Oncotarget

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

BUFFALO, NY - October 1, 2025 – Oncotarget is proud to announce that its Editor-in-Chief, Wafik S. El-Deiry, MD, PhD, FACP, will chair the WIN Symposium as the Oncology Track of the Advancing Precision Medicine (APM) Annual Conference held October 3–4, 2025, at the Pennsylvania Convention Center in Philadelphia. The WIN Consortium annual symposium featured as the Oncology Track of the APM Annual Conference 2025 unites global leaders in oncology, translational science, and precision medicine. This year’s program features keynote lectures, multi-track sessions– WIN Symposium, Multi-Omics Integration and Precision Medicine Outside of Oncology– and networking opportunities designed to accelerate the translation of research into clinical practice. Highlights include: --A keynote at opening of the WIN Symposium in Philadelphia by William G. Kaelin, Jr., MD — 2019 Nobel Laureate. --Other luminaries in Oncology are speaking, including AACR President Lillian Siu, MD and AACR President-Elect Keith Flaherty, MD along with internationally recognized leaders in precision oncology. --A world-class precision oncology molecular tumor board and oral presentations from the most competitive abstracts are part of the program. --Multi-omics and disease-specific tracks spanning oncology, neurology, cardiovascular disease, rare disease, and infectious disease. --Opportunities for collaboration among scientists, clinicians, industry innovators, and policymakers. Registration is still open. Attendance is free for students, academic/government/non-profit participants, healthcare providers, and investors. The event provides CME credits. For full program details, visit the APM Annual Conference website. About WIN Consortium: WIN Consortium is a non-profit association headquartered in France. WIN was the first consortium that assembled all stakeholders of cancer care, from academia, industry, and patient advocates to work together across the globe. The WIN network assembles 34 world-class academic medical centers, industries, research organizations and patient advocates spanning 18 countries and 5 continents, aligned to launch trials to bolster Precision Oncology across the world. It was also the first organization to launch a N-of-One study using transcriptomics in addition to genomics to inform therapeutic choice in the WINTHER study. WIN is the organizer of the WIN symposia in Precision Oncology. 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

Explore the challenges of metastatic colorectal cancer and how precision oncology is reshaping treatment. A case study of a 62-year-old man showcases a personalized care plan developed after standard therapies were exhausted. The discussion dives into genomic profiling, revealing critical mutations that influenced tailored drug combinations. Although the patient faced a tragic outcome, the insights underscore the importance of advanced testing and equitable access to innovative therapies for improved patient care.

Discover how the loss of the Trp53 gene significantly impacts ovarian cancer progression. Researchers reveal that deleting this key tumor suppressor results in more aggressive tumors and weakened immune responses. The study highlights why some high-grade serous ovarian carcinomas resist immunotherapy, illustrating that fewer active T cells and reduced pro-inflammatory signaling allow tumors to evade immune detection. The findings open new avenues for enhancing treatment strategies in this deadly cancer type.

A groundbreaking study reveals unexpected successes with immunotherapy in pancreatic cancer, challenging the norm that this treatment rarely works. It highlights rare cases of patients with positive responses, prompting a reevaluation of tumor biology and immune interactions. The research underscores the potential for personalized treatment approaches in a disease typically known for its poor prognosis and limited options.

Researchers are making breakthroughs in fighting rhabdomyosarcoma, a common pediatric cancer, by targeting the protein quality control system in cancer cells. Disruption of this system slows tumor growth in mice, offering hope for improving treatments for high-risk cases that resist standard therapies. The study indicates that new strategies, like using the compound MAL3-101, could enhance outcomes for young patients facing aggressive cancers. This innovative approach could reshape how we understand and treat childhood cancer.

Aiden Deacon, a cancer biology PhD student at the University of Colorado Anschutz, shares insights from his research on the R-spondin family genes and their role in metastatic prostate cancer. He discusses how alterations in RSPO2 are linked to poorer survival rates in patients. The conversation touches on the gene's impact on epithelial-mesenchymal transition pathways, suggesting potential for targeted therapies. Deacon emphasizes the importance of understanding these regulatory mechanisms for advancing cancer treatment.

Discover the fascinating case of a patient with advanced non-small cell lung cancer who found success with amivantamab monotherapy, despite struggling with rare EGFR mutations. This discussion highlights the unique challenges of treating EGFR variants and the potential breakthroughs in targeting CNS involvement. Listeners will learn about the implications of this case for future research and treatment strategies in oncology, especially for patients facing limited options.

Exploring an innovative combo therapy, researchers reveal how aramchol enhances the effectiveness of regorafenib against gastrointestinal tumors. This intriguing study showcases its potential to personalize cancer treatment by targeting specific genetic variants. Remarkably, the combination not only kills cancer cells more effectively but also demonstrates reduced side effects in animal models. Discover how this strategy could reshape liver and colorectal cancer therapies while offering hope for less toxic options.