Oncotarget

BUFFALO, NY - May 5, 2025 – Oncotarget, #published by Impact Journals, is proud to #announce its presence as an #exhibitor at the 47th Annual Meeting of the Society for Scholarly Publishing (SSP), taking place May 28–30, 2025, at the Hilton Baltimore in Maryland.

Impact Journals publishes scholarly journals in the biomedical sciences, with a focus on cancer and aging research.

Attendees are invited to stop by Booth #209 to meet members of the Oncotarget team and learn more about the journal’s latest initiatives. This year’s conference theme, “Reimagining the Future of Scholarly Publishing at the Intersection of Value and Values,” highlights critical topics such as artificial intelligence, research ethics, and transparency in science—principles that closely align with Oncotarget's commitment to rigorous peer review and scientific integrity.

We look forward to connecting with SSP attendees to discuss Oncotarget’s mission, explore potential collaborations, and emphasize the role of open science in advancing cancer research and related fields.

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BUFFALO, NY - April 28, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on April 24, 2025, titled “PD-L1 and FOXP3 expression in high-grade squamous intraepithelial lesions of the anogenital region."

Researchers Humberto Carvalho Carneiro, Rodrigo de Andrade Natal, José Vassallo and Fernando Augusto Soares from the Instituto D’Or de Pesquisa e Ensino and Rede D’Or studied early tissue changes caused by human papillomavirus (HPV) in the anal, vulvar, and penile regions. They found that high-grade pre-cancer lesions triggered stronger immune responses and showed higher levels of two immune-related markers, PD-L1 and FOXP3. These findings are important because they help explain how some HPV-related lesions progress to cancer while others heal on their own.

High-risk HPV is known to cause several types of anogenital cancers. Before these cancers appear, the virus often leads to abnormal tissue changes known as high-grade squamous intraepithelial lesions. Many of these lesions disappear without treatment, but some become cancer—especially in people with weakened immune systems. This study explored how immune activity may play a role in this progression.

The researchers examined tissue from 157 patients—95 males and 55 females—with either high-grade or low-grade HPV-related lesions. They found that T-regulatory cells, marked by the FOXP3 protein, were more common in high-grade lesions. These immune cells are known to suppress immune responses, which can allow infected or abnormal cells to grow. The team also found higher expression of PD-L1, a protein that helps cells evade immune detection, particularly in inflammatory immune cells.

"Dense inflammatory infiltrates and high counts of FOXP3+ cells were significantly more frequent in patients with HSILs than in those with LSILsHR (p = 0.04 and 0.02, respectively). HSILs also exhibited higher PD-L1 expression (padj < 0.01 and < 0.01 for the SP142 and 22C3 clones, respectively), based on the Poisson generalized linear model.”

These findings suggest that HPV may begin avoiding the immune system early in infection, even before cancer develops. The combination of high FOXP3 and PD-L1 levels may create a protective environment for infected cells, making them harder for the body to eliminate. This immune evasion may allow the lesions to remain and, over time, become cancerous.

The study also compared patients with and without HIV to assess whether immune health influenced the results. While those with compromised immune systems had more extensive lesions, PD-L1 and FOXP3 expression was also found in patients with healthy immune systems. This evidence shows that immune evasion by HPV can happen regardless of a person’s immune status.

Understanding how PD-L1 and FOXP3 function in early HPV-related lesions may help clinicians predict which lesions are more likely to become cancer. These insights could lead to new strategies for monitoring, treating, or preventing HPV-related precancerous lesions and cancer in the anogenital region. The study highlights how early immune system changes can play a key role in the development of HPV-related cancers.

DOI - https://doi.org/10.18632/oncotarget.28715

Correspondence to - Humberto Carvalho Carneiro - [email protected]

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A new study from the Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine, published in Oncotarget, reveals that the gene p53, long known as the “guardian of the genome,” may be even more powerful than previously thought. By studying it in non-cancerous human cells, researchers discovered how p53 stops risky cell growth and uncovered two new potential targets for cancer therapy.

Understanding p53: The Genome’s Guardian Against Cancer

The p53 gene is one of the most important natural defenses our body has against cancer. When functioning properly, p53 detects damage in a cell’s DNA and either stops the cell from dividing or pushes it to self-destruct. This process helps prevent potentially dangerous mutations from spreading. However, many cancers find ways to silence or mutate p53, allowing uncontrolled growth and resistance to treatments.

