SCD1 Inhibition Strategy Shows Potent Synergy with Regorafenib and Metformin in Tumor Cell Killing

Rare Dual-Mutation GIST Responds to Targeted Therapy, Challenging Established Tumor Biology

BUFFALO, NY – May 6, 2026 – A new #casereport was #published in Volume 17 of Oncotarget on May 4, 2026, titled “Small bowel GIST harboring concurrent KIT exon 9 duplication and SDHC mutation: A case report.” The study was led by first author Cameron B. Speyer from the UCLA David Geffen School of Medicine, and corresponding author Joseph G. Crompton, who holds appointments at both the UCLA David Geffen School of Medicine and the Jonsson Comprehensive Cancer Center. In this report, the authors describe a rare and clinically informative case of a small bowel gastrointestinal stromal tumor (GIST) harboring two genetic alterations that are typically considered mutually exclusive. GISTs are most commonly driven by activating mutations in the KIT or PDGFRA genes, which confer sensitivity to targeted therapies such as imatinib. In contrast, tumors associated with succinate dehydrogenase (SDH) deficiency represent a distinct subgroup that is generally resistant to these treatments. The patient, a 68-year-old man, presented with progressive abdominal pain, bloating, and constipation. Imaging studies revealed a large heterogeneous mass in the lower abdomen measuring up to 18 cm. A biopsy confirmed a spindle cell neoplasm consistent with GIST, with immunohistochemical staining positive for CD117 and DOG1. Genomic analysis identified both a KIT exon 9 duplication (A502_Y503) and a germline SDHC mutation (p.R50C)—a highly unusual combination. Despite the presence of the SDHC mutation, which is typically associated with resistance to therapy, the patient demonstrated a strong response to high-dose imatinib. After six months of neoadjuvant treatment, imaging showed a marked reduction in tumor size and metabolic activity, enabling successful surgical resection. “This case suggests that oncogenic KIT signaling may remain the dominant driver of GIST behavior despite the presence of a germline SDHC mutation and highlights the importance of integrated molecular interpretation in GIST management.” Pathologic examination of the resected tumor revealed significant treatment response, including extensive necrosis and reduced tumor viability. Notably, immunohistochemistry demonstrated retained SDHB expression, indicating preserved SDH complex function despite the identified germline mutation. The case highlights an important clinical insight: not all detected genetic alterations contribute equally to tumor behavior. While SDH-deficient GISTs are typically resistant to imatinib, this tumor behaved in a manner consistent with KIT-driven disease, underscoring the importance of interpreting molecular findings within their clinical and pathological context. Overall, this report emphasizes the need for integrated molecular analysis in cancer diagnosis and treatment. As next-generation sequencing becomes more widely used, clinicians may encounter tumors with multiple coexisting mutations. Determining the dominant oncogenic driver is essential for selecting the most effective therapy and improving patient outcomes. DOI - https://doi.org/10.18632/oncotarget.28863 Correspondence to - Joseph G. Crompton - jcrompton@mednet.ucla.edu Abstract video - https://www.youtube.com/watch?v=eB_QG2vBNCE Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, GIST, KIT duplication, SDHC mutation, genetic testing, case report 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

Mapping the Hidden Structure of Glioma Research: What Are We Missing?

Glioma research has evolved rapidly over the past decade, driven by breakthroughs in molecular biology, imaging technologies, and computational tools. Today, clinicians can classify tumors with far greater precision than ever before, using genetic mutations, epigenetic markers, and advanced diagnostic frameworks. Yet, despite this progress, an important question remains: are we truly capturing the full picture of what shapes patient outcomes? Traditionally, glioma classification has focused on what can be measured in the tumor itself—its histology, molecular profile, and biological behavior. While these factors are undeniably critical, they may not fully explain why patients with similar tumors can experience very different clinical trajectories. Increasingly, researchers are beginning to recognize that broader influences—particularly social and environmental factors—may also play a role. Understanding how these different layers of information connect is becoming an important challenge in neuro-oncology. A review was published in Volume 17 of Oncotarget on March 31, 2026, titled “Bibliometric mapping of glioma classification research through main path, key route, and K-core analyses.” The study was led by first and corresponding author Kayode Ahmed from The University of Texas MD Anderson Cancer Center, in collaboration with Juan E. Núñez-Ríos from Universidad Panamericana. Full blog - https://www.oncotarget.org/2026/05/05/mapping-the-hidden-structure-of-glioma-research-what-are-we-missing/ Paper DOI - https://doi.org/10.18632/oncotarget.28851 Correspondence to - Kayode Ahmed - kmahmed@mdanderson.org Abstract video - https://www.youtube.com/watch?v=v8h2z3eEMFM Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28851 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, glioma research, social network analysis, socio-clinical domains, web of science, networks To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us on social media: 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

Targeted Therapies Drive Long-Term Decline in Multiple Myeloma Mortality in the U.S.

