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Oncotarget
By Oncotarget PodcastScience
Oncotarget episodes
- Immunotherapy Response in Pancreatic Cancer: What a New Study RevealsImmunotherapy is not usually effective against pancreatic cancer (PC), but a new study published in Oncotarget (Volume 16, 2025) highlights rare cases where it did help. These examples, though uncommon, may offer valuable insights for future treatment.Pancreatic Cancer and ImmunotherapyPancreatic cancer is often diagnosed at an advanced stage, which limits treatment options and contributes to its poor prognosis. While chemotherapy remains the standard treatment, it usually offers only modest benefits in terms of survival. Immunotherapy—an approach that activates the immune system to fight cancer—has been effective in other cancers but has shown limited success in PC.This is largely due to the tumor’s ability to suppress immune responses and create an environment that protects it from attack. Currently, these drugs are only approved for a small subset of patients whose tumors have a specific genetic feature called high microsatellite instability (MSI-high), found in just 1 to 2 percent of cases.The Study: Pancreatic Cancer Immunotherapy RespondersThe study, titled “Exceptional responders to immunotherapy in pancreatic cancer: A multi-institutional case series of a rare occurrence,” was led by first author Kavin Sugumar and corresponding author Jordan M. Winter, from University Hospitals Seidman Cancer Center.The researchers examined medical records from 14 patients with pancreatic ductal adenocarcinoma (PDAC) who had responded unexpectedly well to immune checkpoint inhibitors—drugs that help reactivate immune cells to attack cancer. The drugs included PD-1 inhibitors such as pembrolizumab and nivolumab, CTLA-4 inhibitors like ipilimumab, and agents targeting tumor-associated macrophages. To find these rare cases, the research team contacted 471 oncologists from 91 major U.S. cancer centers between 2020 and 2021.Full blog - https://www.oncotarget.org/2025/09/11/immunotherapy-response-in-pancreatic-cancer-what-a-new-study-reveals/Paper DOI - https://doi.org/10.18632/oncotarget.28739Correspondence to - Jordan M. Winter - [email protected]Abstract video - https://www.youtube.com/watch?v=VeWTcuVmqgMSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28739Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, pancreatic adenocarcinoma, immunotherapy, exceptional responders, microsatellite instability, survivalTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh5 min
- Blocking Protein Control Pathway Slows Rhabdomyosarcoma Growth in MiceBUFFALO, NY – August 29, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 29, 2025, titled “In vivo manipulation of the protein homeostasis network in rhabdomyosarcoma.”In this study led by first author Kristen Kwong and corresponding author Amit J. Sabnis from the Department of Pediatrics, Division of Oncology, University of California San Francisco, researchers discovered that disrupting the protein quality control system in cancer cells slows tumor growth in rhabdomyosarcoma (RMS), the most common pediatric soft tissue cancer. This finding points to a new strategy for treating high-risk childhood cancers that often resist current therapies.Rhabdomyosarcoma is a rare and aggressive cancer that primarily affects children and adolescents. Standard treatments like chemotherapy and radiation often have limited long-term success in high-risk cases. This study explored a different approach: targeting the cellular machinery that maintains protein quality, known as the proteostasis network. Cancer cells rely heavily on this system to survive stress caused by rapid growth and genetic instability.“To examine whether MAL3-101 or more drug-like proteostasis inhibitors represent a new therapeutic strategy for RMS, we screened proteostasis components that might recapitulate the effects of MAL3-101 in vivo.”The researchers first used a compound called MAL3-101 to disrupt protein control in RMS cells. They then identified which parts of the protein quality system were affected. Based on those findings, they searched for more drug-like compounds that could target the same pathways.They focused on a protein called p97, which plays a critical role in removing damaged or misfolded proteins. When they blocked p97 using a drug called CB-5083, the cancer cells could no longer manage internal stress and began to self-destruct. In both laboratory models and mice implanted with human RMS tumors, the treatment significantly slowed or stopped tumor growth. The drug triggered a stress response in the cells known as the unfolded protein response, which can lead to either recovery or programmed cell death.However, not all tumors responded the same way. Some resisted the treatment by activating a backup system called autophagy, which allows cells to recycle parts of themselves under stress. By comparing tumors that responded well to those that did not, the researchers found that higher autophagy activity could serve as a warning sign for resistance. This insight may help identify which patients are more likely to benefit from therapies that target protein quality control.While the results are promising, the drug’s effectiveness depended on the