Studying p53 in a clear and accurate way has long been a challenge. Most cancer cell models used in research already carry numerous genetic mutations, which can mask or alter how p53 truly functions. To fully understand this vital tumor-suppressing gene, scientists needed a model that closely resembled healthy, genetically stable human cells—yet could still be maintained and studied over time in the laboratory.

The Study: Exploring p53 in Normal and Cancer Cell Models

Researchers Jessica J. Miciak, Lucy Petrova, Rhythm Sajwan, Aditya Pandya, Mikayla Deckard, Andrew J. Munoz, and Fred Bunz explored p53 activity using a uniquely suitable cell line: hTERT-RPE1. These non-cancerous human cells are immortalized using telomerase, meaning they continue dividing like cancer cells, but without the chaotic mutations seen in tumors. This makes them an excellent model for studying how p53 operates in near-normal conditions.

Full blog - https://www.oncotarget.org/2025/04/22/new-insights-into-p53-a-powerful-genes-role-in-cancer-therapy/

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

Correspondence to - Fred Bunz - [email protected]

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

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Keywords - cancer, p53, ionizing radiation, immortalized cells, ALDH3A1, NECTIN4

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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BUFFALO, NY - April 15, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on April 4, 2025, titled “Association between two single nucleotide polymorphisms of the Prostaglandin-Endoperoxide Synthase 1 and 2 genes and cell proliferative prostatic diseases in Lebanon."

The team of researchers led by first author Brock J. Sheehan and corresponding author Ruhul H. Kuddus, from Utah Valley University, discovered that a specific genetic variation in the PTGS2 gene is associated with a higher risk of benign prostate hyperplasia (BPH), a common condition in aging men. The study, which focused on Lebanese men, suggests that the C allele of the -765 G>C polymorphism in the PTGS2 gene may increase risk to this non-cancerous but problematic prostate condition. This finding could help identify men at greater risk earlier and lead to better treatment choices.

Benign prostate hyperplasia and prostate cancer are two common conditions that involve abnormal cell growth in the prostate gland. While prostate cancer is malignant and potentially life-threatening, BPH is a non-cancerous enlargement that can still significantly affect quality of life. Both conditions are widespread in older men, with BPH affecting over 70% of men above 60. Researchers have long suspected that inflammation-related genes may play a role in their development. In this study, the focus was to study PTGS1 and PTGS2, genes that help produce enzymes involved in inflammation.

Using DNA samples from 168 Lebanese men, including 61 with prostate cancer, 51 with BPH, and 56 healthy controls, the researchers analyzed two common gene variants. They found no link between the PTGS1 variant and either condition. However, the PTGS2 variant showed a strong association with BPH. Men carrying the C version of this gene were more than twice as likely to have BPH compared to those without it. While a similar trend was observed in men with prostate cancer, the results were less conclusive.

"The C allele of SNP-765G>C of the PTGS2 gene was significantly associated with an increased risk of BPH (OR = 2.30, p-value = 0.01)."

This is the first study to report a genetic link between the C allele of the -765 G>C polymorphism in the PTGS2 gene and BPH in Lebanese men. It builds on earlier findings that associated this gene variant with various cancers, including prostate, colon, and stomach cancers. Although based on a relatively small and specific population, the study offers new insight that could help improve genetic screening and guide prevention strategies.

The research also points to the potential benefits of COX-2 inhibitors—drugs already used to treat prostate conditions—which may be more effective for men with certain PTGS2 gene types. Further studies in larger and more diverse groups are needed to confirm these results and explore how this gene variant influences prostate disease. In the future, simple genetic tests could help identify men at higher risk before symptoms appear, allowing for earlier and more personalized care.

Continue reading: DOI: https://doi.org/10.18632/oncotarget.28710

Correspondence to: Ruhul H. Kuddus — [email protected]

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BUFFALO, NY - April 11, 2025 – A new research perspective was published in Oncotarget, Volume 16, on April 4, 2025, titled “GSK3β activation is a key driver of resistance to Raf inhibition in BRAF mutant melanoma cells."

In this work, first author Diana Crisan and corresponding author Abhijit Basu from the University Hospital Ulm led a team that presents experimental evidence pointing to the protein GSK3β as a key contributor to drug resistance in melanoma. Their findings suggest that GSK3β becomes increasingly active in cancer cells during treatment, helping them survive and adapt despite ongoing therapy with BRAF inhibitors.

