Oncotarget最新文献

{"title":"WIN-MTB-2024002 - WIN International Molecular Tumor Board: A 52-year-old female with unmeasurable Stage IIIc colon cancer.","authors":"Wafik S El-Deiry, Alberto Hernando-Calvo, Shai Magidi, Catherine Bresson, Sadakatsu Ikeda, Hikmat Abdel-Razeq, Arjun Oberoi, Susana Aguilar Izquierdo, Zhihuang Hu, Tobias Meissner, Rachel Elsey, Amal Al-Omari, Fanny Wunder, Razelle Kurzrock","doi":"10.18632/oncotarget.28921","DOIUrl":"https://doi.org/10.18632/oncotarget.28921","url":null,"abstract":"<p><p>Copyright: &copy; 2026 El-Deiry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with a complex molecular profile that impacts tumor behavior and treatment response. This case report discusses a 52-year-old female diagnosed with Stage IIIc colon cancer, exhibiting KRAS, TP53, IDH1, and APC mutations, as well as a tumor microenvironment with high PD-L1 expression and elevated VEGFR1 and VEGFR3. Despite surgical resection and adjuvant treatment which included FOLFOX, FOLFIRI with bevacizumab and local radiation, the patient&#x2019;s disease was difficult to track due to small, non-FDG-avid lymph nodes in the aortocaval region and persistent circulating tumor DNA (ctDNA). Following a review by an international Molecular Tumor Board (MTB), maintenance therapy options were discussed, including the personalized combinations of regorafenib, sulindac, and metformin, or fruquintinib, sulindac, and metformin, based on the patient&#x2019;s molecular alterations. Alternatively, 5-FU with or without bevacizumab was suggested. In the event of relapse, the MTB recommended the combination of regorafenib, sulindac, and metformin, with the addition of trametinib and ivosidenib. The combination of regorafenib, ipilimumab, and nivolumab (RIN) was also considered due to the patient&#x2019;s high PD-L1 expression. Further clinical trial options, such as pan-RAF inhibitors, NK cell agonists, and TAS-102 with bevacizumab, were also discussed. Additionally, the potential combination of PD-1 and TGF&#x03B2; inhibitors was explored. This case underscores the critical role of molecular profiling in tailoring personalized treatment strategies for advanced CRC, providing novel avenues for managing recurrent disease, even in the absence of measurable disease.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"17 1","pages":"477-488"},"PeriodicalIF":0.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report WIN-MTB-2024001 - WIN International Molecular Tumor Board: A 55-year-old male with glioblastoma exhibiting amplifications in MDM2 and EGFR.","authors":"Wafik S El-Deiry, Sadakatsu Ikeda, Shai Magidi, Catherine Bresson, Hikmat Abdel-Razeq, Anthony Joshua, Alberto Hernando-Calvo, Arjun Oberoi, Zhihuang Hu, Tobias Meissner, Rachel Elsey, Amal Al-Omari, Fanny Wunder, Razelle Kurzrock","doi":"10.18632/oncotarget.28920","DOIUrl":"https://doi.org/10.18632/oncotarget.28920","url":null,"abstract":"<p><p>Copyright: &copy; 2026 El-Deiry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The WIN Consortium International Molecular Tumor Board brings together precision oncology experts from 18 organizations in 13 countries across four continents and provides discussion for patients with cancer across the world. This case report details the medical journey of a 55-year-old man diagnosed with high-grade glioblastoma (GBM), characterized by amplifications of MDM2 and EGFR, alongside other critical genomic alterations, including a CDKN2A frameshift mutation. Despite the aggressive nature of GBM, the patient was in remission following a combination of radiotherapy and chemotherapy, surgery and participation in a phase II clinical trial (PI3K/mTOR inhibitor) combined with ketogenic diet and metformin. However, the patient was also considering personalized neoantigen vaccine therapy targeting tumor-specific mutated peptides as part of his treatment strategy. This case underscores the immense complexity of treating GBM. Next generation sequencing showed MDM2 amplification, which hinders the tumor-suppressive functions of p53, and EGFR amplification, which promotes oncogenic signaling. The experts highlighted various therapeutic options discussed in the event of relapse: EGFR inhibitors, various MDM2 inhibitors, and personalized combination therapies targeting both EGFR and CDK4/6. Additionally, the Molecular Tumor Board discussed the reported risk of resistance or hyper-progression with immune checkpoint blockade in the presence of EGFR and MDM2 alterations. Innovative approaches such as combining MDM2 and EGFR inhibitors with immunotherapy, as well as the use of teserpaturev, a genetically engineered herpes simplex virus were addressed. This case emphasizes the importance of personalized treatment strategies for GBM and the need for ongoing clinical research to explore novel therapeutic options.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"17 1","pages":"462-475"},"PeriodicalIF":0.