tumor’s genetic profile and how it handled stress. Combining p97 inhibition with other treatments or blocking alternative survival pathways like autophagy may improve outcomes. The researchers also noted the importance of developing safer and more targeted drugs to reduce side effects.This study opens new possibilities for personalized cancer treatment, particularly for children with aggressive or relapsed RMS. By weakening the systems that cancer cells depend on to survive, rather than only using toxic treatments to kill them, scientists aim to develop more effective and less harmful therapies for young patients.DOI - https://doi.org/10.18632/oncotarget.28764Correspondence to - Amit J. Sabnis - [email protected]Video short - https://www.youtube.com/watch?v=YsdffTkXNRQTo learn more about Oncotarget, visit https://www.oncotarget.com.Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh4 min
- Behind the Study: R-spondin Family Roles in Metastatic Prostate CancerAiden Deacon from the University of Minnesota-Twin Cities, Minneapolis, discusses a research paper he co-authored that was published in Volume 16 of Oncotarget, titled “Dissecting the functional differences and clinical features of R-spondin family members in metastatic prostate cancer.”DOI - https://doi.org/10.18632/oncotarget.28758Correspondence to - Justin Hwang - [email protected]Video interview - https://www.youtube.com/watch?v=OXKhWWU1gnYAbstractThis study investigates the R-spondin family of genes (RSPO1/2/3/4), a group of secreted proteins that act as Wnt regulators, and their subsequent role in advanced prostate cancer (PC). When evaluating transcriptomic data from primary and metastatic PC patients, we found that alterations in RSPO2 were more prevalent than in other RSPO family members or Wnt-regulating genes APC and CTNNB1. Further, we found that RSPO2 alterations in PCs were significantly associated with worse disease-free survival. Through our in silico modeling, RSPO2 exhibited strong positive associations with genes regulating epithelial-mesenchymal transition (EMT) and double-negative prostate cancer (DNPC), but had negative correlations with androgen receptor (AR) and AR-associated genes. Furthermore, 3D modeling of RSPO2 revealed structural differences between itself and other RSPOs. In cell lines, RSPO2 overexpression caused up-regulation of EMT pathways, including EMT-regulatory transcription factors ZEB1, ZEB2, and TWIST1. Conversely, this was not observed when CTNNB1 was overexpressed in the same models. These findings highlight that, in PC, RSPO2 functions as a unique member of the R-spondin family by promoting genes and signaling pathways associated with aggressive PC, and RSPO2 amplifications are associated with poor outcomes in PC patients.Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28758Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, RSPO2, prostate cancer, Wnt signaling, genomics, therapeuticsAbout OncotargetOncotarget (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).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/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh8 min
- Amivantamab Monotherapy in Rare EGFR-Mutated Advanced NSCLCNon-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. While the development of targeted therapies has improved outcomes for many patients with EGFR-mutated NSCLC, those with rare EGFR variants often face limited treatment options, especially when the disease involves the central nervous system (CNS).A recent research paper, titled “Durable complete response in leptomeningeal disease of EGFR mutated non-small cell lung cancer to amivantamab, an EGFR-MET receptor bispecific antibody, after progressing on osimertinib” published in Volume 16 of Oncotarget, describes a patient with NSCLC harboring two uncommon EGFR mutations—G719A and A289V—who experienced a prolonged and clinically significant response to amivantamab monotherapy, after prior treatments had failed.Full blog - https://www.oncotarget.org/2025/08/26/amivantamab-monotherapy-in-rare-egfr-mutated-advanced-nsclc/Paper DOI - https://doi.org/10.18632/oncotarget.28730Correspondence to - Young Kwang Chae - [email protected]Video short - https://www.youtube.com/watch?v=UEiCz834a8cSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28730Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, amivantamab, monotherapy, rare EGFR mutation, NSCLC, leptomeningeal diseaseAbout OncotargetOncotarget (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).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/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh6 min
