BUFFALO, NY- August 8, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on August 5, 2024, entitled, “Chemical complementarity of tumor resident, T-cell receptor CDR3s and renalase-1 correlates with increased melanoma survival.”

As mentioned in the Abstract of this study, overexpression of the secretory protein renalase-1 negatively impacts the survival of melanoma and pancreatic cancer patients, while inhibition of renalase-1 signaling drives tumor rejection by promoting T-cell activation. 

Thus, researchers Saif Zaman, Fred S. Gorelick, Andrea Chrobrutskiy, Boris I. Chobrutskiy, Gary V. Desir, and George Blanck from Yale School of Medicine, Veteran’s Administration Healthcare System, Oregon Health and Science University Hospital, Morsani College of Medicine, and H. Lee Moffitt Cancer Center and Research Institute, investigated the chemical complementarity between melanoma-resident, T-cell receptor (TCR) complementarity-determining region 3 (CDR3) amino acid sequences (AAs) and the renalase-1 protein.

“In this study, we asked whether the RNLS protein could potentially be a tumor antigen by examining chemical complementarity between melanoma tumor-resident TCR CDR3s and the AA sequence of RNLS.”

The results suggest that there could be biologically relevant antigenic interaction between RNLS epitopes and T-cell receptors (TCRs).

“We hypothesize that RNLS protein could be recognized by TCRs, leading to local immune responses against melanoma, similar to what we have previously demonstrated with wildtype cancer antigens in the melanoma and glioblastoma settings.”

DOI - https://doi.org/10.18632/oncotarget.28633

Correspondence to - George Blanck - gblanck@usf.edu

Video short - https://www.youtube.com/watch?v=p3X9IgPQFJw

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Keywords - cancer, RNLS, melanoma, T-cell receptor CDR3s, chemical complementarity

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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Oncotarget

TCR CDR3s and Renalase-1 Linked to Increased Melanoma Survival

BUFFALO, NY- August 14, 2024 – A new #casereport was #published in Oncotarget's Volume 15 on July 17, 2024, entitled, “Rapid but nondurable response of a BRAF exon 15 double-mutated spindle cell sarcoma to a combination of BRAF and MEK inhibitors.”

As noted in the introduction of the Abstract, the BRAF V600E substitution predicts a cancer's sensitivity to BRAF inhibitor therapy, though the mutation is rarely found in soft-tissue sarcomas.

Researchers Kseniya Sinichenkova, Iliya Sidorov, Nataliya Kriventsova, Dmitriy Konovalov, Ruslan Abasov, Nataliya Usman, Alexander Karachunskiy, Galina Novichkova, Dmitriy Litvinov, and Alexander Druy from the Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology (Ministry of Healthcare of Russian Federation) and the Research Institute of Medical Cell Technologies in Yekaterinburg, Russia, describe a case of undifferentiated spindle cell sarcoma that exhibited primary insensitivity to standard chemotherapy and a pronounced but non-sustained response to BRAF/MEK inhibitors at recurrence.

The case presentation involved a 13-year-old girl that was diagnosed with low-grade spindle cell sarcoma of pelvic localization, BRAF exon 15 double-mutated: c.1799T>A p.V600E and c.1819T>A p.S607T in cis-position. 

“This is the first report of spindle cell sarcoma BRAF V600E/S607T double-mutated, responding to a combination of B-Raf and MEK inhibitors.”

DOI - https://doi.org/10.18632/oncotarget.28606

Correspondence to - Kseniya Sinichenkova - ksinichenkova@gmail.com

Video short - https://www.youtube.com/watch?v=QWEAaaixPxE

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Keywords - cancer, undifferentiated sarcoma, BRAF V600E mutation, low grade spindle cell sarcoma, abdominal cocoon

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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Response of BRAF-Mutated Spindle Cell Sarcoma to BRAF/MEK Inhibitors

BUFFALO, NY- August 21, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on July 17, 2024, entitled, “Strategies to disrupt NKG2A:HLA-E interactions for improved anti-cancer immunity.”

