Oncotarget

• Immune Side Effects of Liver Cancer Therapy Studied in Latin American Patients

  BUFFALO, NY - May 23, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 19, 2025, titled “Immune-mediated adverse events following atezolizumab and bevacizumab in a multinational Latin American cohort of unresectable hepatocellular carcinoma." The study, led by first authors Leonardo Gomes da Fonseca from Hospital das Clínicas, Universidade de São Paulo, Brazil, and Federico Piñero from Hospital Universitario Austral, Argentina, investigated how patients with advanced liver cancer in Latin America respond to a widely used immunotherapy combination. The researchers found that although a minority of patients developed immune-related side effects, these events did not significantly impact overall survival. Their findings highlight the importance of early recognition and careful management of such side effects in real-world clinical settings. Liver cancer is a leading cause of cancer deaths worldwide, with limited treatment options for patients diagnosed at an advanced stage. Immunotherapy, particularly the combination of atezolizumab and bevacizumab, has become a standard approach. However, these treatments can sometimes trigger the body’s immune system to attack healthy organs, leading to what are called immune-related adverse events, or irAEs. Until now, little data existed on how frequently these events occur in Latin American patients and whether they impact treatment outcomes. The researchers followed 99 patients from Argentina, Brazil, Chile, and Colombia, most of whom had cirrhosis or underlying liver disease. They received atezolizumab and bevacizumab for a median duration of six months. The researchers reported that only 18% of the patients experienced immune-related side effects, most commonly affecting the liver (hepatitis) and thyroid (thyroiditis). Most of these cases were mild or moderate, and half of them resolved completely within a month. Only eight patients needed treatment with steroids to control the immune response. Importantly, the occurrence of immune-related side effects did not affect how long patients survived after starting treatment. The median survival was the same—18.5 months—for both those who experienced irAEs and those who did not. This result suggests that while irAEs require careful management, they may not reduce the overall benefits of immunotherapy. Another significant finding was that patients with higher levels of alpha-fetoprotein (AFP), a protein often elevated in liver cancer, were more likely to experience these side effects. This information could help clinicians identify patients who need closer control during treatment. “Notably, baseline alpha-fetoprotein (AFP) values ≥400 ng/ml were significantly associated with the development of irAEs.” The study also points to key differences between clinical trial results and real-world experiences. While clinical trials report higher rates of side effects, this real-world data showed a lower incidence, possibly due to less intensive monitoring or differences in how side effects are documented in everyday practice. In summary, this study highlights that patients require ongoing vigilance and individualized care when treating liver cancer with immunotherapy. It provides valuable information to healthcare providers in Latin America and other regions with similar patient populations, aiming to improve outcomes while minimizing risks. DOI - https://doi.org/10.18632/oncotarget.28721 Correspondence to - Federico Piñero - fpinerof@cas.austral.edu.ar To learn more about Oncotarget, please visit https://www.oncotarget.com. MEDIA@IMPACTJOURNALS.COM

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• Engineered Proteins Show Promise in Stopping Glioblastoma Invasion

  Scientists have engineered small, targeted proteins that can penetrate brain cancer cells and prevent them from invading healthy tissue, offering a promising new approach to treating glioblastoma multiforme (GBM), one of the deadliest forms of brain cancer. This strategy was developed by researchers at the University of Nevada, Reno, and published recently in Oncotarget. The Challenge of Treating Glioblastoma Multiforme Glioblastoma is an aggressive and fast-growing brain tumor that infiltrates healthy brain tissue, making complete surgical removal nearly impossible. Standard treatments like chemotherapy and radiation can slow its growth but rarely prevent it from returning. One major reason for this invasiveness is a group of enzymes known as matrix metalloproteinases (MMPs), which break down surrounding tissue to allow cancer cells to spread. Among these, MMP-9 plays a particularly important role in driving tumor progression and resisting existing therapies. Attempts to block MMPs using small-molecule drugs have failed in clinical trials due to problems like poor selectivity and harmful side effects. Researchers have been searching for safer, more targeted methods to interfere with these enzymes and limit glioblastoma’s spread. The Study: Engineered Proteins to Inhibit Tumor Invasion In the study called “Effect of TIMPs and their minimally engineered variants in blocking invasion and migration of brain cancer cells,” researchers Elham Taheri and Maryam Raeeszadeh-Sarmazdeh investigated tissue inhibitors of metalloproteinases (TIMPs), which are natural blockers of MMPs, and their engineered modified versions made to work better. Specifically, the team studied TIMP-1, TIMP-3, along with two engineered molecules, mTC1 and mTC3, in laboratory cell models of GBM. Full blog - https://www.oncotarget.org/2025/05/21/engineered-proteins-show-promise-in-stopping-glioblastoma-invasion/ Paper 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 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28691 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, TIMP minimal variants, glioblastoma multiforme (GBM), brain cancer, MMP inhibitors 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

