Translational Oncology[JOURNAL]
Sun
200 papers
Targeting tryptophan metabolism in breast cancer immunotherapy: Recent advances and future prospects.
Li G, Zhou H, Shen X … +2 more , Ying P, Lu H
Transl Oncol · 2026 Aug · PMID 42224955 · Full text
Breast cancer (BC), a leading cause of cancer-related mortality in women, is predominantly characterized as an immunologically "cold" malignancy. This recalcitrant nature is largely attributed to its profound metabolic l...
Breast cancer (BC), a leading cause of cancer-related mortality in women, is predominantly characterized as an immunologically "cold" malignancy. This recalcitrant nature is largely attributed to its profound metabolic landscape, which orchestrates a hostile tumor microenvironment (TME). Central to this metabolic subversion is the kynurenine (Kyn) pathway of tryptophan (Trp) catabolism. Driven by the rate-limiting enzymes indoleamine 2,3-dioxygenase 1/2 (IDO1/2) and tryptophan 2,3-dioxygenase (TDO2), this axis functions as a critical molecular rheostat that promotes immune evasion by depleting essential Trp and accumulating bioactive Kyn metabolites. This review provides a comprehensive analysis of the molecular basis by which the Trp-Kyn-aryl hydrocarbon receptor (AhR) signaling axis impairs T-cell effector function, induces regulatory T-cell (Treg) differentiation, and modulates the plasticity of myeloid-derived suppressor cells (MDSCs) specifically within the BC context. We critically evaluate the clinical trajectory of first-generation IDO1 inhibitors, analyzing the biochemical and compensatory mechanisms-such as TDO2 upregulation-that contributed to recent clinical setbacks. Furthermore, we highlight emerging strategies, including dual IDO1/TDO2 inhibitors, AhR antagonists, and nanomedicine-based delivery systems designed to overcome metabolic barriers. By emphasizing the integration of Trp-targeted agents with immune checkpoint blockade and other conventional therapies, we propose a framework for biomarker-driven patient stratification. Ultimately, we outline future directions to transition from "one-size-fits-all" approaches toward precision metabolic immunotherapy to unlock robust anti-tumor immunity in breast cancer.
Progesterone induces steroidome and lipidome remodeling in a BRCA-resembling mouse model of high-grade serous ovarian cancer.
Schwiebert EM, Vega-Herrera A, Botros A … +5 more , Moore SG, Gaul DA, Kim O, Kim J, Fernández FM
Transl Oncol · 2026 Aug · PMID 42224954 · Full text
Ovarian cancer (OC) is the deadliest gynecological disease in women, with high-grade serous ovarian cancer (HGSC) being its most common and lethal subtype. This disease accounts for 75% of OC cases and has a five-year su...
Ovarian cancer (OC) is the deadliest gynecological disease in women, with high-grade serous ovarian cancer (HGSC) being its most common and lethal subtype. This disease accounts for 75% of OC cases and has a five-year survival rate of only 32%, mainly due to diagnoses at an advanced stage. Inheriting a pathogenic BRCA1 or 2 mutation significantly increases the risk of developing HGSC. However, the early molecular processes that lead to this deadly subtype remain poorly understood. The ovarian hormone progesterone (P4) has been shown to induce metastatic HGSC in Dicer1-Pten double-knockout (DKO) mice, an animal model that develops this specific type of OC with molecular, histological, and clinical features similar to those of BRCA1/2 mutation carriers. To explore P4-induced metabolic changes before and after the onset of HGSC, we analyzed serum samples from DKO mice treated with P4 or mifepristone, an inhibitor of P4 signaling, at premalignant and early tumor stages. These samples underwent both targeted and non-targeted metabolomic analysis using ultra-high performance liquid chromatography-mass spectrometry. The non-targeted data revealed significant trends among various phospholipid classes, phosphatidylcholines, sphingomyelins, and triacylglycerols, in early-stage HGSC. Additionally, two metabolites previously linked to OC, lysophosphatidylethanolamine (18:1) and tetrahydrocortisone, were significantly elevated at the premalignant stage of HGSC development. Conversely, at this same stage, the targeted dataset showed notable increases in estrogens and glucocorticoids, while higher corticosterone levels were detected as HGSC began to develop. Overall, this study highlights the disruption of specific metabolites, phospholipid classes, and steroid hormones, in relation to HGSC tumor development under P4 treatment, suggesting their potential roles in OC development.