Two studies using CRISPR screens in cancer cells identified HLA-E as a critical negative regulator of NK cell interactions with cancer cells. Consistent with this, IFNγ signaling was associated with NK cell resistance due to increased STAT1 activation and enhanced HLA-E expression. This effect is also evident in the murine homolog of HLA-E, Qa-1b, which was upregulated by inflammatory signals across all cell types tested.

In addition to inflammatory signals, researchers Jack G. Fisher, Lara V. Graham, and Matthew D. Blunt from Clinical and Experimental Sciences, Faculty of Medicine at the University of Southampton, UK, recently demonstrated that surface expression of HLA-E is increased by lymph node-associated signals IL-4 and CD40L on primary chronic lymphocytic leukaemia (CLL) cells.

Additionally, two recent studies have shown that HLA-E can protect circulating tumor cells from NK cell lysis via NKG2A, suggesting that targeting the NKG2A axis could be a promising strategy for preventing metastasis in solid tumors.

“In conclusion, there is strong preclinical evidence that disruption of NKG2A interactions with HLA-E can stimulate both NK cell and cytotoxic T cell effector functions against cancer.”

DOI - https://doi.org/10.18632/oncotarget.28610

Correspondence to - Matthew D. Blunt - m.d.blunt@soton.ac.uk

Video short - https://www.youtube.com/watch?v=iQREIa-RToU

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Keywords - cancer, Natural killer (NK) cells, immunotherapy, NKG2A, immune checkpoint blockade, HLA-E

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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Disrupting NKG2A:HLA-E Interactions for Enhanced Anti-Cancer Immunity

BUFFALO, NY- October 21, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on October 1, 2024, entitled, “Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition.”

As highlighted in the abstract, monoclonal antibody therapies for cancer have shown extraordinary clinical success in recent years. However, these strategies are primarily limited to targeting specific cell surface antigens, despite many disease targets being located intracellularly.

In their paper, researchers Madison Rackear, Elias Quijano, Zaira Ianniello, Daniel A. Colón-Ríos, Adam Krysztofiak, Rashed Abdullah, Yanfeng Liu, Faye A. Rogers, Dale L. Ludwig, Rohini Dwivedi, Franziska Bleichert, and Peter M. Glazer from the Departments of Therapeutic Radiology and Genetics at Yale University School of Medicine, Gennao Bio, and the Department of Molecular Biophysics and Biochemistry at Yale University report on the humanization of the full-length, nucleic acid-binding monoclonal lupus-derived autoantibody 3E10, which exhibits a novel mechanism for cell penetration and tumor-specific targeting.

The authors compare humanized variants of 3E10 and demonstrate that cell uptake relies on the nucleoside transporter ENT2. They also find that faster cell uptake and superior in vivo tumor targeting are associated with higher affinity nucleic acid binding.

“We show that one human variant retains the ability of the parental 3E10 to bind RAD51, serving as a synthetically lethal inhibitor of homology-directed repair in vitro.”

DOI - https://doi.org/10.18632/oncotarget.28651

Correspondence to - Peter M. Glazer - peter.glazer@yale.edu

Video short - https://www.youtube.com/watch?v=sTHjJ0Qq0YQ

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Keywords - cancer, 3E10, cell penetration, nucleic acid binding, nucleic acid delivery, RAD51

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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Next-Gen Cell-Penetrating Antibodies for Tumor Targeting and RAD51 Inhibition

Cancer research has made remarkable progress in recent years, with monoclonal antibody (mAb) therapy emerging as one of the most promising advancements. These treatments are designed to precisely target cancer cells, offering a more focused approach that helps patients fight different malignancies with fewer side effects compared to traditional chemotherapy.

Despite this progress, a major challenge remains: targeting cancer-related molecules inside cells rather than on the surface, which has been the main focus of available mAb therapies until now. This is where the groundbreaking research in the paper “Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition,” published in Volume 15 of Oncotarget on October 1, 2024, comes into play.