- Aramchol Boosts Regorafenib Effectiveness in Gastrointestinal TumorsBUFFALO, NY – August 19, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 19, 2025, titled “The SCD1 inhibitor aramchol interacts with regorafenib to kill GI tumor cells in vitro and in vivo.”In this study, led by first authors Laurence Booth and Michael R. Booth, along with corresponding author Paul Dent from Virginia Commonwealth University, researchers investigated how aramchol, a drug originally developed for liver disease, works with the cancer drug regorafenib in gastrointestinal (GI) tumor cells. They found that the combination is effective, especially in tumor cells with a specific genetic variant. The combined approach offers a potential new strategy for treating liver and colon cancers.Gastrointestinal cancers, such as liver and colon cancer, are serious global health challenges. Regorafenib, already approved for cancer treatment, can have limited impact and frequently causes side effects. Aramchol, a drug developed to treat fatty liver disease, affects how cancer cells process fats and energy. In this study, researchers tested whether combining these two drugs could improve GI cancer treatment, both in cells and mouse models.The results showed that the drug combination killed liver and colorectal cancer cells more effectively than either drug alone. In animal models, mice with human liver tumors had slower tumor growth, without showing signs of weight loss or other toxicity.The researchers also found that aramchol and regorafenib work together to block important survival pathways inside cancer cells. This combination was especially effective in cells with a genetic variant called ATG16L1 T300, which is more common in people of African ancestry. The treatment triggered stress responses in the cancer cells and disrupted key proteins required for survival. It also activated autophagy, a natural recycling process that clears out damaged parts, eventually leading to cancer cell death.“Aramchol interacted with the multi-kinase inhibitors sorafenib, regorafenib or lenvatinib, to kill GI tumor cells, with regorafenib exhibiting the greatest effect.”Aramchol is currently in clinical trials for fatty liver disease and has a well-established safety profile, while regorafenib is already FDA-approved for cancer treatment. Together, their combination could advance fast into clinical testing for patients with GI cancers. However, researchers note that additional studies are needed to support the launch of early-phase clinical trials.Altogether, this study may offer a more effective and less toxic alternative to current treatments for GI cancers. It also highlights the role of genetic variants in shaping treatment response, suggesting that future therapies could be more precisely tailored to each patient’s unique genetic profile.DOI - https://doi.org/10.18632/oncotarget.28762Correspondence to - Paul Dent - [email protected]Video short - https://www.youtube.com/watch?v=5saAqsqxi-QSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28762Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, macroautophagy, flux; ER stress, aramchol, regorafenibTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh4 min
- FDA-Approved MI Cancer Seek Test Enhances Tumor Profiling for Precision OncologyBUFFALO, NY – August 15, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 13, 2025, titled “Clinical and analytical validation of MI Cancer Seek®, a companion diagnostic whole exome and whole transcriptome sequencing-based comprehensive molecular profiling assay.”In this study, first authors Valeriy Domenyuk and Kasey Benson, along with corresponding author David Spetzler from Caris Life Sciences in Irving, Texas, introduce MI Cancer Seek, an FDA-approved test designed to deliver comprehensive tumor profiling. MI Cancer Seek demonstrated strong concordance with other FDA-approved companion diagnostics and serves as a powerful tool to guide treatment decisions in both adult and pediatric cancer patients.Cancer remains one of the most complex and diverse diseases to treat. With many targeted therapies currently FDA-approved, selecting the right one for a specific patient requires detailed genetic insights. MI Cancer Seek addresses this need by analyzing both DNA and RNA from a single tumor sample. The tool identifies key biomarkers linked to FDA-approved treatments for several major cancers, including breast, lung, colon, melanoma, and endometrial cancers.One of the most significant strengths of MI Cancer Seek is its ability to deliver accurate and reliable results from minimal tissue input (50 ng). Even when analyzing formalin-fixed paraffin-embedded samples, which are widely used but often degraded, the test maintained high levels of accuracy. It successfully detected important genetic alterations such as PIK3CA, EGFR, BRAF, and KRAS/NRAS mutations and measured tumor mutational burden (TMB) and microsatellite instability (MSI), both of which are key indicators for immunotherapy response.In clinical comparisons, the test achieved over 97% agreement with other FDA-approved diagnostic tools, confirming its reliability in detecting critical biomarkers. Notably, it showed near-perfect accuracy in identifying MSI status in colorectal and endometrial cancers. The researchers also demonstrated that the test maintains precision across different lab conditions and varying DNA input levels, confirming its robustness for routine clinical use.Beyond its role as a companion diagnostic, MI Cancer Seek incorporates additional features developed under its predecessor, MI Tumor Seek Hybrid. These include detection of homologous recombination deficiency, structural variants, and cancer-related viruses. It also includes advanced tools such as the Genomic Probability Score for identifying the tissue of origin in cancers of unknown primary, as well as a gene signature to guide first-line chemotherapy in colorectal cancer.“One limitation to be considered is the low PPA for ERBB2 CNA detection.”By offering deeper genetic insights from a single, small sample, MI Cancer Seek has the potential to streamline diagnostics, reduce testing costs, and connect patients to effective therapies more quickly. As precision medicine continues to expand, this assay stands out as a comprehensive and efficient solution for meeting the evolving needs of modern oncology.DOI - https://doi.org/10.18632/oncotarget.28761Correspondence to - David Spetzler - [email protected]Video short - https://www.youtube.com/watch?v=D4hd2FxCYY8Subscribe 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/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh5 min
