotarget.com/article/27555/text/Correspondence to - J. Kimble Frazer - [email protected]Keywords - acute lymphoblastic leukemia, ALL, zebrafish, lymphocyte, MYCAbout OncotargetOncotarget is a 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/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - 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 Contact1800922095726 min
- CrkL Required for Donor T Cell Migration to GvHD Target OrgansOncotarget published "CrkL is required for donor T cell migration to GvHD target organs" which reported that the success of cancer therapies based on allogeneic hematopoietic stem cell transplant relies on the ability to separate graft-versus-host disease from graft-versus-tumor responses.In vitro, CrkL-deficient T cells fail to polymerize actin in response to the integrin ligand ICAM-1, resulting in defective migration. In line with this, these authors found that although CrkL-deficient T cells could clear hematopoietic tumors, they failed to clear the same tumor growing subcutaneously, highlighting the role of CrkL in controlling T cell migration into peripheral tissues.Dr. Mobin Karimi from The SUNY Upstate Medical University said, "T cell migration out of the vasculature into peripheral tissue is a key control point in the inflammatory response."Although trafficking to tissues is required for protective immunity, uncontrolled T cell infiltration into tissue can result in exacerbated inflammation and tissue damage. T cell recruitment is highly regulated by the local endothelial cells which, in response to pro-inflammatory cues, up-regulate molecules such as chemokines and adhesion receptors. These molecules promote T cell adhesion to the endothelial monolayer, and guide migration through the monolayer into the tissue.Activated T cells lacking Crk proteins fail to polymerize actin downstream of LFA-1, and migrate slower and less directionally than their WT counterparts. Importantly, these mutant T cells also have defects in crossing endothelial monolayers in vitro, and they fail to traffic to sites of inflammation in vivo.Additionally, using a clinically relevant mouse model of graft-versus-host disease/graft-versus-leukemia, these authors showed that T cells lacking Crk proteins can efficiently clear tumor cells but cause little-to-no GvHD pathology. The Crk proteins are widely expressed across tissues and have many biological functions, all of which stem from their role as adaptor proteins that coordinate signaling complexes downstream of cell surface receptors.Crk proteins are particularly important for adhesion and migration. They have been shown to localize to adhesion sites and regulate the stability of these structures in non-hematopoietic cells, and alterations in their expression are associated with invasive potential in several tumors.The Karimi Research Team concluded in their Oncotarget Research Output, "Going forward, it will be interesting to identify CrkL binding partners and other signaling molecules needed for integrin-dependent actin responses and passage into inflamed tissues. Targeting these molecules could be used to more finely control T cell trafficking in the treatment of inflammatory diseases and for the design of next-generation adoptive T cell therapies."Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27509DOI - https://doi.org/10.18632/oncotarget.27509Full text - https://www.oncotarget.com/article/27509/text/Correspondence to - Mobin Karimi - [email protected]Keywords - graft-versus-host disease, CrkL, T cell, migration, inflammationAbout OncotargetOncotarget is a 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 @ImpactJrnlsCopyright © 2021 Impact Journals, LLCImpact Journals is a registered trademark of Impact Journals, LLC9 min
- Exploratory Study of Metformin and Rapamycin as Maintenance TherapyVolume 11, Number 21 of Oncotarget reported that eligible patients with stable or responding mPDA after 6 months on chemotherapy were randomized 1:1 to metformin alone or with rapamycin, stratified by prior treatment with FOLFIRINOX. Metformin +/ rapamycin maintenance for mPDA was well-tolerated and several patients achieved stable disease associated with exceptionally long survival.Dr. Dung T. Le from The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21287 said, "Pancreatic ductal adenocarcinoma (PDA) is aggressive cancer with high mortality at all stages and limited treatment options in the advanced setting."Metformin is an antidiabetic drug in the biguanide class of agents which inhibits mTOR complex 1 primarily through AMP-kinase activation.A synergistic effect of the combination of metformin with rapamycin was suggested by preclinical studies demonstrating enhanced inhibition of mTOR in a pancreatic cancer cell line and better growth inhibition of pancreatic cancer cells in a xenograft tumor model with the combination than either agent alone.Based on this, they conducted an exploratory study of metformin with or without rapamycin in patients with mPDA in the maintenance setting.The Le Research Team concluded in their Oncotarget Research Article, "the administration of metformin with or without rapamycin in patients with mPDA who achieve a response to chemotherapy is well-tolerated and was associated with better than expected overall survival in this study. Additional studies are needed to prospectively evaluate the role of these agents compared to a maintenance chemotherapy or observation only approach."Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27586DOI - https://doi.org/10.18632/oncotarget.27586Full text - https://www.oncotarget.com/article/27586/text/Correspondence to - Dung T. Le - [email protected]Keywords - pancreatic cancer, mTOR inhibition, maintenance therapy, metforminAbout OncotargetOncotarget is a 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/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - 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 Contact18009220957Copyright © 2021 Impact Journals, LLCImpact Journals is a registered trademark of Impact Journals, LLC7 min