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative pan-cancer analysis of AKT1 and structure-based drug design by buckwheat derived compounds.","authors":"Ramjan Sheikh, Punam Chowdhury, Ekhlas Uddin, Jarin Tasnim, Mobin Mahmud Shawon, Sohela Faisal, Abu Sayed, M Salahuddin, Abrar Farhan Fuad","doi":"10.18632/oncotarget.28922","DOIUrl":"https://doi.org/10.18632/oncotarget.28922","url":null,"abstract":"<p><p>Copyright: &copy; 2026 Sheikh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. AKT1 is a serine-threonine protein-kinase involved in tumour cell proliferation, survival, metabolism, and therapeutic resistance via activation of the PI3K/AKT/mTOR pathway. However, the comprehensive pan-cancer characterization of AKT1 and systematics identifications of natural AKT1 inhibitors remains limited. This study comprehensively evaluated the expression patterns and mutation landscape of AKT1, its promoter methylation, immune infiltration, and clinical significance using the TCGA datasets for 33 cancer types. AKT1 showed significant over-expression in BRCA, HNSC, CHOL, STAD, and UCEC while being under-expressed in PRAD and GBM. Survival analysis demonstrated cancer-specific prognostic associations of AKT1 expression, and cBioPortal profiling characterized E17 as having hotspot missense mutations. Promoter methylation profiling revealed widespread hypomethylation that correlates with increased transcription. AKT1 was widely expressed in normal tissues, and its localization was mainly cytoplasmic, varying according to cell type. At the single cell level, expression was detected in malignant, immune, and stromal compartments. AKT1 expression exhibited tumor-specific associations with tumor mutational burden and microsatellite instability. To identify candidate natural inhibitors, this study computationally screened 52 buckwheat-derived phytochemicals with AKT1. Fagopyrine showed the strongest binding affinity (&#x2212;15.45 kcal/mol) and remained structurally stable and flexible with AKT1 protein at 100 ns MD simulation. ADMET and DFT analyses indicated favorable electronic stability but predicted moderate gastrointestinal absorption, suggesting that further structural optimization is required. In summary, this study reveals that fagopyrine is a promising computational AKT1 targeting lead, but the direct biochemical and cancer cell-line validation experiments required to confirm its AKT1 inhibitory activity and anticancer efficacy remain to be performed.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"17 1","pages":"437-461"},"PeriodicalIF":0.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are both COVID-19 and COVID-19 vaccines associated with cancer?","authors":"Raphael Lataster","doi":"10.18632/oncotarget.28918","DOIUrl":"10.18632/oncotarget.28918","url":null,"abstract":"<p><p>Copyright: &copy; 2026 Lataster. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"17 1","pages":"426-427"},"PeriodicalIF":0.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-expression of MHC-I to treat CNS cancers.","authors":"Arseniy E Yuzhalin","doi":"10.18632/oncotarget.28917","DOIUrl":"10.18632/oncotarget.28917","url":null,"abstract":"<p><p>Copyright: &copy; 2026 Yuzhalin. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Immunologically &#x201C;cold&#x201D; malignant tumors of the central nervous system (CNS) evade immune surveillance largely through downregulation or loss of major histocompatibility complex class I (MHC-I), impairing CD8+ T cell-mediated elimination and contributing to poor prognosis. I discuss multiple strategies to restore MHC-I expression in brain cancers, including epigenetic modulation with histone deacetylase (HDAC) and DNA methyltransferase inhibitors, adeno-associated virus (AAV)-based gene therapy for direct human leukocyte antigen (HLA) class I or transcription factor delivery, and modulation of the tumor microenvironment to enhance antigen presentation. In addition, targeting autophagy and addressing genetic HLA losses are discussed as critical considerations. Effective MHC-I restoration may require integrated approaches that also enhance antigen processing and neoantigen presentation. Overcoming CNS-specific barriers and combining MHC-I re-expression with immunotherapy and chemoradiotherapy could unlock new therapeutic avenues against CNS malignancies.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"17 1","pages":"414-425"},"PeriodicalIF":0.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging biomedical imaging applications of tumor-derived extracellular vesicles for premetastatic niche detection: Biological rationale, engineering strategies, and translational challenges.","authors":"Omkar Dhaygude, Yun Chen, Yamauchi Suguru, Malcom Brock, Franck Housseau, John Michel","doi":"10.18632/oncotarget.28916","DOIUrl":"https://doi.org/10.18632/oncotarget.28916","url":null,"abstract":"<p><p>Copyright: &copy; 2026 Dhaygude et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Extracellular vesicles (EVs) are a heterogeneous population of membrane-enclosed nanoparticles naturally released by virtually all cell types, including exosomes, microvesicles, and other vesicular subtypes that differ in