Oncotarget

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare blood cancer that primarily affects older adults. One of the key challenges in diagnosing and treating BPDCN is that it closely resembles other forms of leukemia in both appearance and behavior. This overlap often leads to delays or uncertainty in diagnosis, especially since currently there is no single, reliable marker that clearly distinguishes BPDCN from related diseases. To address this issue, researchers from the City of Hope Comprehensive Cancer Center investigated the genetic profile of BPDCN. Their study, titled “Genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A single institution experience,” was published in Oncotarget (Volume 16). Full blog - https://www.oncotarget.org/2025/10/22/genetic-study-identifies-potential-diagnostic-marker-for-rare-blood-cancer-bpdcn/ Paper DOI - https://doi.org/10.18632/oncotarget.28742 Correspondence to - Michelle Afkhami - mafkhami@coh.org Abstract video - https://www.youtube.com/watch?v=wUjr3uU3onI Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28742 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Next-generation sequencing (NGS), CCDC50 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 Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY – October 20, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on October 16, 2025, titled “Widespread folate receptor expression in pediatric and adolescent solid tumors – opportunity for intraoperative visualization with the novel fluorescent agent pafolacianine.” In this study, led by first author Ashley C. Dodd from Ann & Robert H. Lurie Children’s Hospital and corresponding author Timothy B. Lautz from the same institution and Northwestern University Feinberg School of Medicine, researchers discovered that folate receptor beta (FRβ) is widely expressed in various pediatric and adolescent solid tumors. This finding highlights FRβ as a promising target for improving the accuracy of tumor surgery using a fluorescent imaging agent known as pafolacianine. Pediatric cancers are often challenging to remove completely during surgery, particularly when tumors spread or form small metastases. Fluorescence-guided surgery is a method that helps surgeons better identify tumors during operations using special imaging dyes. However, commonly used dyes such as indocyanine green are not tumor-specific and rely on general features of blood vessel permeability, limiting their precision. In this study, researchers investigated the potential of pafolacianine, a next-generation dye that targets folate receptors, for pediatric use. Folate receptors are proteins commonly found on the surface of cancer cells. Pafolacianine is already FDA-approved for adults with ovarian and lung cancers due to its ability to bind these receptors and highlight tumors during surgery. The research team analyzed tissue samples from 13 young patients diagnosed with various cancers, including Wilms tumor, osteosarcoma, synovial sarcoma, rhabdomyosarcoma, Ewing sarcoma, and neuroblastoma. The results showed that FRα was predominantly absent, whereas FRβ was present in 100% of the tumor samples. Notably, FRβ appeared both on the tumor cells and in the surrounding tumor microenvironment but showed little to no expression in normal tissue, making it an excellent candidate for targeted imaging. “In this study, we performed immunohistochemistry staining on slides obtained from a range of pediatric patients with solid tumors.” This consistent expression of FRβ in pediatric tumors is a significant and novel finding. Earlier studies primarily linked FRβ to immune cells called tumor-associated macrophages. This study reveals that FRβ is also expressed directly on tumor tissue, which could help surgeons better distinguish cancer from healthy tissue during procedures. Based on these results, the team has launched a clinical trial to evaluate pafolacianine in children undergoing surgery for metastatic lung tumors. If successful, this method could make pediatric cancer surgery safer and more effective. Overall, this study suggests that targeting FRβ with pafolacianine could serve as a tumor-agnostic imaging strategy, applicable across a wide range of pediatric solid tumors. This represents a potential advancement in real-time surgical imaging and a step forward in pediatric cancer care. DOI - https://doi.org/10.18632/oncotarget.28772 Correspondence to - Timothy B. Lautz - TLautz@luriechildrens.org Abstract video - https://www.youtube.com/watch?v=0its0QkOcwM Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ 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 Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY – October 14, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on October 13, 2025, titled “Treatment of glioblastoma with tumor-specific amplitude-modulated radiofrequency electromagnetic fields.” The study, led by Hugo Jimenez from Wayne State University School of Medicine, Karmanos Cancer Institute, introduces a novel treatment approach for glioblastoma, an aggressive and often treatment-resistant brain cancer. The findings open a new potential path for patients who currently have limited therapeutic options. The approach uses a device developed by TheraBionic that delivers extremely low levels of radiofrequency electromagnetic fields, tuned to frequencies associated with glioblastoma. In laboratory experiments, this therapy significantly slowed the growth of multiple glioblastoma cell lines. It was especially effective against tumor stem cells, which are known to resist standard treatments and drive cancer reappearance. Researchers also found that the treatment’s effects depend on a calcium channel in tumor cells known as Cav3.2 (CACNA1H). When this channel was blocked, the therapy lost its effectiveness, highlighting the channel’s essential role in how tumor cells respond to the signal. The therapy also disrupted the process of cell division by interfering with the mitotic spindle, a structure critical for cell replication. This disruption was associated with changes in the expression of genes that regulate cell division, particularly those involved in the “Mitotic Roles of Polo-Like Kinase” pathway. These effects were specific to tumor-targeted frequencies, as non-matching signals had no measurable impact. The study also includes data from two patients with difficult-to-treat brain tumors who received the therapy through compassionate use. One patient with recurrent glioblastoma showed signs of clinical and radiographic improvement after one month of treatment. Another patient with oligodendroglioma