- New Compound Disrupts Survival Pathways in Aromatase Inhibitor-Resistant Breast Cancer CellsBUFFALO, NY - August 13, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 29, 2025, titled “PCAIs stimulate MAPK, PI3K/AKT pathways and ROS-Mediated apoptosis in aromatase inhibitor-resistant breast cancer cells while disrupting actin filaments and focal adhesion.”In this study, led by first author Jassy Mary S. Lazarte and corresponding author Nazarius S. Lamango from Florida A&M University College of Pharmacy and Pharmaceutical Sciences, researchers investigated a new class of compounds called polyisoprenylated cysteinyl amide inhibitors (PCAIs) as a potential treatment for aromatase inhibitor (AI) therapy resistant breast cancer. Aromatase inhibitors are a common treatment for estrogen receptor-positive (ER+) breast cancer, but many patients eventually develop resistance, leaving fewer therapeutic options.The study focused on a PCAI compound called NSL-YHJ-2-27, which was tested in long-term letrozole-treated breast cancer cells (LTLT-Ca), an experimental model of AI therapy resistance. NSL-YHJ-2-27 activated two major signaling pathways, MAPK and PI3K/AKT. Although these pathways typically support cancer cell survival, their overstimulation by PCAIs led to increased oxidative stress, damaging the cells and inducing cell death by apoptosis. The compound also reduced levels of RAC1 and CDC42, proteins involved in maintaining cell shape and movement. These alterations resulted in cytoskeletal disruption and reduced structural integrity, making the cancer cells more vulnerable and less capable of spreading. Importantly, the effects of NSL-YHJ-2-27 persisted after the compound was removed, suggesting long-term control over AI resistant cancer cells may be possible.“PCAIs inhibited cell proliferation and colony formation by 95% and 74%, respectively, increased active caspase 7 and BAX 1.5-fold and 56%, respectively. NSL-YHJ-2-27 (10 μM) induced LTLT-Ca spheroid degeneration by 61%.”As a new class of targeted molecules, PCAIs represent an innovative approach distinct from traditional endocrine therapies. Their ability to affect multiple cellular mechanisms simultaneously makes them promising candidates for future drug development.Overall, this study presents a promising new approach for treating AI therapy-resistant breast cancer. By targeting cellular pathways that support survival and mobility, PCAIs like NSL-YHJ-2-27 could provide a novel strategy to manage advanced or resistant forms of the disease. Further research, including in vivo studies and clinical trials, will be essential to confirm these findings and evaluate their therapeutic potential.DOI - https://doi.org/10.18632/oncotarget.28759Correspondence to - Nazarius S. Lamango - [email protected]Video short - https://www.youtube.com/watch?v=8xQEilloO9QSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28759Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, PCAIs, ROS, MAPK, PI3K/AKT, LTLT-Ca cellsTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh4 min
- Cigarette Smoke and Weak DNA Repair: A Double Hit Behind Lung Cancer RiskLung cancer, particularly non-small cell lung cancer (NSCLC), is the deadliest cancer worldwide. Cigarette smoking is one of the main causes, but not every smoker develops the disease. This suggests that other biological factors help determine who develops cancer.Researchers from the Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indianapolis, and from the Richard L. Roudebush Veterans Affairs Medical Center have now found that cigarette smoke, combined with a weakened DNA repair system, can trigger the early stages of lung cancer, particularly NSCLC. This work, led by first author Nawar Al Nasralla and corresponding author Catherine R. Sears, was recently published in Volume 16 of Oncotarget.Full blog - https://www.oncotarget.org/2025/08/11/cigarette-smoke-and-weak-dna-repair-a-double-hit-behind-lung-cancer-risk/Paper DOI - https://doi.org/10.18632/oncotarget.28724Correspondence to - Catherine R. Sears - [email protected]Video short - https://www.youtube.com/watch?v=UEiCz834a8cSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28724Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, DNA repair, DNA damage, lung adenocarcinoma, squamous cell carcinoma, Xeroderma Pigmentosum Group C (XPC)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/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh6 min