BUFFALO, NY – April 29, 2026 – A new #research paper was #published in Volume 17 of Oncotarget on April 28, 2026, titled “Targeted therapeutics and U.S. population-level mortality trends in multiple myeloma: A SEER-based analysis from 1975 to 2023.” The study was led by first and corresponding author Navkirat Kahlon from the Mass General Cancer Center at Wentworth-Douglass Hospital, in collaboration with researchers from multiple U.S. institutions. In this study, the researchers examined how mortality trends in multiple myeloma have changed in the United States over nearly five decades, using population-level data from the SEER database. Multiple myeloma, a cancer of plasma cells, has historically been associated with poor survival outcomes, but treatment options have evolved dramatically over time. The analysis revealed a clear shift in mortality trends that closely parallels major therapeutic advances. Between 1975 and the mid-1990s, mortality rates steadily increased, reflecting the limited effectiveness of early treatments such as alkylating agents and corticosteroids. A turning point emerged in the 1990s with the introduction of autologous stem cell transplantation, which marked the first meaningful improvement in survival outcomes. Over the following years, the development of targeted therapies—including immunomodulatory drugs and proteasome inhibitors—was associated with a more pronounced decline in mortality. These treatments introduced new mechanisms of action, such as immune modulation and enhanced cancer cell apoptosis, significantly improving disease control. More recent years have seen further progress with the introduction of monoclonal antibodies, maintenance therapies, and combination treatment strategies. Notably, the steepest decline in mortality occurred between 2021 and 2023, coinciding with the clinical adoption of advanced immunotherapies such as CAR T-cell therapies and bispecific antibodies. These treatments have shown the ability to induce deep and durable responses, even in heavily pretreated patients. “Our findings highlight the real-world impact of targeted therapies on population-level outcomes and underscore the urgent need for care models that ensure accessibility, affordability, and long-term sustainability in the era of precision oncology.” Importantly, while these therapeutic advances have improved survival, they have also introduced new challenges. Many patients now require long-term treatment, which can be associated with cumulative toxicities and a significant financial burden. In addition, access to these therapies remains uneven, influenced by geographic, socioeconomic, and healthcare system factors. Overall, this study provides a comprehensive, real-world view of how advances in cancer treatment have translated into measurable improvements in survival at the population level. At the same time, it highlights the need to ensure that these benefits are both sustainable and accessible to all patients as the field continues to evolve. DOI - https://doi.org/10.18632/oncotarget.28877 Correspondence to - Navkirat Kahlon - nkahlon@mgb.org; (ORCID: https://orcid.org/0000-0003-1115-2029) Abstract video - https://www.youtube.com/watch?v=-TNWkG9FyUo 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 on social media: 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

SCD1 Inhibition Strategy Shows Potent Synergy with Regorafenib and Metformin in Tumor Cell Killing

Cancer has long been understood through a variety of biological frameworks, including genetic mutations, dysregulated signaling pathways, and uncontrolled cell proliferation. Yet, these models often capture the visible consequences of disease rather than the deeper metabolic dependencies that sustain tumor survival. Despite major advances in targeted therapies, a central challenge remains: what underlying mechanisms make cancer cells vulnerable to treatment, and how can these vulnerabilities be exploited more effectively? Increasing attention has shifted toward cellular metabolism—particularly lipid regulation and energy-sensing pathways such as AMPK—as critical determinants of tumor behavior. Scientists are now taking a closer look at how metabolism works together with stress responses like autophagy—and how this connection could be used to develop better cancer treatments. A new research paper was published in Volume 17 of Oncotarget, titled “The SCD1 inhibitor aramchol interacts with regorafenib and metformin to kill tumor cells.” The study was led by first author Michael R. Booth and corresponding author Paul Dent from Virginia Commonwealth University, in collaboration with Laurence Booth and Jane L. Roberts from Virginia Commonwealth University and John M. Kirkwood from the University of Pittsburgh Cancer Institute. Full blog - https://www.oncotarget.org/2026/04/21/scd1-inhibition-strategy-shows-potent-synergy-with-regorafenib-and-metformin-in-tumor-cell-killing/ Paper DOI - https://doi.org/10.18632/oncotarget.28861 Correspondence to - Paul Dent - paul.dent@vcuhealth.org Abstract video - https://www.youtube.com/watch?v=lmX_c2e_-HY Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28861 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, macroautophagy, ER stress, aramchol, regorafenib, BID 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

Epigenetic Dysregulation of PDX1 Drives Prostate Cancer Progression

BUFFALO, NY – April 15, 2026 – A new #research paper was #published in Volume 17 of Oncotarget on March 31, 2026, titled “Epigenetic dysregulation and biological function of PDX1 in prostate cancer.” The study was led by first author Tayo A. Adeyika and corresponding author Bernard Kwabi-Addo from Howard University, Washington, DC. The team explored the role of the pancreatic and duodenal homeobox 1 (PDX1) gene in prostate cancer, with a focus on its epigenetic regulation and biological function. Their analysis identified PDX1 as differentially hypermethylated in prostate cancer tissues compared to normal prostate samples, alongside a paradoxical increase in protein expression in tumor tissues. Experiments in prostate cancer cell lines showed that PDX1 overexpression significantly enhanced cell proliferation and migration, while knockdown of PDX1 suppressed these tumor-associated behaviors. These findings point to a clear role for PDX1 in promoting aggressive cancer phenotypes. The work further shows that PDX1 regulates key metabolic, inflammatory, and epithelial–mesenchymal transition (EMT) pathways, including genes such as INSR, IGF1R, TWIST1, and SNAI1. Notably, these effects were more pronounced under high-glucose conditions, suggesting a link between metabolic state and prostate cancer progression. “Overall, our findings suggest that PDX1 plays a tumor-promoting role in human PCa cells by influencing expression of metabolites in insulin, inflammatory, and epithelial-mesenchymal transition (EMT) signaling pathways.” The authors conclude that PDX1 may represent a potential therapeutic target, particularly in the context of metabolic disorders such as obesity and diabetes, which are known to influence prostate cancer risk and progression. Their findings provide new insight into the interplay between epigenetics, metabolism, and tumor biology in prostate cancer. DOI - https://doi.org/10.18632/oncotarget.28854 Correspondence to - Bernard Kwabi-Addo - bkwabi-addo@howard.edu Abstract video - https://www.youtube.com/watch?v=itYVsyXJJoE Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28854 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, PDX1, DNA methylation prostate cancer, shRNA knockdown, over-expression, glucose 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