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• Combining Radiation and Immunotherapy Shows Promise for Bladder Cancer

  BUFFALO, NY - May 21, 2025 – A new #review was #published in Volume 16 of Oncotarget on May 19, 2025, titled “Advancements in bladder cancer treatment: The synergy of radiation and immunotherapy." Researchers from the University of California, Irvine, led by Nazmul Hasan, reviewed recent clinical and scientific advances in combining radiation therapy with immunotherapy for bladder cancer. The article summarizes growing evidence that this combined approach may strengthen the immune response and improve long-term disease control. This strategy is especially important for patients who are not candidates for surgery or who respond poorly to conventional treatments. Bladder cancer is a serious and frequent condition, particularly affecting older men. Traditional treatments—surgery, chemotherapy, and radiation—can be effective, but they often fail to prevent cancer reappearance in advanced cases. The review explores how combining radiation and immunotherapy could improve outcomes by helping the immune system detect and destroy cancer cells more effectively. Radiation therapy destroys cancer cells and triggers the release of tumor signals that attract immune cells. Immunotherapy, including drugs like pembrolizumab and nivolumab, helps the immune system work better by blocking proteins that allow cancer to evade detection. Used together, these treatments may produce a stronger, more widespread anti-tumor effect, even at distant sites not directly targeted by radiation. The review discusses several clinical trials that support this approach. One phase II study reported that combining radiation with the immunotherapy drug durvalumab led to promising survival rates and manageable side effects. Another trial in Australia tested pembrolizumab with radiation and chemotherapy, resulting in high tumor control and extended patient survival. However, the review also points out that other trials showed serious side effects when high doses or multiple immunotherapy drugs were used at once. "Joshi et al. performed a phase II study to determine the safety and efficacy of combining radiation therapy with durvalumab, a PD-L1 inhibitor, in patients who were ineligible for surgery or cisplatin-based chemotherapy." While the combination approach is promising, the authors emphasize that more research is needed to refine this treatment strategy. One major challenge is determining which patients are most likely to benefit. Future studies should focus on identifying reliable biomarkers, such as tumor mutation burden or immune activity, to guide personalized treatment plans. This review highlights the potential of combining radiation and immunotherapy to improve outcomes for bladder cancer patients. With continued research and careful treatment design, this approach could offer new treatment options for those facing aggressive or hard-to-treat forms of the disease. DOI - https://doi.org/10.18632/oncotarget.28723 Correspondence to - Nazmul Hasan - nhasan1@hs.uci.edu Video short - https://www.youtube.com/watch?v=AxrZhIUXrOQ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28723 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, bladder cancer, immunotherapy, radiation, microenvironment, abscopal 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

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• New Ultra-Sensitive DNA Blood Test for Detecting Residual Cancer in B-cell Lymphoma Patients