Full blog - https://www.oncotarget.org/2024/10/24/next-generation-antibodies-for-cancer-therapy/

Paper DOI - https://doi.org/10.18632/oncotarget.28651

Correspondence to - Peter M. Glazer - peter.glazer@yale.edu

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Keywords - cancer, 3E10, cell penetration, nucleic acid binding, nucleic acid delivery, RAD51

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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Next-Generation Antibodies for Cancer Therapy

Beat by :

https://on.soundcloud.com/au9hnzwcvpErDUbE8

lyrics:

chorus
dead braincells in my head
sorry to mom for the moments i forget
i cant describe how its feel
to lost some time from my mind

dead braincells in my head
sorry to mom for the moments i forget
i cant describe how its feel
to lost some time from my mind

verse
met my schoollove
i forgot whats her name
and my schoollove
ye she think im the same

but the time brought changes in my life, lost memories
after psychiatry feelin like empty gallery

so many situations i don't remember
burning cells in my head, guess no one surrendered
friends ask me bout moments, i dont know what to say
a lie is all what i can say

chorus
dead braincells in my head
sorry to mom for the moments i forget
i cant describe how its feel
to lost some time from my mind

dead braincells in my head
sorry to mom for the moments i forget
i cant describe how its feel
to lost some time from my mind

braincells

BUFFALO, NY - November 12, 2024 – A new #review was #published in Oncotarget's Volume 15 on November 7, 2024, entitled “Understanding the interplay between extracellular matrix topology and tumor-immune interactions: Challenges and opportunities.”

This comprehensive review by researchers Yijia Fan, Alvis Chiu, Feng Zhao, and Jason T. George from Texas A&M University, Rice University, and MD  Anderson Cancer Center sheds light on how the structural properties of the extracellular matrix (ECM) within tumors impact immune cell behavior and influence the effectiveness of cancer immunotherapies. The ECM, a network of proteins surrounding cells, often transforms in cancer, becoming denser and more aligned. These changes create physical barriers that can prevent immune cells, especially T cells, from effectively accessing and attacking tumors, thereby limiting the success of immunotherapies.

The team emphasizes the role of specific ECM configurations, known as Tumor-Associated Collagen Signatures (TACS), in cancer progression and immune evasion. TACS1 and TACS2 patterns create "immune deserts" around tumors, limiting immune cell movement and preventing T cells from recognizing and attacking cancer cells, which is essential for successful immunotherapy. In advanced stages, TACS3 aligns ECM fibers in ways that both promote tumor spread and create additional barriers, further obstructing immune cell access to the tumor.

These insights lead the way for ECM-targeted therapies designed to modify these barriers, potentially transforming “cold” (immune-non-responsive) tumors into “hot” (immune-responsive) ones, thereby improving immune cell infiltration and enhancing treatment outcomes. 

“Understanding the complex interplay is relevant for developing more accurate model of tumor evasion and the identification of corresponding therapeutic intervention.”


The review highlights advanced computational models that simulate interactions between the ECM, immune cells, and tumors, offering valuable insights for developing ECM-targeted therapies. These models illustrate how modifying ECM properties could enhance immune cell migration and function, potentially overcoming immune resistance and expanding the effectiveness of immunotherapies.

The authors also suggest that targeting ECM structure could significantly enhance the effectiveness of immunotherapy, especially for cancers like breast, pancreatic, and ovarian, which often feature dense ECM regions. By reshaping the ECM, such treatments could enable immune cells to access previously unreachable tumor areas, presenting a promising strategy to combat tumors that are resistant to standard therapies.

In conclusion, the review underscores the need for continued research into ECM-focused strategies, which could support more integrated approaches to cancer treatment. By targeting the ECM’s physical barriers and immune evasion mechanisms, these strategies hold promise for improving outcomes in difficult-to-treat cancers.