Melanoma is a type of skin cancer in which nearly half of patients have mutations in the BRAF gene that accelerate tumor growth. While treatments targeting BRAF, known as BRAF inhibitors, initially work well, tumors often find ways to fight back. This research perspective explores how GSK3β, a protein involved in metabolism and cell survival, becomes more active in melanoma cells that develop resistance to BRAF inhibitors.

Researchers treated melanoma cells with a common BRAF mutation using Dabrafenib, a widely used BRAF inhibitor. Over time, the cancer cells developed resistance and showed a marked increase in GSK3β levels. This pattern was confirmed across multiple melanoma cell models, suggesting that the finding is consistent and reliable.

Importantly, the researchers observed that treating resistant cancer cells with a GSK3β inhibitor significantly reduced their growth. This result suggests that blocking this protein could restore sensitivity to treatment, highlighting GSK3β as a promising therapeutic target and supporting the idea of combining GSK3β inhibitors with existing melanoma therapies.

“Remarkably, treatment of BRAFi-resistant melanoma cells with the GSK3 inhibitor LY2090314 for three weeks could overcome resistance and significantly decreased melanoma cell growth, confirming the causal role of GSK3 activation for BRAFi resistance development.”

The research perspective adds to ongoing efforts to understand and overcome melanoma drug resistance. It shows that resistance is not driven only by genetic mutations but may also involve adaptive changes in the cell’s internal signaling and survival mechanisms. By identifying GSK3β as a potential contributor, the authors offer a new direction for improving the durability of targeted treatments in melanoma.

As research continues, GSK3β may be a critical factor in the long-term success of melanoma therapy, particularly for patients who have stopped responding to standard BRAF-targeted drugs.

Continue reading: DOI: https://doi.org/10.18632/oncotarget.28711

Correspondence to: Abhijit Basu — [email protected]

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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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Despite decades of research, treatment for osteosarcoma has remained largely unchanged, especially for patients whose cancer spreads or returns. However, a growing body of evidence, summarized in the review “SETDB1 amplification in osteosarcomas: Insights from its role in healthy tissues and other cancer types,” published in Oncotarget, highlights the gene regulator SETDB1 as a potential key player in cancer progression, immune system evasion, and resistance to therapy. Targeting this protein may offer a new direction for developing more effective treatments.

Understanding Osteosarcoma

Osteosarcoma is a rare but aggressive bone cancer that primarily affects teenagers and young adults. While current treatments like surgery and chemotherapy can help some patients, outcomes are much worse for those with relapsed or advanced disease.

One of the reasons osteosarcomas are so difficult to treat is their complex and unstable genetics. Unlike cancers with well-defined mutations, osteosarcomas involve chaotic DNA rearrangements, making it difficult to identify precise drug targets. Adding to the challenge, the immune system often fails to recognize these cancer cells, limiting the success of immunotherapy.

Full blog - https://www.oncotarget.org/2025/04/09/targeting-setdb1-a-new-strategy-for-treating-osteosarcoma/

Paper DOI - https://doi.org/10.18632/oncotarget.28688

Correspondence to - Antonin Marchais - [email protected], and Maria Eugenia Marques Da Costa - [email protected]

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Keywords - cancer, SETDB1, cancer epigenetics, tumor immunogenicity, mesenchymal differentiation in osteosarcoma

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.

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BUFFALO, NY - April 8, 2025 – A new #editorial was #published in Oncotarget, Volume 16, on April 4, 2025, titled “Deep learning-based uncertainty quantification for quality assurance in hepatobiliary imaging-based techniques."

Dr. Yashbir Singh from Mayo Clinic and his colleagues discussed how artificial intelligence (AI) can improve liver imaging by recognizing when it might be wrong. This approach, called “uncertainty quantification,” helps clinicians better detect liver cancer and other diseases by pointing out areas in medical scans that need a second look. The authors explain how these AI tools could make imaging results more accurate and reliable, which is especially important when diagnosing serious conditions like liver tumors.

Liver and bile duct imaging is difficult because of the organ’s complex structure and differences in image quality. Even skilled radiologists can struggle to identify small or hidden tumors, especially in patients with liver damage or scarring. The editorial explains how new AI models not only read medical images but also measure their own confidence. When the AI system is unsure, it can alert clinicians to take a closer look. This extra layer of information can reduce missed diagnoses and improve early detection of liver cancer.