  BUFFALO, NY – May 19, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 9, 2025, titled “Analytical validation of a circulating tumor DNA assay using PhasED-Seq technology for detecting residual disease in B-cell malignancies.” In this study, a team from Foresight Diagnostics led by first author Nina Klimova and corresponding author Laura Hyland validated a new DNA-based blood test designed to detect minimal residual disease (MRD) in patients with B-cell cancers. This assay uses a highly sensitive method called Phased Variant Enrichment and Detection Sequencing (PhasED-Seq) to find tiny fragments of tumor DNA in the blood. Its ultra-sensitive detection capabilities offer a powerful tool for early cancer detection, monitoring treatment response, and predicting cancer reappearance. B-cell lymphomas, such as diffuse large B-cell lymphoma (DLBCL), are among the most prevalent blood cancers. Although many patients respond to initial treatment, up to 40% relapse. Standard monitoring methods such as imaging scans often miss low levels of cancer cells, creating a need for more precise tools. This study introduces a non-invasive blood test that improves the detection of MRD, a critical factor in guiding follow-up care and early intervention. The test works by tracking unique groups of mutations known as phased variants in tumor DNA. These mutations are more specific to cancer and allow for highly accurate identification of tumor fragments in the bloodstream. The PhasED-Seq-based MRD assay was tested on three types of samples. First, blood plasma from healthy individuals was used to confirm the test does not give false positives. Second, researchers created controlled samples by mixing tumor DNA from lymphoma patients with healthy DNA to measure how sensitive and precise the test is. Finally, blood samples from patients with B-cell lymphoma were used to compare the new test to an existing method. Across all sample types, the PhasED-Seq-based MRD assay demonstrated exceptional performance—capable of detecting fewer than one cancer DNA molecule per million normal DNA fragments. It also demonstrated a very low false positive rate and over 96% reproducibility across different laboratory conditions. Compared to an existing method, the new PhasED-Seq assay showed more than 90% agreement in positive results and nearly 78% agreement in negative results. In cases where the tests disagreed, the new method aligned more closely with actual clinical outcomes, including whether patients relapsed or stayed in remission. “The background error rate of the PhasED-Seq-based MRD assay was 1.95E-08, or 1.95 mutant molecules in 100 million informative molecules.” The findings support the use of PhasED-Seq-based MRD assays in routine clinical practice. It could be especially useful for identifying patients who need additional treatment even when imaging results appear normal. This aligns with updated clinical guidelines that encourage the use of blood-based DNA tests to supplement traditional scans in lymphoma care. This study offers strong evidence that the PhasED-Seq-based MRD assay is a precise, reliable, and clinically relevant tool. By detecting signs of cancer earlier and more accurately, it may help clinicians tailor treatments to individual patients and improve long-term outcomes in B-cell malignancies. DOI - https://doi.org/10.18632/oncotarget.28719 Correspondence to - Laura Hyland - laura.hyland@foresight-dx.com Video short - https://www.youtube.com/watch?v=8hdh3G5zvlc 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

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• Blood Type A Identified as Potential Breast Cancer Risk Factor

  BUFFALO, NY - May 14, 2025 – A new #review paper was #published in Volume 16 of Oncotarget on May 9, 2025, titled “Relationship between ABO blood group antigens and Rh factor with breast cancer: A systematic review and meta-analysis." A comprehensive study, led by first authors Rahaf Alchazal from Yarmouk University and Khaled J. Zaitoun from Johns Hopkins University School of Medicine and Jordan University of Science and Technology, examined the potential link between blood type and breast cancer. The research team conducted a systematic review and meta-analysis of 29 previously published studies, involving more than 13,000 breast cancer patients and over 717,000 controls. “Researchers searched for studies on breast cancer patients and ABO blood groups across four major databases: PubMed, Scopus, Web of Science, and Google.“ Breast cancer is the most common cancer among women worldwide. Identifying risk factors is vital for early detection and prevention. While many studies have explored lifestyle and genetic causes, this analysis focused on the ABO blood group system. By pooling global data, the researchers found that blood type A was the most common among breast cancer patients and was significantly associated with an 18% increased risk compared to type O. The study did not find a significant association between breast cancer and blood types B, AB, or Rh factor. Although the results do not prove causation, they point to a biological pattern worth further investigation. Blood group antigens are proteins found on the surface of cells, including breast tissue. These molecules may influence how cancer develops and spreads by interacting with the immune system or affecting cell behavior. This meta-analysis is the most extensive review to date on this topic, based on studies conducted across Asia, Europe, Africa, and the Americas. While previous research found unclear conclusions, this large-scale evaluation provides stronger evidence for a possible connection between blood type A and breast cancer risk. Researchers note that regional differences, genetic diversity, and study quality may affect individual results. Nevertheless, the overall trend supports considering blood type A as a potential risk marker. This insight could help shape screening guidelines, encouraging earlier or more frequent checkups for women with this blood type. Further research is needed to understand why blood type A may play a role in cancer development. Future studies may explore genetic mechanisms, immune responses, and other biological pathways. These efforts could lead the way for more personalized cancer prevention and care strategies. DOI - https://doi.org/10.18632/oncotarget.28718 Correspondence to - Khaled J. Zaitoun - kzaitou1@jh.edu Video short - https://www.youtube.com/watch?v=BQFVtreaetI Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28718 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, breast cancer, cancer risk factors, blood group antigens, tumor 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

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