Advances in deciphering intratumoral versus peritumoral heterogeneity of infiltrating lymphocytes in pancreatic cancer: a spatial perspective.
Zhao K, Yang Q, Yan Y … +2 more , Zhu J, Zheng S
Transl Oncol · 2026 Aug · PMID 42224953 · Full text
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by a profoundly immunosuppressive and spatially heterogeneous tumor microenvironment. Recent research has focused on the...
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by a profoundly immunosuppressive and spatially heterogeneous tumor microenvironment. Recent research has focused on the distinct topographic distribution of tumor-infiltrating lymphocytes (TILs) across intratumoral and peritumoral compartments. This review synthesizes the latest advances, delineating the distribution, functional states, and ontogeny of region-specific TIL subsets, and dissects how spatial heterogeneity fuels disease progression and resistance to immunotherapy. We further explore the reciprocal crosstalk between immunosuppressive stroma and lymphocyte heterogeneity, highlight prevailing technical and conceptual challenges, and outline emerging technologies poised to shape the next phase of discovery. This work provides a comprehensive roadmap to accelerate translation in PDAC immuno-oncology.
Current opinions on CEA in the diagnosis and prognosis of colorectal cancer.
Han Q, Zhu Y, Xing F … +1 more , Xia Y
Transl Oncol · 2026 Aug · PMID 42214175 · Full text
Colorectal cancer (CRC), marked by high mortality and recurrence rate, poses a significant threat to public health. Differences in survival rates exist, with patients in CRC stage IV much worse than those in stage I and...
Colorectal cancer (CRC), marked by high mortality and recurrence rate, poses a significant threat to public health. Differences in survival rates exist, with patients in CRC stage IV much worse than those in stage I and stage II. Carcinoembryonic antigen (CEA) has gained widespread use as a tumor marker for CRC. The method is easy to assess, inexpensive, noninvasive, with many advantages in monitoring the prognosis. However, its effectiveness in early detection of CRC leaves much to be desired. In this review, we summarized the current applications of CEA and discussed the innovative usage of CEA as a biomarker in CRC to facilitate a much more precise predictive and prognostic strategy. What's more, we concluded the biological features of CEA, involving its structure and gene regulation, and the roles of CEA in CRC progression and metastasis.
Combined treatment of TROP‑2 targeted CAR-T and vascular disruptor CBP enhances anti‑tumor activity in triple‑negative breast cancer.
Chen Y, Wang L, Jiang J … +9 more , Wei Y, Jiao P, JiaHu, Zhang W, Zhu J, Wang Y, Li X, Xiao F, Zhu L
Transl Oncol · 2026 Aug · PMID 42214174 · Full text
OBJECTIVES: This study aimed to investigate the synergistic potential of TROP-2-targeted CAR-T cells combined with the vascular disrupting agent PLG-g-mPEG/CA4/BLZ945 (CBP). We hypothesized that CBP would disrupt the tum...
OBJECTIVES: This study aimed to investigate the synergistic potential of TROP-2-targeted CAR-T cells combined with the vascular disrupting agent PLG-g-mPEG/CA4/BLZ945 (CBP). We hypothesized that CBP would disrupt the tumor neovascular, thereby enhancing infiltration of the CAR-T cells. METHODS: Analyzed TROP-2 expression in breast cancer using bioinformatics, qRT-PCR, and sequencing. Constructed and evaluated TROP-2 CAR-T cells in vitro. Finally, we prepared an animal model of breast cancer, and verified the anti-tumor therapeutic effect, safety evaluation and biologic mechanisms of TROP-2 CAR-T combined with CBP in vivo. RESULTS: Bioinformatics analysis and in vitro experiments showed that TROP-2 was widely expressed in breast cancer cells. The successfully constructed TROP-2 CAR-T cells exhibited high cytotoxicity in vitro. The experimental results in mice showed that the combination therapy of CBP and TROP-2 CAR-T significantly enhanced the anti-tumor effect, and no significant decrease in survival rate or major organ damage was observed. Mechanism studies have shown that the anti-tumor effect of the combination therapy group may be related to immune cell infiltration, CAR-T cell infiltration, and upregulation of immune related factors. CONCLUSION: Our findings demonstrated the potential of TROP-2 as a viable target for CAR-T therapy in breast cancer. The combination of TROP-2 CAR-T cells with CBP not only enhances the therapeutic efficacy but also maintains a favorable safety profile, offering a promising new strategy for the treatment of breast cancer.