biogenesis, size, and molecular composition. By transporting proteins, lipids, nucleic acids, and metabolites, EVs mediate local and systemic intercellular communication and play a central role in tumor progression, organ-specific metastasis, and remodeling of distant microenvironments. Recent advances in EV isolation, engineering, and molecular profiling have accelerated interest in their use as nanomedicine platforms for both targeted delivery and cancer diagnostics. In particular, tumor-derived EVs (TEVs) exhibit intrinsic organotropism and participate in the establishment of premetastatic niches, making them promising vehicles for the targeted delivery of imaging probes to metastasis-prone tissues. This review discusses the emerging use of EVs as carriers of contrast and molecular imaging agents to enable visualization of premetastatic niches before overt metastatic lesions become detectable by conventional imaging modalities such as computed tomography. We highlight the biological rationale, engineering strategies, imaging applications, and translational challenges associated with EV-based probe delivery and consider how this approach may improve early detection of metastatic spread, risk stratification, and disease monitoring in oncology.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"17 1","pages":"389-412"},"PeriodicalIF":0.0,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of <i>KRAS</i> G12C mutations in genitourinary malignancies; emerging target in precision medicine.","authors":"Kelly Crane, K R Seetharam Bhat, P Grivas, Andrea Necchi, Gennady Bratslavsky, Oleg Shapiro, Joseph M Jacob, Hanan Goldberg, Rebecca Sager, Jeffery S Ross","doi":"10.18632/oncotarget.28912","DOIUrl":"10.18632/oncotarget.28912","url":null,"abstract":"<p><p>Copyright: &copy; 2026 Crane et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p><p><strong>Purpose: </strong>The discovery of KRAS G12C as a therapeutic target has transformed oncology with the development of specific inhibitors. This study aimed to characterize the prevalence and clinicogenomic features of KRAS G12C mutations in genitourinary malignancies, an area with limited prior data despite recent FDA approvals of KRAS G12C-targeted therapies.</p><p><strong>Materials and methods: </strong>Comprehensive genomic profiling was performed on 13,654 formalin-fixed paraffin-embedded specimens, including 1,453 renal clear cell carcinomas (RCCC), 3,879 urothelial bladder carcinomas (UBC), and 8,322 prostate acinar adenocarcinomas (PAAC). Tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression (Dako 22C3) were also assessed.</p><p><strong>Results: </strong>KRAS alterations were identified in 7 RCCC (&lt;1%), 202 UBC (5.2%), and 158 PAAC (1.9%) cases. KRAS G12C variants were detected in 0 RCCC (0%), 24 UBC (12%), and 1 PAAC (&lt;1%) cases. No KRAS G12C-mutated tumors showed MSI-high status. In UBC, KRAS G12C-positive cases demonstrated significantly lower TERT co-mutations and higher KDM6A alterations compared to KRAS G12C-negative cases (both p &lt; 0.05). Age and sex distributions were similar across subtypes. Predominant co-alterations included VHL, SETD2, and PBRM1 in RCCC, and TP53, CDKN2A, and TERT in UBC.</p><p><strong>Conclusions: </strong>KRAS G12C mutations occur infrequently in major genitourinary malignancies. However, given the expanding therapeutic landscape of KRAS G12C inhibitors and potential for basket trials, further investigation in bladder and prostate cancers is warranted. These agents may offer meaningful benefit to the small subset of patients harboring this actionable alteration.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"17 1","pages":"381-387"},"PeriodicalIF":0.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic methodological flaws in DNA contamination assessment of mRNA vaccines: A critical analysis of Achs et al. (2025).","authors":"Kevin McKernan, David J Speicher, Jessica Rose","doi":"10.18632/oncotarget.28913","DOIUrl":"10.18632/oncotarget.28913","url":null,"abstract":"<p><p>Copyright: &copy; 2026 McKernan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Recent work by Achs et al. (2025) claimed to demonstrate no excessive residual DNA in COVID-19 mRNA vaccines using four orthogonal approaches. Since this work is being cited by regulatory authorities to claim DNA levels in mRNA vaccines are within limits, it is imperative that a robust public discussion occur regarding the methods strengths and weaknesses. We present a comprehensive critique identifying critical methodological flaws that systematically bias results toward underestimation of residual DNA contamination. These include: (1) inappropriate plasmid molecular weight calculations producing 1.5&#x2013;10&#x00D7; underestimation (plasmid equivalents), (2) fragment size bias in primer design favoring detection of non-functional sequences over spike-encoding DNA, (3) thermal degradation of samples during library preparation, (4) analytical detection limits exceeding regulatory thresholds, (5) platform limitations excluding detection of kilobase-length DNA fragments, and (6) failure to account for RNA:DNA hybrid formation protecting spike DNA from degradation. Collectively, these flaws render the study&#x0027;s conclusions invalid for regulatory assessment of residual DNA contamination.