One of the most advanced tools described in the editorial is called AHUNet (Anisotropic Hybrid Network). This AI model works with both 2D and 3D images and can highlight which parts of a scan it is most confident about. It performed well when measuring the entire liver and showed how its confidence dropped when scanning smaller or multiple lesions. This feature helps clinicians know when more testing or review is needed.

The authors also looked at other AI models used in liver imaging. Some tools were able to analyze liver fat using ultrasound images and give clinicians both a result and a confidence score. Others improved the speed and accuracy of liver magnetic resonance imaging (MRI) scans, helping to create clear images in less time. These advancements could help hospitals work faster and provide better care.

The editorial highlights how this technology can be especially helpful in smaller clinics. If they do not have liver specialists, they could still use AI systems that flag uncertain results and send them to larger centers for review. Such an approach could improve care in rural or less-resourced areas.

“Radiology departments should develop standardized reporting templates that incorporate uncertainty metrics alongside traditional imaging findings.”

By using AI tools that know when to second-guess themselves, clinicians may soon have more reliable methods for detecting liver cancer and monitoring liver disease. The authors suggest that uncertainty-aware AI may soon become a vital part of everyday medical imaging, supporting faster and more accurate decisions in liver disease care.

DOI: https://doi.org/10.18632/oncotarget.28709

Correspondence to: Yashbir Singh — [email protected]

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Keywords: cancer, deep learning, uncertainty quantification, radiology, hepatobiliary imaging

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BUFFALO, NY - April 4, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on March 27, 2025, titled “Imipridones ONC201/ONC206 + RT/TMZ triple (IRT) therapy reduces intracranial tumor burden, prolongs survival in orthotopic IDH-WT GBM mouse model, and suppresses MGMT."

Researchers from Brown University, led by first author Lanlan Zhou and corresponding author Wafik S. El-Deiry, have shown that combining a new class of drugs called imipridones with standard glioblastoma treatments significantly improves outcomes in mice. The study tested ONC201 and its analog ONC206 in combination with radiation therapy and the chemotherapy drug temozolomide (TMZ), a regimen referred to as IRT. This triple therapy slowed tumor growth and extended survival in a mouse model of glioblastoma, offering a potential new strategy for one of the most aggressive and treatment-resistant brain cancers.

Glioblastoma is a fast-growing brain tumor with a poor prognosis and limited treatment options. Standard care typically includes surgery, radiation, and TMZ, but most patients still face a short life expectancy. While ONC201 and ONC206 are currently being studied in clinical trials as single agents, there has been limited information on how they interact with standard therapies. This study is the first to show that both drugs work synergistically with radiation and TMZ, strengthening their overall effects.

The results showed that in both laboratory-grown tumor cells and mice, the triple therapy significantly slowed cancer cell growth, reduced tumor size, and prolonged survival compared to using any single or double treatment. Mice treated with IRT lived an average of 123 days, with some surviving more than 200 days—far longer than the 44 to 103 days observed with other treatment combinations. In addition to directly killing tumor cells, ONC201 and ONC206 lowered the expression of MGMT, a protein that helps tumors resist chemotherapy, making the treatment more effective.

The researchers also found that the triple therapy reshaped the tumor environment. It decreased levels of harmful molecules that promote tumor growth and immune evasion while increasing signals that activate the immune system. This dual action—directly attacking tumors and boosting immune responses—adds to the potential impact of this treatment approach.

“Overall, our preclinical findings support further exploration of the ONC201 and ONC206 IRT regimen as a potential treatment for GBM and diffuse gliomas with H3K27M mutations.”

While these findings are based on preclinical mouse models, they offer strong support for advancing this triple therapy to clinical trials. ONC201 and ONC206 are promising due to their ability to cross the blood-brain barrier and enhance the effects of standard treatment. This combination could lead to more effective therapies for glioblastoma and other hard-to-treat brain tumors.

DOI - https://doi.org/10.18632/oncotarget.28707

Correspondence to - Wafik S. El-Deiry - [email protected]

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BUFFALO, NY - March 31, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on March 21, 2025, titled “FGR Src family kinase causes signaling and phenotypic shift mimicking retinoic acid-induced differentiation of leukemic cells."