Therapeutic vaccines targeting solid tumors: A series of clinical trial analysis over the past decade.
Qiu F, Sun Y, Lim DW
Transl Oncol · 2026 Aug · PMID 42208245 · Full text
Therapeutic cancer vaccines hold great promise, yet their clinical efficacy in solid tumors remains modest. We systematically analyzed 86 clinical trials published between 2015 and 2025 evaluating therapeutic vaccines ac...
Therapeutic cancer vaccines hold great promise, yet their clinical efficacy in solid tumors remains modest. We systematically analyzed 86 clinical trials published between 2015 and 2025 evaluating therapeutic vaccines across mRNA, DNA, peptide, dendritic cell, virus vector, and whole tumor cell platforms to understand their clinical utility and key challenges in development. Peptide-based vaccines dominated, while mRNA vaccines showed the fastest growth, often combined with immune checkpoint inhibitors. Among 1588 patients with advanced disease, the disease control rate was 53 % and the objective response rate 18 %. In adjuvant settings, 52 % of 461 patients experienced recurrence. Although 67 % exhibited ELISPOT-positive T-cell responses, no correlation with clinical efficacy was observed. Most adverse events were mild to moderate, with pyrexia, fatigue, and injection-site reactions predominating. Therapeutic vaccines thus demonstrate favorable safety and immunogenicity, but limited monotherapy efficacy, underscoring the need for combinatorial approaches and identifying personalized immunogenic neoantigens to enhance clinical benefit.
Sotorasib combined with 3-methyladenine for the treatment of KRAS G12C-mutant pancreatic cancer and its underlying mechanisms.
Li Y, Zhou M, Pan J … +9 more , Su H, Song M, Guan Z, Zhao D, Zhao X, Zhao Y, Chen P, Zhang S, Lv Y
Transl Oncol · 2026 Aug · PMID 42190605 · Full text
Pancreatic cancer is a gastrointestinal malignancy with an insidious onset and rapid progression. Due to limited therapeutic strategies, its mortality remains high. The KRAS gene is among the most frequently mutated gene...
Pancreatic cancer is a gastrointestinal malignancy with an insidious onset and rapid progression. Due to limited therapeutic strategies, its mortality remains high. The KRAS gene is among the most frequently mutated genes in solid tumors, and the development of drugs targeting KRAS mutations in pancreatic cancer is a current research focus. Sotorasib (AMG510) is the first small-molecule KRAS G12C-targeted inhibitor approved by the FDA for clinical use and has demonstrated safety and antitumor activity in tumors such as colorectal cancer and non-small cell lung cancer. At present, studies on the mechanisms of AMG510 in KRAS G12C-mutant pancreatic cancer are still at an early stage. This study aimed to investigate the effects of AMG510 on KRAS G12C-mutant pancreatic cancer cells and to preliminarily explore its mechanism of action. AMG510 inhibited the initiation and progression of KRAS G12C-mutant pancreatic cancer by inducing reactive oxygen species (ROS) accumulation, mitochondrial damage, cell cycle arrest, and apoptosis. RNA-seq revealed that AMG510 triggered cytoprotective autophagy in KRAS G12C-mutant pancreatic cancer. Treatment with the combination of AMG510 and the early autophagy inhibitor 3-methyladenine(3-MA) further suppressed proliferation and promoted apoptosis. Mouse experiments confirmed the biosafety and efficacy of AMG510 combined with 3-MA in vivo. The results of this study revealed that AMG510 exhibited favorable antitumor activity against KRAS G12C-mutant pancreatic cancer in vitro and in vivo, and the combination of AMG510 and 3-MA may represent a candidate therapeutic regimen for the clinical treatment of KRAS G12C-mutant pancreatic cancer.
Integrative multi-omics and network analysis identify potential targets of Chaihu Shugan Xiaozheng Formula in breast cancer.
Luo T, Xue M, Du Y … +3 more , Chen H, Sun Y, Sun H
Transl Oncol · 2026 Aug · PMID 42184719 · Full text
BACKGROUND: Breast cancer (BC) is linked to emotional stress and neuroendocrine-immune dysregulation. Chaihu Shugan Xiaozheng Formula (CSXF) shows clinical efficacy in BC with depressive symptoms, yet its mechanisms rema...