tolerated the therapy well and had stable disease during follow-up imaging. Neither patient experienced serious side effects, further supporting the safety of the therapy. “There was evidence of clinical and radiological benefit in a 38-year-old patient with recurrent GB and evidence of safety and feasibility in a 47-year-old patient with oligodendroglioma.” This is the first study to demonstrate that tumor-specific radiofrequency therapy can suppress both tumor growth and cancer stem cells in glioblastoma. Similar results had previously been observed in liver and breast cancers. These findings contribute to the growing body of evidence supporting a new class of systemic, non-toxic cancer therapies. Further clinical trials will be crucial to confirm these results and fully assess the potential of this approach for treating brain cancer. DOI - https://doi.org/10.18632/oncotarget.28770 Correspondence to - Hugo Jimenez - hugo.jimenez@wayne.edu Abstract video - https://www.youtube.com/watch?v=uxYnWcNKYfg Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28770 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, oncology, amplitude-modulated radiofrequency electromagnetic fields, glioblastoma, TheraBionic, CACNA1H, Cav3.2 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 Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Lung cancer remains one of the leading causes of cancer-related deaths worldwide. Although precision medicine has improved outcomes for many patients, certain rare genetic mutations are still poorly understood, particularly in regions with limited access to genomic testing. Such mutations involve the HER2 gene, better known for its role in breast cancer but also implicated in a small subset of lung cancers. HER2 mutations are found in approximately 2–4% of non-small cell lung cancer (NSCLC) cases and create unique challenges. These tumors can vary significantly in how they appear under a microscope and in how they respond to treatment. Adding to the complexity, most diagnostic and treatment guidelines are based on research from high-income countries, which may not reflect the genetic diversity seen in other parts of the world. To help close this knowledge gap, researchers in Northeastern Brazil conducted one of the first detailed investigations into HER2-mutated NSCLC in Latin America. Their study, recently published in Volume 16 of Oncotarget, reveals a complex and often overlooked form of the disease, highlighting the need for broader access to targeted therapies in underserved populations. Full blog - https://www.oncotarget.org/2025/10/08/new-insights-into-her2-mutated-non-small-cell-lung-cancer-in-brazil/ Paper DOI - https://doi.org/10.18632/oncotarget.28737 Correspondence to - Fabio Tavora - stellacpak@outlook.com Abstract video - https://www.youtube.com/watch?v=hr5R9iDBFFI Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28737 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, HER2 mutation, NSCLC, lung cancer, targeted therapy, genomic profiling 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 Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY – October 8, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on October 6, 2025, titled “ACTM-838, a novel systemically delivered bacterial immunotherapy that enriches in solid tumors and delivers IL-15/IL-15Rα and STING payloads to engage innate and adaptive immunity in the TME and enable a durable anti-tumor immune response.” In this study, led by first author Kyle R. Cron and corresponding author Akshata R. Udyavar, researchers from Actym Therapeutics developed a new form of bacterial immunotherapy called ACTM-838. This treatment safely delivers immune-activating proteins directly to solid tumors. The approach may offer a new option for cancer patients whose solid tumors are resistant to current immunotherapies. Solid tumors often suppress the immune system, making it difficult for treatments like immune checkpoint inhibitors to work effectively. ACTM-838 was designed to overcome this challenge by targeting phagocytic immune cells within the tumor microenvironment (TME). Once inside the tumor, the therapy delivers two immune-stimulating components: IL-15/IL-15Rα and a modified version of STING. Both are known to activate the body’s innate and adaptive immune responses. This combination of immune-stimulating proteins helps shift the TME from immune-suppressive to immune-permissive, enabling the body’s natural defenses to fight the cancer. “STACT is a modular, genetically engineered live attenuated S. Typhimurium bacterial platform that enables tissue-specific localization and cell-targeted delivery of large, multiplexed payloads via systemic administration.” The study highlights how ACTM-838, built on a specially modified strain of Salmonella Typhimurium, safely targets tumors and avoids healthy tissue after intravenous injection. This targeted delivery reduces the risk of side effects while ensuring the immune-boosting agents reach their intended location. Importantly, ACTM-838 also showed significantly reduced inflammatory toxicity compared to its parent bacterial strain, which had previously presented challenges in clinical use. In preclinical tests, ACTM-838 shrank tumors and prevented their recurrence after treatment. Mice that were cured of tumors resisted re-injection with cancer cells, suggesting the development of long-lasting immune memory. The therapy also showed strong synergy with anti-PD1 drugs, a widely used class of cancer treatments, further improving outcomes in both treatment-resistant and responsive tumor models. Researchers also found that ACTM-838 changed the composition of immune cells within the tumor. It increased beneficial cells like cytotoxic T-cells and antigen-presenting macrophages, while reducing suppressive cell types such as regulatory T-cells and exhausted T-cells. These effects were confirmed through genetic analysis and cellular studies, pointing to a broad and coordinated immune response. This study offers proof-of-concept that live bacterial therapy can safely and effectively deliver gene-based immune modulators directly to tumors. With ACTM-838 now being tested in a Phase I clinical trial, the findings offer a new direction for cancer treatment strategies that activate the body’s own immune system, particularly in difficult-to-treat cases where other therapies fail. DOI - https://doi.org/10.18632/oncotarget.28769 Correspondence to - Akshata R. Udyavar - akshata.udyavar@pfizer.com Abstract video - https://www.youtube.com/watch?v=fr5OR3tvC_I Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM