A new research perspective was published in Oncotarget's Volume 14 on May 19, 2023, entitled, “Targeting the Src N-terminal regulatory element in cancer.”

The signaling pathways displayed by cancer cells are often composed of the same components as the physiological ones, yet the overall result is a pathological deregulation. In this new paper, researchers Betlem Mezquita, Marjorie Reyes-Farias and Miquel Pons from the Universitat de Barcelona and Universitat Internacional de Catalunya discuss the non-receptor protein tyrosine kinase Src as a good example. 

“Src, the first discovered oncogene, is the leading member of the Src family of kinases (SFK) that includes Fyn, Yes, Blk, Yrk, Fgr, Hck, Lck, and Lyn.”

Src is the first described proto-oncogene and a demonstrated player in cancer progression, as it affects proliferation, invasion, survival, cancer stemness, and drug resistance. Src activation is linked to poor prognosis in many cancer types, yet mutations in this protein are rarely observed. In addition, being a demonstrated cancer target, unspecific inhibition of the kinase activity has proven inefficient in clinics since the inhibition of Src in non-cancerous cells results in unacceptable toxicity. 

Thus, there is a need for new target regions in Src that could inhibit Src activity only in certain cell types, e.g., cancer cells, while maintaining the normal physiological activity in healthy cells. The Src N-terminal regulatory element (SNRE) includes the poorly studied intrinsically disordered region with unique sequences for each of the members of the Src family. In this perspective, the researchers discuss the non-canonical regulatory mechanisms involving the SNRE and their potential use as oncotargets.

“Our group has designed a screening system to search chemical libraries for binders of the Src SNRE [88] and we are currently following up a promising lead.”

DOI: https://doi.org/10.18632/oncotarget.28434 

Correspondence to: Miquel Pons - mpons@ub.edu 

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Keywords: Src family kinases, intrinsically disordered proteins, SNRE, cell-type selective drugs, drug resistance

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. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Oncotarget

Targeting the Src N-Terminal Regulatory Element in Cancer

BUFFALO, NY- May 22, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 9, entitled, “Cell type-dependent modulation of senescence features using Weo electrolyzed water.”

Electrolyzed-reduced water has powerful antioxidant properties with constituents that scavenge reactive oxygen species (ROS), which are known to be produced by several intrinsic and extrinsic processes. When there is an imbalance between ROS production and antioxidant defenses, oxidative stress occurs. Persistent oxidative stress leads to cellular senescence, an important hallmark of aging, and is involved in several age-related conditions and illnesses. 

In this new study, researchers Brenda L. Court-Vazquez, Shirley A. Arroyo-Vizcarrondo, Jonathan A. Poli, Lara Nyman, Kelly Halderman, Anthony Ginter, and Pierre-Yves Desprez from Weo LLC and California Pacific Medical Center investigated whether Weo electrolyzed water (WEW) could modulate the phenotype of senescent cells. 

“The focus of this study was to utilize two different cell types, human normal fibroblasts and human breast cancer cells, to investigate the impact of Weo electrolyzed water (WEW) on markers of cellular senescence, inflammation, and stress response genes.”

The researchers compared normal human lung fibroblasts (BJ) and breast cancer cells (T47D) treated with hydrogen peroxide (H2O2) to induce senescence. They assessed the molecular impact of WEW on markers of cellular senescence, senescence-associated secretory phenotype (SASP) factors, and stress response genes. Treatment with WEW modulated markers of cellular senescence, such as the senescence-associated β-galactosidase (SA-β-gal) activity, EdU incorporation and p21 expression, similarly in both cell types. 

However, WEW modulated the expression of SASP factors and stress response genes in a cell type-dependent and opposite fashion, significantly decreasing them in BJ cells, while stimulating their expression in T47D cells. Reduction in the expression of SASP factors and stress-related genes in BJ cells suggests that WEW acts as a protective factor, thereby reducing oxidative stress in normal cells, while making cancer cells more sensitive to the effects of cellular stress, thus increasing their elimination and consequently reducing their deleterious effects. 

“In conclusion, we have shown here that the new technology developed by Weo, WEW, could attenuate the overall process of cellular senescence in both normal BJ fibroblasts and cancer T47D cells.”