BACKGROUND: Breast cancer (BC) is linked to emotional stress and neuroendocrine-immune dysregulation. Chaihu Shugan Xiaozheng Formula (CSXF) shows clinical efficacy in BC with depressive symptoms, yet its mechanisms remain unclear. This study aims to investigate the therapeutic effects of CSXF in modulating neuroendocrine-immune networks and tumor-related pathways in BC. METHODS: The bioactive compounds of CSXF were screened using the TCMSP database. Target genes that intersected with differentially expressed genes associated with BC from the TCGA-BRCA dataset were analyzed. Prognostic signatures were constructed through Cox and LASSO regression models. Multi-omics profiling included immune infiltration, pathway enrichment, molecular docking, and RT-qPCR validation in BC tissue samples. RESULTS: Five core targets formed a prognostic model with high predictive accuracy. High-risk patients exhibited elevated mortality independent of age/NM stage. Oxidative phosphorylation activation and myeloid-derived suppressor cell infiltration correlated with CD14 overexpression in high-risk groups. RT-qPCR confirmed tumor-specific downregulation of CD14, PPARG, and CHRM1 in BC tissues. CONCLUSIONS: CSXF treats BC via multi-target modulation of neuroendocrine-immune and tumor pathways, providing prognostic biomarkers and mechanistic insights.
The silent pharmacist: Harnessing the gut microbiome to improve therapy in hematologic malignancies.
El-Sehrawy AAMA, Soleimani Samarkhazan H
Transl Oncol · 2026 Aug · PMID 42184718 · Full text
The gut microbiome, a complex ecosystem of microorganisms, is now recognized as a key determinant of drug efficacy and toxicity, giving rise to the field of pharmacomicrobiomics. This review decodes the profound influenc...
The gut microbiome, a complex ecosystem of microorganisms, is now recognized as a key determinant of drug efficacy and toxicity, giving rise to the field of pharmacomicrobiomics. This review decodes the profound influence of the gut microbiome on treatment outcomes for hematologic malignancies. We explore the tripartite mechanistic pathways through which gut microbes act: the direct enzymatic biotransformation of chemotherapeutic agents, the indirect immunomodulation of systemic and anti-tumor responses, and the preservation of mucosal barrier integrity to prevent devastating complications like graft-versus-host disease (GVHD). The manuscript details how the microbiome interacts with specific drug classes, from conventional chemotherapies like cyclophosphamide to cutting-edge immunotherapies like immune checkpoint inhibitors and CAR-T cells, shaping their clinical success. Furthermore, we discuss the translational potential of targeting this "silent pharmacist" through fecal microbiota transplantation, next-generation probiotics, and dietary interventions. Finally, we highlight the main translational opportunities, current limitations, and future clinical priorities for integrating microbiome science into hematology, paving the way for more personalized and improved cancer care.
Corrigendum to "Sitravatinib combined with venetoclax exerts effective synergy to eliminate acute myeloid leukemia cells with FLT3-ITD mutations" [Translational Oncology 58 (2025) 102467].
Yang J, Zhang Y, Li Q … +1 more , Wang P
Transl Oncol · 2026 Jul · PMID 42178713 · Full text
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Corrigendum to "Circular RNA circAHSA1 Serves as a Stable Serum Biomarker for the Diagnosis and Progression of Gastric Cancer" [Translational Oncology 63 (2026)102620].
He J, Ma S, Kuai S … +1 more , Ju S
Transl Oncol · 2026 Jul · PMID 42178712 · Full text
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Integrated histopathology-transcriptomic biomarker enhances survival prediction in HNSCC patients treated with immunotherapy.
Belete M, Thakkar N, Khatri I … +10 more , Guan M, Sun Y, Muthuswamy A, Kolder I, Si H, Soong D, Higgs BW, Brady LK, Zou J, Sridhar S
Transl Oncol · 2026 Aug · PMID 42176558 · Full text
Recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains a challenging disease with modest response to immune checkpoint inhibitors and a need for more robust predictive biomarkers. In a real-wo...
Recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains a challenging disease with modest response to immune checkpoint inhibitors and a need for more robust predictive biomarkers. In a real-world (RW) cohort of patients treated with pembrolizumab alone or in combination with chemotherapy, we evaluated transcriptomic and histopathologic features associated with therapeutic benefit. PD-L1 expression, measured by combined positive score (CPS), was not significantly associated with progression-free survival (PFS). In contrast, immune-related gene signatures, particularly those linked to T cells and tertiary lymphoid structures (TLS), were predictive of improved outcomes. TLS presence identified from Hematoxylin and Eosin-stained (H&E) whole slide images correlated with favorable survival and showed association with RNA-derived TLS signatures. TLS-associated features demonstrated treatment-specific prognostic patterns, with stronger predictive power in pembrolizumab monotherapy versus combination therapy. We developed multimodal risk prediction models integrating molecular features with imaging data which better associated with RW outcomes. Evaluation using concordance index analysis revealed that traditional pathological markers and individual molecular signatures had modest predictive capability. Digital pathology features achieved better performance than clinical or molecular features alone, but the combination of imaging and molecular features yielded the highest predictive accuracy with concordance index values of 0.86 and 0.81 in pembrolizumab and combination therapy cohorts, respectively. Kaplan-Meier analysis confirmed that our multimodal risk signature achieved significant separation between high- and low-risk groups in both treatment arms, substantially outperforming molecular features alone. These findings highlight that integrating transcriptomic and histopathological data enables precise patient stratification for immunotherapy in R/M HNSCC.
Non-invasive predictive model for incidental gallbladder carcinoma based on multimodal features: Integrating clinical data, MRI radiomics, and deep transfer learning features.
Gao Q, Liu T, Song H … +11 more , Hu Y, Ren S, Li Z, Yang H, Liu L, Chang X, Liu Y, Wang F, Zhao D, Liu X, Wang Z
Transl Oncol · 2026 Aug · PMID 42172792 · Full text
Gallbladder carcinoma, among the most prevalent malignancies of the biliary system, often presents with insidious early symptoms. Delayed diagnosis of incidental gallbladder carcinoma frequently leads to therapeutic dela...
Gallbladder carcinoma, among the most prevalent malignancies of the biliary system, often presents with insidious early symptoms. Delayed diagnosis of incidental gallbladder carcinoma frequently leads to therapeutic delays, significantly compromising patient prognosis. Clinical data,preoperative Magnetic Resonance Imaging examinations, and histopathological records from incidental gallbladder carcinoma patients were retrospectively enrolled. An integrated noninvasive predictive model was developed by combining deep learning features extracted from Magnetic Resonance Imaging radiomics with key clinical predictors. Data from 299 patients with benign gallbladder disease and 106 incidental gallbladder carcinoma cases were analyzed. Multimodal deep learning algorithms identified an optimal predictive model. Multivariate analysis revealed hemoglobin, direct bilirubin, age, distance of the cystic duct from the confluence of right and left hepatic ducts, and diameter of the common bile duct as independent predictors of incidental gallbladder carcinoma (all P<0.01). The multimodal combined feature-based prediction model (AUC=0.894[95%CI 0.829-0.960]) surpassed unimodal models (Clinic:0.862 [ 95%CI 0.787-0.936]; Rad: 0.797 [ 95%CI 0.716-0.878]; DLR: 0.844[ 95%CI 0.775-0.912]) in test cohort. Haemoglobin, direct bilirubin,age, distance of the cystic duct from the confluence of right and left hepatic ducts, and diameter of the common bile duct constitute independent predictors of incidental gallbladder carcinoma. The multimodal combined feature-based prediction model significantly outperforms single-modality models, offering a robust tool for preoperative risk stratification.
Translational issues with phototherapy of cancer.
Ghafarkhani M, Abdollahpour-Alitappeh M, Alizadeh Z … +4 more , Azar ST, Nemati M, Zarebkohan A, Klionsky DJ
Transl Oncol · 2026 Aug · PMID 42172791 · Full text
Cancer is one of the most common and deadly diseases which has challenged human knowledge since its discovery. There are a variety of therapies, such as radiotherapy, chemotherapy, palliative surgery, medicine, and gene...