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"17 1","pages":"368-376"},"PeriodicalIF":0.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed growth of SK-ES-1 Ewing sarcoma tumor xenografts is associated with reduced Trk and IGF1R pathway markers.","authors":"Bruna Almeida Dos Santos, Nat xE Lia Hogetop Freire, Livia Fratini, Matheus Dalmolin, Josimar Macedo de Castro, Marcelo A C Fernandes, Lauro Gregianin, Andr xE T Brunetto, Algemir Lunardi Brunetto, Luis Fernando da Rosa Rivero, Mariane da Cunha Jaeger, Rafael Roesler, Caroline Brunetto de Farias","doi":"10.18632/oncotarget.28911","DOIUrl":"10.18632/oncotarget.28911","url":null,"abstract":"<p><p>Copyright: &copy; 2026 dos Santos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Ewing sarcoma (ES) is an aggressive childhood tumor. We have previously shown that tropomyosin receptor kinase (Trk) neurotrophin receptors regulate viability, and the Trk and multi-kinase inhibitor K252a restores sensitivity to chemotherapy, in ES cells. Here, we show that administration of K252a in mice transiently delays ES tumor growth and reduces expression and phosphorylation of multiple targets. BALB/c nu/nu nude mice inoculated with SK-ES-1 ES cells were given daily intraperitoneal (i.p.) injections of K252a for 18 days. Immunohistochemical analysis of tumors was performed to quantify the expression and phosphorylation of Trk receptors, phosphoinositide 3-kinase (PI3K), and insulin-like growth factor 1 receptor (IGF1R). Treatment with K252a led to a partial and transient delay in ES tumor growth and reduced the expression and phosphorylation of TrkA, TrkB, PI3K, and IGF1R. Combined treatment with K252a and the IGF1R inhibitor NVP-ADW742 was more effective in reducing ES cell viability than each compound alone. Associations between genes encoding Trks, PI3K, and IGF1R and overall survival (OS) in patients with ES was examined. Significant associations between expression of NTRK genes and patient OS were found, indicating that NTRK genes should be further evaluated as biomarkers for prognosis in patients with ES.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"17 1","pages":"354-367"},"PeriodicalIF":0.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WIN-MTB-2024017 - WIN International Molecular Tumor Board: A 48-year-old female with multiple primary cancers.","authors":"Wafik S El-Deiry, Alberto Hernando-Calvo, Don Dizon, Shai Magidi, Catherine Bresson, Liang Cheng, Jia Liu, Zhihuang Hu, Crystal Hattum, Tobias Meissner, Ricky Grisson, Liu Liu, Arjun Oberoi, Naftali Z Frankel, Fanny Wunder, Razelle Kurzrock","doi":"10.18632/oncotarget.28899","DOIUrl":"10.18632/oncotarget.28899","url":null,"abstract":"<p><p>Copyright: &copy; 2026 El-Deiry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Multiple primary cancers (MPC), the occurrence of two or more distinct malignancies in the same patient, pose significant clinical challenges due to their complexity and the need for individualized treatment strategies. This case, discussed at the WIN Consortium International Molecular Tumor Board, illustrates the clinical journey of a 48-year-old female with a BRCA1 germline mutation who developed multiple primary cancers: breast, skin, high-grade serous carcinoma of the ovary, colon and small bowel cancers. Her treatment history included doxorubicin and cyclophosphamide for breast cancer, Mohs surgery for basal cell carcinoma, and carboplatin and paclitaxel for ovarian cancer. After participating in the PRIMA trial with niraparib, she was diagnosed with PIK3CA-mutated colon cancer, leading to resection and CAPOX chemotherapy. A subsequent diagnosis of small bowel adenocarcinoma, molecularly resembling her colon cancer, along with a unique BRCA1-STARD3 fusion in inguinal lymph nodes prompted a comprehensive MTB review. The panel discussed several precision strategies, including combinations of cetuximab, niraparib, and temsirolimus; FOLFIRI with anti-EGFR inhibitors; anti-CTLA-4 and anti-PD-1 (botensilimab and balstilimab); regorafenib with anti-CTLA-4 and anti-PD-1 (ipilimumab and nivolumab); trifluridine/tipiracil with bevacizumab; regorafenib alone; aspirin for potential benefits in patients with PIK3CA mutations; therapies targeting PIK3CA and EGFR alterations; regular imaging and liquid biopsies assessments for monitoring disease progression and guide future treatment decisions; and vaccines targeting PIK3CA, STARD3 and TP53. This case underscores the complexity of managing MPC and highlights the essential role of international molecular tumor boards in generating innovative, tailored treatment recommendations for patients with rare and multifaceted disease courses.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"17 1","pages":"341-352"},"PeriodicalIF":0.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}