DOI - https://doi.org/10.18632/oncotarget.28666

Correspondence to - Jason T. George - jason.george@tamu.edu

Video short - https://www.youtube.com/watch?v=7Wm-SMLJadk

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Extracellular Matrix and Tumor-Immune Interactions: Challenges & Opportunities

BUFFALO, NY- November 13, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), on October 25, 2024, Volume 16, Issue 20, titled, ”Canonical ligand-dependent and non-canonical ligand-independent EphA2 signaling in the eye lens of wild-type, knockout, and aging mice.“

Researchers from the School of Optometry and Vision Science Program at Indiana University have uncovered important new insights into how the aging affects the eye lens and contributes to cataract formation, a condition impacting millions worldwide. This study focuses on the EphA2 protein, traditionally associated with cancer, which researchers have now identified as essential for maintaining the lens’s clarity and function as it ages.

Cataracts are the leading cause of blindness worldwide, primarily affecting older adults, yet the precise biological mechanisms behind their formation remain unclear. This research sheds light on the role of the EphA2 protein receptor in the eye lens, revealing that it operates through two distinct signaling pathways: a canonical (ligand-dependent) and a non-canonical (ligand-independent) pathway. By studying various groups of mice, including those lacking the EphA2 protein receptor and its ligand partner ephrin-A5, scientists observed how these signaling pathways change with age, affecting the organization and maturation of lens cells.

Researchers Jenna L. Horner, Michael P. Vu, Jackson T. Clark, Isaiah J. Innis, and Catherine Cheng observed that EphA2’s canonical signaling, which organizes lens cells, remains stable in aging lens tissue, particularly in epithelial cells. They found that the non-canonical signaling pathway—previously associated primarily with aggressive cancer cells—increases with age in normal lens cells. This increase suggests that non-canonical signaling plays a crucial role in helping lens fiber cells mature and maintain their structure over time.

“Here, we report that canonical ligand-mediated EphA2 activation is restricted to the lens epithelial cells and show the first evidence of physiological non-canonical EphA2 activity in a normal tissue.”

This understanding could lead to new therapies targeting EphA2 to delay or prevent cataracts.

In conclusion, this study represents a significant advance in understanding the cellular mechanisms behind lens aging and cataract development, potentially paving the way for new non-surgical cataract treatments.

DOI - https://doi.org/10.18632/aging.206144

Corresponding author - Catherine Cheng - ckcheng@iu.edu

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Keywords - aging, fiber cells, epithelial cells, Y588, Y589, S897, phosphorylation, maturation, ephrin

About Aging-US

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

Please visit our website at https://www.Aging-US.com​​ and connect with us:

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Aging (Aging-US)

EphA2 Signaling in Eye Lens Aging: Wild-Type, Knockout, and Aging Mice

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cold cells

Cell Cycle Harmony

This is the first track I wrote to test out the new Spitfire Audio Olafur Arnalds Cells library.  I added some Spitfire Jupter, Slate+Ash Primaries and Cycles, Pulse Audio Likkuva and Orchestral Tools Time Micro, Waverunner Audio Synth Atlantic, and Westwood Instruments Alt Piano to round it out.

From the First Cells

BUFFALO, NY - December 11, 2024 – A #news feature on the #research paper “Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition” by Rackear et al. was #published in Oncotarget's Volume 15 on November 22, 2024, titled “Advancements in cell-penetrating monoclonal antibody treatment."

This new publication by Sai Pallavi Pradeep and Raman Bahal from the  Department of Pharmaceutical Sciences at the University of Connecticut highlights significant advancements in monoclonal antibody (mAb) therapies. The focus is on the 3E10 antibody, originally derived from autoimmune mouse studies in systemic lupus erythematosus. Unlike traditional mAbs, which struggle to reach intracellular targets, this cell-penetrating antibody targets cancer cells by addressing a major limitation of current therapies. By targeting RAD51, a key intracellular protein involved in DNA repair, the 3E10 antibody shows great promise for cancer treatment, particularly in cancers with defective DNA repair pathways.

mAbs have already changed the landscape of cancer therapy, offering treatments that are more targeted and have fewer side effects compared to chemotherapy. However, current therapies are limited since mAbs only target proteins on the surface of cancer cells. This research pushes the boundaries by demonstrating how 3E10 antibodies can penetrate cells and access their internal molecules. This unique capability expands the potential of mAb therapies and targeted cancer treatments.