Cancer is one of the most common and deadly diseases which has challenged human knowledge since its discovery. There are a variety of therapies, such as radiotherapy, chemotherapy, palliative surgery, medicine, and gene therapy, used for patients suffering from cancer, all of which represent, to some extent, a kind of failure. However, a number of novel strategies based on nanotechnology (including, photodynamic therapy [PDT] and photothermal therapy [PTT]) have been introduced in recent years, which appear to have the ability to be used as an auxiliary treatment for chemotherapy and radiotherapy in the future. Interestingly, cancer cells, in response to various therapeutic factors, can utilize certain cellular mechanisms and processes for their survival and growth. For example, macro autophagy/autophagy, can alter the cancer cell fate, from autophagic cell death to dormancy (as a key factor in tumor recurrence). Nonetheless, there have been conflicting conclusions regarding the interactions of phototherapy methods with cells as well as their wanted or unwanted impacts on these cells. In addition, there are complicated and controversial associations among the most common cell death mechanisms such as apoptosis, autophagy, and necrosis as well as tumor treatment and recurrence. The present review aims to describe various responses of cancer cells to photo-based therapy, which can control cell death or dormancy. Moreover, we discuss whether the incorrect application of various phototherapy parameters not only fails to treat and eradicate cancerous tumors, but also mediates the entry of tumor cells into the dormancy phase or even promotes a cancer flare up.
Exploring the role of 4D printing materials, techniques, and characteristics for personalized oncology.
Ashique S, Garg A, Islam A … +6 more , Taj T, Adhikary K, Ghazanfar S, Mojgani N, Hussain S, Taghizadeh-Hesary F
Transl Oncol · 2026 Aug · PMID 42166814 · Full text
Cancer is still a global concern. Cancer management is intricate in all fields, from diagnosing or defining prognosis to selecting appropriate treatment and managing its adverse effects. In recent years, three-dimensiona...
Cancer is still a global concern. Cancer management is intricate in all fields, from diagnosing or defining prognosis to selecting appropriate treatment and managing its adverse effects. In recent years, three-dimensional printing (3DP) innovations have emerged as a ground-breaking technology, offering new possibilities for cancer management. 3DP has advanced further with the addition of a fourth dimension, time, resulting in the concept of four-dimensional printing (4DP), ultimately revolutionizing the approach to cancer management. The 4DP technique has gained attention for its potential applications in cancer therapeutics. It is the next generation of the 3DP technique, which facilitates the advanced fabrication of dynamic constructs. The dynamic nature of 4D materials introduces the element of time, allowing for the observation of temporal changes in cancer behavior and response to therapeutic interventions. The use of 4DP in cancer research holds great promise for advancing our understanding of the disease and improving the translation of preclinical findings to clinical applications. However, 4DP is still in the early stages; thus, research is needed to prove its feasibility in healthcare applications. This review will illustrate the mechanisms used to induce the dynamic constructs of 4DP in cancer management. The recent potential applications of 4DP in cancer therapeutics will be further detailed, and future perspectives and conclusions will finally be proposed.
Molecular profiling and personalized medicine within EURACAN in the SPECTA Arcagen study in comparison to the France Genomic Medicine 2025 Plan in the AURAGEN platform in peritoneal mesotheliomas.
Momenkhan S, Morfouace M, Kepenekian V … +9 more , Glehen O, Villeneuve L, Oliveira J, Tejpar S, Isaac S, Fontaine J, Blay JY, Péron J, Benzerdjeb N
Transl Oncol · 2026 Jul · PMID 42150333 · Full text
Peritoneal mesothelioma (PM) is a rare aggressive cancer with limited therapeutic options upon progression. Two genomic profiling initiatives were launched to implement personalized medicine in rare cancers: the EURACAN...
Peritoneal mesothelioma (PM) is a rare aggressive cancer with limited therapeutic options upon progression. Two genomic profiling initiatives were launched to implement personalized medicine in rare cancers: the EURACAN molecular profiling and personalized medicine pathway and the France Genomic Medicine 2025 plan (AURAGEN). The aim of this study was to describe initial findings in PM and to compare these approaches in a real-world implementation setting. Herein, we present the results from a cohort of 56 patients with PM. Females represented 55.4% of patients; mean age was 55.9 years. The European (Arcagen) study profiled 26 patients and the AURAGEN platform profiled 42 patients. Genomic sequencing was performed using Foundation Medicine for the Arcagen cohort and whole-genome sequencing (WGS) for the AURAGEN cohort. Arcagen used FFPE tissue or blood depending on material availability, whereas AURAGEN relied on fresh frozen tumor tissue with paired blood (and RNA sequencing when feasible). Both cohorts displayed a predominance of alterations in BAP1, NF2, and CDKN2A/B. One patient with an ALK::STRN fusion was treated with Alectinib. AURAGEN identified a larger number of altered genes overall, while the proportion of therapeutic targets was similar between approaches. In conclusion, comprehensive molecular profiling offers potential therapeutic strategies for PM patients. Panel-based profiling and pan-genomic WGS appear complementary in real-world practice, each with distinct strengths and limitations.
The Sig27 multigene stratifies breast cancer fatality risk via reflecting tumor-associated immune suppressive features.
Su Y, Dong Y, Zhang T … +1 more , Tang D
Transl Oncol · 2026 Jul · PMID 42150332 · Full text
We evaluated the biomarker potential of Sig27, a 27-gene panel originating from prostate cancer, in breast cancer (BC). Orthotopic BC tumors were generated in Balb/c mice using 4T1 cells expressing either empty vector (E...
We evaluated the biomarker potential of Sig27, a 27-gene panel originating from prostate cancer, in breast cancer (BC). Orthotopic BC tumors were generated in Balb/c mice using 4T1 cells expressing either empty vector (EV) or the gain-of-function PCSK9 mutant D374Y. Sig27 expression was analyzed in mouse tumors, 13,103 primary BCs, 60 metastases, and 780 normal breast tissues. Its prognostic value was assessed in BC, 20 other cancer types, and in tumor-associated macrophages (TAMs), regulatory T cells (Tregs), and exhausted CD8⁺ T cells (CD8Tex). Sig27 was significantly altered in D374Y vs. EV tumors and showed consistent dysregulation in primary and metastatic BCs. It stratified BC fatality risk comparably to OncotypeDX and MammaPrint. Notably, Sig27 predicted poor prognosis across 21 cancer types. In 2716 BCs, OncotypeDX and MammaPrint correlated with mitotic progression, while Sig27 was predominantly associated with immune regulation. In bulk RNA-seq datasets (n = 6734), Sig27 and its key genes (FPR3, LAMP3, and FAM65B) were strongly associated with multiple immune checkpoints (ICs). Single-cell RNA-seq data revealed their primary expression in TAMs, and to a lesser extent in Tregs and CD8Tex. These associations were enhanced in Sig27IM, formed by FPR3, LAMP3, and FAM65B. Their expression, along with Pd-l1, Lgals9, and Pvrig, was upregulated in D374Y tumors. Furthermore, Sig27 and Sig27IM predicted pathologic complete response in BC treated with PD1 and PD-L1 inhibitors; Sig27IM displayed robust correlations with established immune-signatures: CTL, Merck18, TIDE, and STAT1_sig. Collectively, Sig27 captures BC's immune properties, which likely contribute to its biomarker potential.
Combination of APS, HMGN1, and anti-TNFR2 antibody remodels the tumor immune microenvironment to enhance antitumor immunity in colorectal cancer.
Zhao L, Pei X, Wu H … +6 more , Zhou S, Song J, Wan Q, Lv H, Xu J, Nie Y
Transl Oncol · 2026 Jul · PMID 42150331 · Full text
Astragalus polysaccharide (APS), a major bioactive component of Astragalus membranaceus, has shown antitumor potential through modulation of the tumor microenvironment (TME) and immune responses. High mobility group nucl...
Astragalus polysaccharide (APS), a major bioactive component of Astragalus membranaceus, has shown antitumor potential through modulation of the tumor microenvironment (TME) and immune responses. High mobility group nucleosome binding domain 1 (HMGN1), a natural agonist of TLR4, promotes dendritic cell (DC) maturation, whereas an anti-TNFR2 antibody relieves immunosuppression by targeting regulatory T cells (Tregs). Although immunotherapy holds promise for the treatment of colorectal cancer (CRC), more effective combination strategies are still needed. Here, we investigated the therapeutic efficacy of APS in combination with HMGN1 and an anti-TNFR2 antibody in a murine CRC model. This triple combination regimen eradicated CT26 tumors and induced durable, tumor specific immune memory. Mechanistic analyses showed that the treatment activated DCs in vitro and induced profound remodeling of the TME in vivo, including increased CD8 T cell infiltration and reduced Treg abundance. The therapy was also associated with altered cytokine production profiles and downregulation of Tim-3, a marker of T-cell exhaustion. These findings indicate that APS combined with HMGN1 and an anti-TNFR2 antibody exerts a synergistic antitumor effect by simultaneously enhancing antigen presentation, relieving immunosuppression, and restoring T-cell function. In conclusion, this therapeutic approach holds promise as a novel and effective treatment strategy for CRC.