A research team led by first author Noor Kazim and corresponding author Andrew Yen from Cornell University discovered that the FGR protein—traditionally considered a cancer-promoting molecule—can instead trigger leukemia cells to mature. This effect mirrors the response usually induced by retinoic acid (RA); a compound derived from vitamin A that is widely used in cancer therapy. Their finding presents a potential new path for therapies targeting acute myeloid leukemia (AML) and related cancers.

Acute myeloid leukemia is often treated using RA-based therapies that force immature white blood cells to mature, slowing their rapid growth. Retinoic acid works through complex signaling and gene regulation involving a group of proteins that orchestrate this transformation. In this study, the team used HL-60 cells, a model for human leukemia, and engineered them to express FGR. Surprisingly, the presence of FGR alone was enough to make these cells mature in a way almost identical to what happens with RA treatment. They began producing well-known markers of maturation such as CD38 and CD11b, generated reactive oxygen species (ROS), and expressed the inhibitor of the cell cycle, p27, all signs that the cells had shifted from a cancer-like, fast-dividing state to a more specialized, mature form.

Further analysis revealed that FGR activated a group of proteins known as the "signalsome," which helps trigger the changes needed for cells to differentiate. This same group is typically activated by RA.

“Notably, FGR induces the expression of genes targeted by RAR/RXR, such as cd38 and blr1, even without RA."

To test its potential use in treatment-resistant leukemias, the researchers introduced FGR into RA-resistant HL-60 cells. In these, FGR did not cause the same maturation process, which suggests that there are other problems with cell signaling that stop both the RA and FGR pathways. This result highlights the complexity of resistance mechanisms and the need for additional research.

These findings challenge the traditional view of FGR as strictly a cancer-driving protein. Instead, in this specific context, it appears to initiate anti-cancer behavior. That a single protein can reproduce the effects of a complex therapeutic compound like RA is both surprising and promising. If future research confirms this study's results in more advanced models, FGR could become a new tool for developing therapies for AML and potentially other blood cancers.

DOI - https://doi.org/10.18632/oncotarget.28705

Correspondence to - Andrew Yen - [email protected]

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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.

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BUFFALO, NY - April 2, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on March 21, 2025, titled “NSD2-epigenomic reprogramming and maintenance of plasma cell phenotype in t(4;14) myeloma."

Researchers Andrea Gunnell, Scott T. Kimber, Richard Houlston, and Martin Kaiser from The Institute of Cancer Research, London, studied how a gene called NSD2 affects the behavior of multiple myeloma (MM) cells. Their findings reveal that NSD2 plays a key role in helping cancer cells retain their identity as plasma cells—white blood cells that normally help the immune system fight infections. This discovery could shape future treatment strategies for patients with a high-risk form of MM known as t(4;14) myeloma.

Multiple myeloma is a type of blood cancer that begins in plasma cells found in the bone marrow. About 20% of patients have a genetic change called t(4;14), which makes the NSD2 gene highly active. The research team compared two types of myeloma cells: one with high NSD2 activity and one where NSD2 was turned off. They found that when NSD2 is active, it changes how DNA is folded and how genes are switched on or off, especially genes that help the cells act like plasma cells. When NSD2 was turned off, important markers like CD38 were reduced, and other genes normally silent in plasma cells were activated.

The study indicated that NSD2 does not directly affect the main genes responsible for plasma cell creation. Instead, it influences many other genes that help maintain the cancer cell’s identity, which contributes to cancer growth and survival.

The researchers also observed physical changes in the cancer cells. Cells with active NSD2 looked and behaved more like typical plasma cells, while cells without NSD2 appeared more immature and lost important surface markers. These changes were linked to differences in how the DNA was organized inside the cells.

These findings are especially important as new drugs are being developed to block NSD2. The study suggests that turning off NSD2 could change how MM cells respond to existing treatments. For example, if NSD2 is blocked and CD38 levels drop, the change might affect therapies that target CD38. However, the rise of other immune-related genes might make certain immunotherapies more effective.

“Identifying the biological consequences of NSD2 over-expression in MM is not only relevant to informing new therapeutic interventions through indirect targeting of downstream effectors, but also to anticipate possible consequences of targeting NSD2 directly.”

In summary, this study shows how NSD2 helps myeloma cells keep their cancerous identity by reorganizing the DNA and influencing gene activity. Understanding this role could help researchers design better treatment approaches and possibly overcome resistance to current therapies in t(4;14) myeloma.

DOI - https://doi.org/10.18632/oncotarget.28706

Correspondence to - Andrea Gunnell - [email protected]

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