Different humanized versions of the 3E10 antibody were created and carefully tested. Some versions were particularly effective at blocking RAD51, while others showed promise for carrying other therapeutic molecules like genetic material into the cancer cells. This flexibility means that 3E10 could be used to treat different cancer types and deliver various therapeutic molecules directly into tumor cells. This progress offers exciting new possibilities for treating cancer tumors that are resistant to conventional therapies. 

In conclusion, the 3E10 antibody’s dual function—targeting DNA repair pathways and delivering therapeutic molecules—positions it as a transformative tool in cancer research and targeted cancer treatments.

DOI - https://doi.org/10.18632/oncotarget.28674

Correspondence to - Raman Bahal - raman.bahal@uconn.edu

Video short - https://www.youtube.com/watch?v=3uMdPvThFHA

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Keywords - cancer, monoclonal anti-bodies, cell penetration, nucleic acid delivery, 3E10

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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Breakthroughs in Cell-Penetrating Monoclonal Antibody Therapies

LISTEN MUSIC https://album.link/wnjfdck8dgpdf 🖤

LISTEN MUSIC🖤

Dead Skin Cells feat. Rottenscape - Transparent Death

Scientists have discovered that a genetic variant called KIT M541L may play an important role in a rare immune disorder known as #mastocytosis. The findings may help explain why some #patients develop more severe forms of the disease.

Understanding Mastocytosis

Mastocytosis is a condition where the body produces too many mast cells. These cells are part of the immune system and help the body fight infections, but in excess, they release chemicals that can cause itching, swelling, and even serious organ damage.

There are two main types of mastocytosis. The first is cutaneous mastocytosis, which mostly affects the skin. The second is systemic mastocytosis, a more serious form where mast cells build up in internal organs like the liver, spleen, and bone marrow.

The disease is linked to mutations in the KIT gene, which regulates mast cell growth. The most studied mutation is KIT D816V, but recent research has highlighted another variant, KIT M541L.

The Study: Impact of KIT M541L Variant

A team of researchers at the National Institutes of Health (NIH), led by first author Luisa N. Dominguez Aldama and corresponding author Melody C. Carter, aimed to better understand the prevalence and impact of the KIT M541L genetic variant in mastocytosis patients. The study published in Oncotarget on July 22, 2024, titled “Prevalence and impact of the KIT M541L variant in patients with mastocytosis,” examined the presence of the KIT M541L gene variant in 100 patients with mastocytosis, both adults and children, alongside 500 healthy individuals. 

By comparing these two groups, the researchers wanted to see if there was a relation between the KIT M541L variant and mastocytosis severity.

Full blog - https://www.oncotarget.org/2025/01/15/mastocytosis-key-insights-into-kit-m541l-gene-mutation/

Paper DOI - https://doi.org/10.18632/oncotarget.28614

Correspondence to - Melody C. Carter - mcarter@niaid.nih.gov

Video short - https://www.youtube.com/watch?v=zpiBbSfkTX4

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Keywords - cancer, mastocytosis, KIT M541L, KIT D816V, adults, pediatrics

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:

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MEDIA@IMPACTJOURNALS.COM

Mastocytosis: Key Insights into KIT M541L Gene Mutation

BUFFALO, NY - February 24, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on February 18, 2025, titled “Robust p53 phenotypes and prospective downstream targets in telomerase-immortalized human cells."

Researchers Jessica J. Miciak, Lucy Petrova, Rhythm Sajwan, Aditya Pandya, Mikayla Deckard, Andrew J. Munoz, and Fred Bunz from the Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine studied the tumor-suppressing protein p53, which plays a key role in preventing cancer. Their findings reveal how p53 affects cancer cell growth, treatment resistance, and potential drug targets, providing new insights that could improve future cancer therapies.

The p53 protein plays a crucial role in preventing cancer by stopping uncontrolled cell growth. However, many cancers mutate or suppress p53, allowing tumors to develop and resist treatment. In this study, researchers restored p53 function in colorectal cancer cells, which led to slower cellular growth, increased cellular aging (senescence), and greater sensitivity to radiation therapy. These findings suggest that p53 status influences cancer progression and response to treatment, making it a promising target for new therapies.