Concurrent immunoradiotherapy with Toripalimab versus concurrent chemoradiotherapy with S-1 in older patients with esophageal squamous cell carcinoma: a retrospective cohort study.
Huang Y, Zhou C, Zhu J … +4 more , Jia H, Zhao F, Yang H, Zhou S
Transl Oncol · 2026 Jul · PMID 42143854 · Full text
INTRODUCTION: Evidence for concurrent immunoradiotherapy (CIRT) in older patients with esophageal squamous cell carcinoma (ESCC) is limited, whereas S-1-based concurrent chemoradiotherapy (CCRT) has shown benefits. METHO...
INTRODUCTION: Evidence for concurrent immunoradiotherapy (CIRT) in older patients with esophageal squamous cell carcinoma (ESCC) is limited, whereas S-1-based concurrent chemoradiotherapy (CCRT) has shown benefits. METHODS: We retrospectively included 47 older patients with ESCC treated with CIRT (n = 22) or CCRT (n = 25). Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were analyzed. Absolute lymphocyte count (ALC), pan-immune-inflammation value (PIV), platelet lymphocyte ratio (PLR), lymphocyte monocyte ratio (LMR), neutrophil lymphocyte ratio (NLR), and systemic inflammation response index (SIRI) were collected at four timepoints (pre-, during1-, during2-, post-) and explored using univariate and multivariate Cox models. RESULTS: Objective response rate and disease control rate were 77.3% and 90.9% with CIRT, and 100% with CCRT. Median PFS (9.67 vs 20.63 months; P = 0.042) and OS (13.67 vs 23.73 months; P = 0.045) were shorter with CIRT. Grade ≥ 3 AEs occurred in 72.7% (CIRT) and 96.0% (CCRT). Distant recurrence predominated with CIRT (66.7% of recurrences), while regional/local relapse was more common with CCRT (50.0%). ALC and LMR declined during therapy and partially recovered after treatment; PIV, PLR, NLR, and SIRI showed inverse dynamics. Treatment group, during1-ALC, and pre-SIRI were independent prognostic factors for OS. Patients receiving CIRT with low during1-ALC, high pre-SIRI/PIV, or high during1-PLR/NLR had the worst OS. CONCLUSIONS: CIRT was tolerable in older patients with ESCC but associated with inferior outcomes, though confounding cannot be excluded. Our analysis indicated a potential correlation between lymphocyte/monocyte dynamics and response, suggesting lymphopenia mitigation could improve efficacy.
A RIPK2 activity signature in prostate cancer: Modulation by RIPK2 inhibition and clinical association.
Elgehama AM, Yang Q, Pires Sanches JG … +4 more , He Z, Ruegg L, You S, Yang W
Transl Oncol · 2026 Jul · PMID 42143470 · Full text
Receptor-interacting protein kinase 2 (RIPK2) has emerged as a promising therapeutic target in multiple malignancies, including prostate cancer (PC). However, the lack of reliable biomarkers to assess RIPK2 activity limi...
Receptor-interacting protein kinase 2 (RIPK2) has emerged as a promising therapeutic target in multiple malignancies, including prostate cancer (PC). However, the lack of reliable biomarkers to assess RIPK2 activity limits patient selection and pharmacodynamic evaluation in anti-RIPK2 therapeutic strategies. To address this need, we performed RNA sequencing of three PC cell lines (22Rv1, DU145, and PC3) with CRISPR/Cas9-mediated RIPK2 knockout using two independent guide RNAs. This analysis identified 13 candidate RIPK2-regulated genes, eight of which were validated by reverse transcription quantitative PCR and incorporated into a RIPK2 activity signature. Pharmacological inhibition of RIPK2 using two structurally distinct inhibitors significantly reduced RIPK2 signature scores in five independent PC cell lines in a dose- and/or time-dependent manner. Consistently, RIPK2 inhibition progressively suppressed signature scores in vivo, supporting its utility as a pharmacodynamic readout of RIPK2 signaling output. Elevated RIPK2 signature scores were associated with metastatic disease and adverse clinical outcomes and demonstrated stronger clinical associations than RIPK2 mRNA expression alone. Mechanistic analyses identified c-Myc and KDM5A as candidate mediators of RIPK2-dependent regulation of the signature genes. Together, these findings define a RIPK2-regulated gene signature that provides a framework for patient stratification and pharmacodynamic assessment in future RIPK2-targeted clinical studies.
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