- New Gene Linked to Aggressive, Treatment-Resistant Prostate CancerBUFFALO, NY – August 11, 2025 – A new #researchpaper was #published in Volume 16 of Oncotarget on July 25, 2025, titled “Dissecting the functional differences and clinical features of R-spondin family members in metastatic prostate cancer.”In this study, researchers led by first author Aiden Deacon and corresponding author Justin Hwang from the University of Minnesota-Twin Cities investigated a group of genes known as the R-spondin family (RSPO1/2/3/4) in advanced prostate cancer (PC). The RSPO gene family regulates Wnt signaling, a pathway involved in cancer progression.Prostate cancer is the most common cancer among men in the United States and becomes especially dangerous when it spreads beyond the prostate. Most patients are treated with hormone therapies that target the androgen receptor; however, many tumors eventually become resistant.The research team analyzed thousands of tumor samples and found that RSPO2 alterations were more common than changes in other R-spondin genes or even some well-known cancer-related genes like CTNNB1 and APC. RSPO2 amplification occurred in over 20% of metastatic prostate cancer. Patients with these alterations showed signs of more aggressive disease, including higher mutation rates and greater tumor complexity.Using laboratory models, the team discovered that RSPO2 increases cancer cell growth and triggers a biological process called epithelial-mesenchymal transition (EMT). EMT is known to promote tumor spread and resistance to standard treatments. Unlike other genes in the same pathway, RSPO2 also appeared to reduce the activity of androgen receptor genes, suggesting it drives a type of prostate cancer that no longer relies on hormones for growth.“In cell lines, RSPO2 overexpression caused up-regulation of EMT pathways, including EMT-regulatory transcription factors ZEB1, ZEB2, and TWIST1.”Importantly, RSPO2 showed structural differences from other R-spondin proteins, which may allow researchers to design drugs that specifically block its activity. Current therapies targeting the Wnt pathway are limited, and there are no approved drugs that inhibit RSPO2. However, this study highlights RSPO2 as a promising therapeutic target, especially for patients who do not respond to existing hormone-based treatments.This research adds critical knowledge about how aggressive prostate cancers develop and persist despite therapy. The identification of RSPO2 as a key driver of disease progression opens new possibilities for treatment strategies aimed at improving outcomes for patients with advanced prostate cancer.DOI - https://doi.org/10.18632/oncotarget.28758Correspondence to - Justin Hwang - [email protected]Video short - https://www.youtube.com/watch?v=iyu5D_c1dbYSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28758Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, RSPO2, prostate cancer, Wnt signaling, genomics, therapeuticsTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh4 min
- A New Way to Target Resistant Prostate Cancer CellsProstate cancer is the second most diagnosed cancer among men worldwide and remains a leading cause of cancer-related death. While early forms of the disease can usually be treated successfully, advanced cases remain a major challenge. Scientists have now discovered a new potential way to slow the growth of advanced, treatment-resistant prostate cancer. These results were recently published in Volume 16 of Oncotarget by researchers from the University of Cincinnati College of Medicine.Understanding Advanced Prostate CancerEarly-stage prostate cancer can often be treated successfully. Most treatments work by lowering testosterone levels or blocking the hormone from activating the androgen receptor (AR), which drives cancer growth.In some patients, however, the disease progresses to castration-resistant prostate cancer (CRPC). Even with drastic reductions in testosterone levels, the tumors continue to grow at this stage. CRPC is much more difficult to treat, and current therapies such as hormone blockers or chemotherapy typically extend life by only a few months.One reason for this resistance is that cancer cells often switch to a different form of the androgen receptor called AR-V7. This variant remains permanently active, even without testosterone, making hormone-based drugs less effective. Because of this, new treatment strategies that work independently of hormone levels are needed.The Study: Targeting a New Weakness in Prostate Cancer CellsIn the study titled “Targeting PCNA/AR interaction inhibits AR-mediated signaling in castration resistant prostate cancer cells,” researchers Shan Lu and Zhongyun Dong from the University of Cincinnati College of Medicine investigated a new way to block CRPC growth.Full blog - https://www.oncotarget.org/2025/07/29/a-new-way-to-target-resistant-prostate-cancer-cells/Paper DOI - https://doi.org/10.18632/oncotarget.28722Correspondence to - Zhongyun Dong - [email protected]Video short - https://www.youtube.com/watch?v=fiJWZ_fKxgsSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28722Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, PCNA, androgen receptor, PCNA inhibitors, AR splicing variants, CRPCTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh6 min
About Oncotarget
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Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.
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