The study also examined hTERT-RPE1 cells; a type of non-cancerous human cell used in research. When the TP53 gene was disrupted in these cells, they grew faster and became more resistant to radiation, reinforcing the idea that p53 helps prevent cancerous growth.

Another key discovery was a previously unnoticed p53 mutation (A276P) found in a subset of hTERT-RPE1 cells. This mutation weakened p53’s ability to regulate certain genes but did not affect its ability to control calcium signaling, a process important for cell survival. The unexpected appearance of this mutation suggests that even non-cancerous cells can acquire genetic changes that mimic early cancer development. This insight could help scientists better understand how cancers evolve and become resistant to treatment.

"Cancers that retain wild type TP53 presumably harbor other clonal alterations that permitted their precursors to bypass p53-mediated growth suppression."

A breakthrough in the study was the identification of two new p53-regulated genes that could be important for cancer treatment. The first, ALDH3A1, helps detoxify harmful substances and may impact cancer cell resistance to oxidative stress. The second, NECTIN4, is a protein found in many aggressive cancers, including bladder and breast cancer. Notably, NECTIN4 is the target of enfortumab vedotin, an FDA-approved drug for bladder cancer. These discoveries provide new potential drug targets and could lead to improved therapies for cancers that still retain some p53 function.

In conclusion, this research highlights the critical role of p53 in cancer biology and suggests that restoring p53 function could make tumors more vulnerable to radiation and chemotherapy. The discovery of new p53-controlled genes provides new opportunities for targeted cancer therapies. With further research, these findings could lead to new precision medicine strategies that leverage p53’s natural tumor-suppressing abilities.

DOI - https://doi.org/10.18632/oncotarget.28690

Correspondence to - Fred Bunz - fredbunz@jhmi.edu

Video short - https://www.youtube.com/watch?v=Psxj3ctbTuk

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MEDIA@IMPACTJOURNALS.COM

Researchers Identify New p53 Targets to Combat Cancer Growth

I will never quit Sm0king #nicotine #kush - (DJ HEROIN EXCLUSIVE)

BUFFALO, NY - March 3, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on February 28, 2025, titled “Effect of TIMPs and their minimally engineered variants in blocking invasion and migration of brain cancer cells."

Elham Taheri and Maryam Raeeszadeh-Sarmazdeh from the University of Nevada, Reno, explored a new approach to slowing the spread of glioblastoma multiforme (GBM), the most aggressive and deadly form of brain cancer. Their study highlights the potential of both natural and engineered molecules to block cancer cell movement, offering a promising strategy to combat this challenging disease.

Glioblastoma multiforme is difficult to treat because it quickly spreads into healthy brain tissue, making complete surgical removal nearly impossible. A major driver of this invasive behavior is a group of enzymes called matrix metalloproteinases (MMPs), which break down surrounding tissue and create space for cancer cells to spread. Among them, MMP-9 plays a particularly significant role in GBM progression and resistance to current treatments.

To address this challenge, the researchers investigated tissue inhibitors of metalloproteinases (TIMPs), natural MMP blockers, and specially engineered versions designed for better effectiveness. The study used cell line models of GBM to test both TIMP-1 and TIMP-3 and their engineered counterparts (mTC1 and mTC3), specific blockers of MMP-9. 

“Our study focused on minimal TIMP variants, due to their small molecular size and potential in higher cellular uptake and delivery, to assess their potential in cell-based assays.”

The results indicated that the engineered TIMPs were just as effective as, or even better than, the natural ones at reducing cancer cell migration and invasion. These findings are particularly promising because previous attempts to block MMPs with small-molecule drugs faced challenges such as poor selectivity and unwanted side effects. In contrast, these engineered TIMPs offer a more targeted and potentially safer approach.