DOI - https://doi.org/10.18632/aging.205789

Corresponding authors - Brenda L. Court-Vazquez - bco@we-o.com, and Pierre-Yves Desprez - pydesprez@cpmcri.org

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Keywords - aging, cellular senescence, senescence-associated secretory phenotype, oxidative stress, lung fibroblasts, breast cancer cells, senomorphic

About Aging-US

Aging publishes research papers in all fields of aging research, including but not limited to aging processes (from yeast to mammals), cellular senescence, age-related diseases (such as cancer and Alzheimer’s disease) and their prevention and treatment, anti-aging strategies and drug development, and, importantly, the role of signal transduction pathways in aging (such as mTOR) and potential approaches to modulate these signaling pathways to extend lifespan.

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Aging (Aging-US)

Modulation of Senescence Features Using Weo Electrolyzed Water

In this episode, Dr. Ron George provides a tour de force of our past and present labor analgesia management. We discuss his recent publication, Modern Labor Epidural Analgesia: Implications for Labor Outcomes and Maternal-Fetal Health.
https://pubmed.ncbi.nlm.nih.gov/37164496/
The Most Influential Publications in Obstetric Anesthesiology, 1998–2017: Utilizing the Delphi Method for Expert Consensus
https://pubmed.ncbi.nlm.nih.gov/32282388/
Effect of low-dose mobile versus traditional epidural techniques on mode of delivery: a randomised controlled trial
https://pubmed.ncbi.nlm.nih.gov/11454372/
A comparison of a basal infusion with automated mandatory boluses in parturient-controlled epidural analgesia during labor
https://pubmed.ncbi.nlm.nih.gov/17312228/
The risk of cesarean delivery with neuraxial analgesia given early versus late in labor
https://pubmed.ncbi.nlm.nih.gov/15716559/

Modern Labor Epidural Analgesia

Executive Director of El Hogar Denise Vargas joins us to talk about entrepreneurship. She helps us think in an entrepreneurial way about ministry and grounds innovation in community. We also take a while to chat about Vargas’s life as a poet, to hear some of her poetry, and to talk about how poetry intersects with the work she does at El Hogar.

22: Entrepreneurship with Denise Vargas

Professors Amy Carr and Christine Helmer join Hannah to talk about their new, timely book, Ordinary Faith in Polarized Times: Justification and the Pursuit of Justice. We take a moment in this season leading up to the presidential election to discuss high-conflict times and how we can move toward good conflict. We talk about how Christians can create space for conversation because of their status of belonging due to justification. We discuss how Christians can listen to each other, discuss hot-button issues, and navigate difference.

23: Ordinary Faith in Polarized Times with Amy Carr and Christine Helmer

Upon diagnosing acute myeloid leukemia (AML), the initial step involves assessing a patient’s eligibility for intensive chemotherapy. The standard treatment protocol for newly diagnosed AML encompasses intensive chemotherapy to achieve complete remission, followed by post-remission therapy, which may include additional chemotherapy and/or stem cell transplantation. Complete response rates to this approach range from 60% to 85% in adults aged 60 or younger.

While this approach has proven effective, the risk of relapse within three years of diagnosis remains a significant concern. Numerous factors contribute to the likelihood of relapse, including short duration of remission, genetic derangements, prior allogeneic transplantation, advanced age, and concomitant comorbidities. These negative prognostic factors underscore the need for continuous exploration of novel therapeutic agents, as relapse remains a formidable barrier to treatment success.

In a new study, researchers Simonetta I. Gaumond, Rama Abdin, Joel Costoya, Andrew V. Schally (awarded the Nobel Prize in Physiology or Medicine in 1977), and Joaquin J. Jimenez from the University of Miami, Florida Atlantic University and Veterans Affairs Medical Center, Miami, investigated newly emerging therapies targeting drug resistance in AML. On April 8, 2024, their new research paper was published in Oncotarget’s Volume 15, entitled, “Exploring the role of GHRH antagonist MIA-602 in overcoming Doxorubicin-resistance in acute myeloid leukemia.”

Full blog - https://www.oncotarget.org/2024/05/23/combating-doxorubicin-resistant-acute-myeloid-leukemia/

Paper DOI - https://doi.org/10.18632/oncotarget.28579

Correspondence to - Simonetta I. Gaumond - sxg1204@miami.edu

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Keywords - cancer, leukemia, AML, resistance, growth hormone-releasing hormone, MIA-602

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.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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Combating Doxorubicin-Resistant Acute Myeloid Leukemia

BUFFALO, NY- May 28, 2024 – A new review paper was published in Oncotarget's Volume 15 on May 23, 2024, entitled, “The importance of integrated therapies on cancer: Silibinin, an old and new molecule.”