- Testimonial: Dr. Jennifer Sheng from Johns Hopkins Cancer CenterOncotarget published "Innovating and expanding weight loss strategies for breast cancer survivors" which reported that overweight and obesity are prevalent in over two thirds of the general population in the United States and are associated with an increased risk of malignancies, including breast cancer.This weight gain may increase risk of recurrence by 40–50%, and breast cancer-related mortality by 53–60% . Obesity at and following a breast cancer diagnosis is associated with poor quality of life and increased risk of adverse treatment effects.Dr. Jennifer Y. Sheng from The Johns Hopkins Sidney Kimmel Comprehensive Cancer Center said, "...survivorship guidelines recommend that weight loss should be a priority for overweight/obese survivors."Numerous clinical trials have tested behavioral strategies for weight loss in survivors of early stage breast cancer, including modifications in diet, remote or group interventions. These authors evaluated several outcomes including: whether a 12-month remotely delivered behavioral weight loss intervention allows a greater proportion of breast cancer survivors to achieve 5% weight compared to a self-directed approach, modulation of biomarkers of cancer risk including metabolism, inflammation, and telomere length, and changes in patient-reported outcomes.While levels of inflammatory cytokines improved, changes were not statistically significant. However, studies show that weight loss of 10% has been associated with modulation of serum and tissue biomarkers, such as Ki-67, adiponectin, adiponectin to leptin ratio, sex hormone binding globulin, estradiol, testosterone and insulin.The Sheng Research Team concluded in their Oncotarget Research Output that as there may be barriers to in-person or group interventions and studies aim for scalability, we can expect remote interventions like POWER-remote to be used as a practical strategy for weight loss.Remote strategies that incorporate a comprehensive assessment and coaching are necessary to ensure safe and cost effective treatment for cancer survivors struggling with weight loss.Sign up for free Altmetric alerts about this article - Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27898DOI - https://doi.org/10.18632/oncotarget.27898Correspondence to - Jennifer Y. Sheng - [email protected]Keywords - breast cancer, obesity, lifestyle interventionsAbout OncotargetOncotarget is a 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, LLC1 min
- Innovating & Expanding Weight Loss Strategies for Breast Cancer SurvivorsOncotarget published "Innovating and expanding weight loss strategies for breast cancer survivors" which reported that overweight and obesity are prevalent in over two thirds of the general population in the United States and are associated with an increased risk of malignancies, including breast cancer.This weight gain may increase risk of recurrence by 40–50%, and breast cancer-related mortality by 53–60% . Obesity at and following a breast cancer diagnosis is associated with poor quality of life and increased risk of adverse treatment effects.Dr. Jennifer Y. Sheng from The Johns Hopkins Sidney Kimmel Comprehensive Cancer Center said, "...survivorship guidelines recommend that weight loss should be a priority for overweight/obese survivors."Numerous clinical trials have tested behavioral strategies for weight loss in survivors of early stage breast cancer, including modifications in diet, remote or group interventions. These authors evaluated several outcomes including: whether a 12-month remotely delivered behavioral weight loss intervention allows a greater proportion of breast cancer survivors to achieve 5% weight compared to a self-directed approach, modulation of biomarkers of cancer risk including metabolism, inflammation, and telomere length, and changes in patient-reported outcomes.While levels of inflammatory cytokines improved, changes were not statistically significant. However, studies show that weight loss of 10% has been associated with modulation of serum and tissue biomarkers, such as Ki-67, adiponectin, adiponectin to leptin ratio, sex hormone binding globulin, estradiol, testosterone and insulin.The Sheng Research Team concluded in their Oncotarget Research Output that as there may be barriers to in-person or group interventions and studies aim for scalability, we can expect remote interventions like POWER-remote to be used as a practical strategy for weight loss.Remote strategies that incorporate a comprehensive assessment and coaching are necessary to ensure safe and cost effective treatment for cancer survivors struggling with weight loss.Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27898DOI - https://doi.org/10.18632/oncotarget.27898Correspondence to - Jennifer Y. Sheng - [email protected]Keywords - breast cancer, obesity, lifestyle interventionsAbout OncotargetOncotarget is a 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/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - 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
- Testimonial: Dr. Gina Abdelaal from Northumbria UniversityOncotarget published "Reversing oncogenic transformation with iron chelation" which reported that cancer cells accumulate iron to supplement their aberrant growth and metabolism.Depleting cells of iron by iron chelators has been shown to be selectively cytotoxic to cancer cells in vitro and in vivo. A plethora of studies have shown iron chelators can reverse some of the major hallmarks and enabling characteristics of cancer. Iron chelators inhibit signalling pathways that drive proliferation, migration and metastasis as well as return tumour suppressive signalling. Iron chelators target cancer cell metabolism, attenuating oxidative phosphorylation and glycolysis.Dr. Gina Abdelaal from The Northumbria University said, "Iron is vital for normal cell growth and survival."Cancer is an evolutionary maverick, which exploits its trademark genomic instability to drain environmental resources. As an enzyme cofactor, iron is responsible for many cellular processes including mitochondrial