One of the greatest obstacles in treating brain cancer is delivering drugs across the blood-brain barrier, a protective layer that prevents many therapeutic compounds from reaching the brain. To address this, the researchers used cell-penetrating peptides to help the TIMP variants reach and enter cancer cells more effectively. Their results confirmed that the engineered TIMPs successfully reached tumor cells, further increasing their potential as a treatment.

Additionally, the study found that these engineered TIMPs did not significantly affect healthy cells at lower doses, suggesting they could be used safely. This makes them strong candidates for further drug development.

These findings could lead to new treatment options for GBM, a cancer with very few effective therapies. Future research will focus on testing these TIMP variants in animal models to evaluate their long-term effects and safety. Researchers also plan to investigate whether combining these engineered TIMPs with existing treatments, such as chemotherapy or immunotherapy, could improve outcomes.

In summary, given the aggressive nature of GBM and the urgent need for better therapies, this study represents an important step forward. If further research confirms these results, engineered TIMPs could become a valuable tool in the fight against brain cancer, offering new hope for improved treatments and patient survival.

DOI - https://doi.org/10.18632/oncotarget.28691

Correspondence to - Maryam Raeeszadeh-Sarmazdeh - maryamr@unr.edu

Video short - https://www.youtube.com/watch?v=tdBlkOX50D8

To learn more about Oncotarget, please visit https://www.oncotarget.com.

MEDIA@IMPACTJOURNALS.COM

Engineered TIMP Molecules Show Potential to Slow Glioblastoma Brain Cancer Spread

Chris Holman welcomes Chris Miller, SIOR, Senior Vice President, Martin Commercial Properties, Lansing, MI.

This discussion is the first of three with Martin Commercial Properties team, and focuses on Industrial and Investment Advisory.

These were the questions they cover in this conversation: 
With industrial vacancy rates holding steady, what factors are driving demand in the market, and how do you see this trend evolving in 2025?

How are companies in the industrial sector adapting to supply chain challenges, and what role does location selection play in mitigating these risks?

With major investments from companies like GM, Neogen, and Gestamp, how do these large-scale projects impact industrial property development and investor confidence?

These interviews grow out of a series of three recent reports recently released by the company. You can access them at: https://martincommercial.com/marketinsights/ .

Industrial '24 Market Insights: "INDUSTRIAL ‘24 Market Insights Greater Lansing Area, Michigan | H2 2024"​

The Greater Lansing Area industrial market experienced an increase in the average vacancy rate for leased industrial space, rising from 8.9% in H1 2024 to 11.5% in H2 2024. This increase was primarily driven by significant vacancies in the South Submarket, which saw its vacancy rate jump to 26.5%.  Despite this, the overall market remains strong with healthy demand across most properties, particularly in the West Submarket, which boasts a low vacancy rate of 1.4% and positive net absorption of 63,096 SF. ​

Key developments in the market include Temperpack Technologies leasing 135,000 SF in the West Submarket, General Motors securing a $500 million federal grant for its Lansing Grand River plant, and the ongoing construction of Ultium Cells' 2.8 million SF battery plant.   Additionally, Neogen and Gestamp are making significant investments in new facilities, further indicating strong investor confidence in the region.  The largest owner-user sales in H2 2024 were 65,000 SF at 3366 Remy Dr. for $2.2 million and 55,000 SF at 2200 Olds for $1.1 million. ​

Absorption in the Greater Lansing industrial market totaled -179,614 SF in H2 2024, with the South Submarket experiencing the most significant negative absorption due to large vacancies.  The North Submarket remained relatively stable with minimal changes and no major leases signed.  Overall, the Greater Lansing Area continues to be viewed as a stable and promising market for long-term investment, supported by ongoing developments and strong demand in key submarkets. Investors and occupiers continue to view the Greater Lansing Area as a stable and promising market for long-term investment."

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Michigan Business Beat | Chris Miller, Martin Commercial Properties - Industrial/Investment Advisory

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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/

Cancer and aging are two sides of age-related tumorigenesis.

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

Read about the Aging (Aging-US) Scientific Integrity Process: https://aging-us.com/scientific-integrity

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