In this new review, researchers Elisa Roca, Giuseppe Colloca, Fiorella Lombardo, Andrea Bellieni, Alessandra Cucinella, Giorgio Madonia, Licia Martinelli, Maria Elisa Damiani, Ilaria Zampieri, and Antonio Santo from Perderzoli Hospital and Fondazione Policlinico Universitario “A. Gemelli” begin their abstract by noting that the efficacy of coadjuvant molecules, in the landscape of cancer treatments, remains a focus of attention for clinical research with the aim of reducing toxicity and achieving better outcomes.

“Most of the pathogenetic processes causing tumour development, neoplastic progression, ageing, and increased toxicity involve inflammation.”

Inflammatory mechanisms can progress through a variety of molecular patterns. As is well known, the ageing process is determined by pathological pathways very similar and often parallel to those that cause cancer development. Among these complex mechanisms, inflammation is currently much studied and is often referred to in the geriatric field as ‘inflammaging’. In this context, treatments active in the management of inflammatory mechanisms could play a role as adjuvants to standard therapies.

Among these emerging molecules, Silibinin has demonstrated its anti-inflammatory properties in different neoplastic types, also in combination with chemotherapeutic agents. Moreover, this molecule could represent a breakthrough in the management of age-related processes. Thus, Silibinin could be a valuable adjuvant to reduce drug-related toxicity and increase therapeutic potential.

“For this reason, the main aim of this review is to collect and analyse data presented in the literature on the use of Silibinin, to better understand the mechanisms of the functioning of this molecule and its possible therapeutic role.”

DOI - https://doi.org/10.18632/oncotarget.28587

Correspondence to - Elisa Roca - elisaroca@gmail.com

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Keywords - cancer, silibinin, anti-inflammatory, inflammation, toxicity, integrated therapy

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.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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MEDIA@IMPACTJOURNALS.COM

The Importance of Integrated Therapies on Cancer: Silibinin, an Old and New Molecule

Dr. Benoit Chabot from Université de Sherbrooke in Quebec, CA, discusses a research paper he co-authored that was published by Oncotarget in Volume 15, entitled, “The anticancer potential of the CLK kinases inhibitors 1C8 and GPS167 revealed by their impact on the epithelial-mesenchymal transition and the antiviral immune response.”

DOI - https://doi.org/10.18632/oncotarget.28585

Correspondence to - Benoit Chabot - benoit.chabot@usherbrooke.ca

Abstract

The diheteroarylamide-based compound 1C8 and the aminothiazole carboxamide-related compound GPS167 inhibit the CLK kinases, and affect the proliferation of a broad range of cancer cell lines. A chemogenomic screen previously performed with GPS167 revealed that the depletion of components associated with mitotic spindle assembly altered sensitivity to GPS167. Here, a similar screen performed with 1C8 also established the impact of components involved in mitotic spindle assembly. Accordingly, transcriptome analyses of cells treated with 1C8 and GPS167 indicated that the expression and RNA splicing of transcripts encoding mitotic spindle assembly components were affected. The functional relevance of the microtubule connection was confirmed by showing that subtoxic concentrations of drugs affecting mitotic spindle assembly increased sensitivity to GPS167. 1C8 and GPS167 impacted the expression and splicing of transcripts in pathways relevant to tumor progression, including MYC targets and the epithelial mesenchymal transition (EMT). Finally, 1C8 and GPS167 altered the expression and alternative splicing of transcripts involved in the antiviral immune response. Consistent with this observation, depleting the double-stranded RNA sensor DHX33 suppressed GPS167-mediated cytotoxicity on HCT116 cells. Our study uncovered molecular mechanisms through which 1C8 and GPS167 affect cancer cell proliferation as well as processes critical for metastasis.

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Keywords - cancer, CLK kinases inhibitors, EMT, antiviral immune response, microtubules, metastasis

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.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital 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/oncotarget
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MEDIA@IMPACTJOURNALS.COM

Behind the Study: Anticancer Potential of CLK Kinase Inhibitors 1C8 and GPS167

In this episode, Dr. Allison Mootz, an obstetric anesthesiology fellow at Brigham and Women, discusses her thought-provoking article titled- The Accuracy of ChatGPT-Generated Responses in Answering Commonly Asked Patient Questions About Labor Epidurals: A Survey-Based Study. 
https://pubmed.ncbi.nlm.nih.gov/38180897/
Comparing Physician and Artificial Intelligence Chatbot Responses to Patient Questions Posted to a Public Social Media Forum
https://pubmed.ncbi.nlm.nih.gov/37115527/

Accuracy of ChatGPT

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/

Targeting the Src N-Terminal Regulatory Element in Cancer

Oncotarget Podcast

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