metabolism and DNA synthesis. As iron can drive cellular proliferation, cancer cells have an adapted iron metabolism allowing increased iron accumulation. The thiosemicarbazone class is a later stage of iron chelator evolution which manifested in 1992.Unlike their predecessor DFO, thiosemicarbazone chelators are capable of inducing reactive oxygen species. Triapine is a thiosemicarbazone; its primary mode of action is thought to be ribonucleotide reductase inhibition with a higher potency than commonly used ribonucleotide reductase inhibitor, hydroxyurea. This approach is predicted to protect healthy tissues from the cytotoxic effects as the timing and place of the drug release can be controlled.Encapsulating Dp44mT in PLGA nanoparticles enhanced its ability to induce apoptosis and improved its selectivity towards cancer cells.At present many more classes of iron chelators are being taken into consideration as potential cancer therapy candidates.The Abdelaal Research Team concluded in their Oncotarget Research Output that based on the data presented in this review iron chelators could potentially reverse many of the key hallmarks of cancer. Stripping the cells of iron impacts many cellular targets with some targets still undiscovered. NDRG1 has been proven to be the common link between the ability of iron chelators to reverse many of the hallmarks of cancer as overexpression of NDRG1 mimics the impact of iron chelation on several signalling pathways. There are still many unanswered questions about the mechanism of action of iron chelators.A consensus must be reached on the impact of iron chelation on angiogenesis through in vivo studies. As STAT3 is essential for VEGF gene expression and iron chelation attenuates STAT3 dimerisation and nuclear localisation. The cleaved isoform is only present in cancer cells and could potentially be oncogenic. Although many mechanistic studies have been undertaken iron chelators, the complexity of cell signalling remains a hurdle preventing the discovery of all cellular targets of iron chelation. A potential way of discovering new targets is combining iron chelators with well-characterised cancer therapeutics.DOI - https://doi.org/10.18632/oncotarget.27866Full text - https://www.oncotarget.com/article/27866/text/Correspondence to - Gina Abdelaal - [email protected]Keywords - iron chelator, oncogenesis, selective cytotoxicity, hallmarks of cancer, NDRG1About OncotargetOncotarget is a 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/2 min
- Reversing Oncogenic Transformation With Iron ChelationOncotarget published "Reversing oncogenic transformation with iron chelation" which reported that cancer cells accumulate iron to supplement their aberrant growth and metabolism.Depleting cells of iron by iron chelators has been shown to be selectively cytotoxic to cancer cells in vitro and in vivo. A plethora of studies have shown iron chelators can reverse some of the major hallmarks and enabling characteristics of cancer. Iron chelators inhibit signalling pathways that drive proliferation, migration and metastasis as well as return tumour suppressive signalling. Iron chelators target cancer cell metabolism, attenuating oxidative phosphorylation and glycolysis.Dr. Gina Abdelaal from The Northumbria University said, "Iron is vital for normal cell growth and survival."Cancer is an evolutionary maverick, which exploits its trademark genomic instability to drain environmental resources. As an enzyme cofactor, iron is responsible for many cellular processes including mitochondrial metabolism and DNA synthesis. As iron can drive cellular proliferation, cancer cells have an adapted iron metabolism allowing increased iron accumulation. The thiosemicarbazone class is a later stage of iron chelator evolution which manifested in 1992.Unlike their predecessor DFO, thiosemicarbazone chelators are capable of inducing reactive oxygen species. Triapine is a thiosemicarbazone; its primary mode of action is thought to be ribonucleotide reductase inhibition with a higher potency than commonly used ribonucleotide reductase inhibitor, hydroxyurea. This approach is predicted to protect healthy tissues from the cytotoxic effects as the timing and place of the drug release can be controlled.Encapsulating Dp44mT in PLGA nanoparticles enhanced its ability to induce apoptosis and improved its selectivity towards cancer cells.At present many more classes of iron chelators are being taken into consideration as potential cancer therapy candidates.The Abdelaal Research Team concluded in their Oncotarget Research Output that based on the data presented in this review iron chelators could potentially reverse many of the key hallmarks of cancer. Stripping the cells of iron impacts many cellular targets with some targets still undiscovered. NDRG1 has been proven to be the common link between the ability of iron chelators to reverse many of the hallmarks of cancer as overexpression of NDRG1 mimics the impact of iron chelation on several signalling pathways. There are still many unanswered questions about the mechanism of action of iron chelators.A consensus must be reached on the impact of iron chelation on angiogenesis through in vivo studies. As STAT3 is essential for VEGF gene expression and iron chelation attenuates STAT3 dimerisation and nuclear localisation. The cleaved isoform is only present in cancer cells and could potentially be oncogenic. Although many mechanistic studies have been undertaken iron chelators, the complexity of cell signalling remains a hurdle preventing the discovery of all cellular targets of iron chelation. A potential way of discovering new targets is combining iron chelators with well-characterised cancer therapeutics.DOI - https://doi.org/10.18632/oncotarget.27866Full text - https://www.oncotarget.com/article/27866/text/Correspondence to - Gina Abdelaal - [email protected]Keywords - iron chelator, oncogenesis, selective cytotoxicity, hallmarks of cancer, NDRG1About OncotargetOncotarget is a 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/12 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/