Molecular therapy. Oncology最新文献

Erratum: AGTR1 signaling contributes to tumor immunity and therapy response in non-small cell lung cancer. 勘误：AGTR1信号有助于非小细胞肺癌的肿瘤免疫和治疗反应。

IF 5.3

Molecular therapy. Oncology Pub Date : 2026-09-10 eCollection Date: 2026-09-17 DOI: 10.1016/j.omton.2026.201336

Tatsuki Ikoma, Keigo Araki, Mai Kitagawa, Natsuno Makihara, Yutaro Nagata, Kazuki Fujii, Yukiko Okuno, Keisuke Kamisako Yuta Okazaki, Kentaro Nakanishi, Yume Sanada, Kiyori Yoshida, Kahori Nakahama, Yuki Takeyasu, Utae Katsushima, Yuta Yamanaka, Satoshi Ikeda, Hiroshige Yoshioka, Toshio Shimizu, Takayasu Kurata

引用次数: 0

Dual targeting of PDPN and GD2 enhances CAR T cell efficacy against glioblastoma and promotes durable tumor control. PDPN和GD2的双重靶向增强了CAR - T细胞对胶质母细胞瘤的疗效，促进了肿瘤的持久控制。

IF 5.3

Molecular therapy. Oncology Pub Date : 2026-09-04 eCollection Date: 2026-09-17 DOI: 10.1016/j.omton.2026.201318

Julian Hübner, Thomas Nerreter

引用次数: 0

Precision medicine meets artificial intelligence: A new prognostic model for lower-grade glioma. 精准医疗与人工智能的结合：低级别胶质瘤的新预后模型。

IF 5.3

Molecular therapy. Oncology Pub Date : 2026-09-01 eCollection Date: 2026-09-17 DOI: 10.1016/j.omton.2026.201330

Mohamed A Hammad, Hossam M Ashour

引用次数: 0

Pediatric cancer immunotherapy: The moment has arrived. 儿童癌症免疫治疗：时机已经到来。

IF 5.3

Molecular therapy. Oncology Pub Date : 2026-09-01 eCollection Date: 2026-09-17 DOI: 10.1016/j.omton.2026.201256

Nirali N Shah

引用次数: 0

Reversal of repeated red cards reprieves RP-1. 重复红牌的反转可以缓解RP-1。

IF 5.3

Molecular therapy. Oncology Pub Date : 2026-08-28 eCollection Date: 2026-09-17 DOI: 10.1016/j.omton.2026.201327

Richard G Vile

引用次数: 0

A p53^R273H-selective bispecific T cell engager: Computational design and functional validation. p53r273h选择性双特异性T细胞参与器：计算设计和功能验证。

IF 5.3

Molecular therapy. Oncology Pub Date : 2026-08-26 eCollection Date: 2026-09-17 DOI: 10.1016/j.omton.2026.201333

Nhan Huynh, Thu-My Thi Nguyen, Ngoc Thi Bui, Thao-Nguyen Ho Nguyen, Diem Tp Tran, Hoai-Nghia Nguyen, Cuong Thach Nguyen

{"title":"A p53R273H-selective bispecific T cell engager: Computational design and functional validation.","authors":"Nhan Huynh, Thu-My Thi Nguyen, Ngoc Thi Bui, Thao-Nguyen Ho Nguyen, Diem Tp Tran, Hoai-Nghia Nguyen, Cuong Thach Nguyen","doi":"10.1016/j.omton.2026.201333","DOIUrl":"10.1016/j.omton.2026.201333","url":null,"abstract":"TP53 mutations occur in over 50% of human cancers and generate shared neoantigens, including p53R273H, which represents a compelling target for precision immunotherapy. However, HLA allele-specific presentation and the risk of off-target toxicity remain major challenges. Here, we developed a group of bispecific T cell engagers (TCEs), namely, TCE01 and its optimized versions, based on a stimulated patient-derived TCR that specifically recognizes p53R273H presented by HLA-C∗01:02. The immunodominant 9-mer epitope SFEVHVCAC was identified as selectively presented by this allele. Incorporation of the stapled single-chain TCE formats reduced molecular weight by ∼24% compared with full-length constructs, while fully preserving binding affinity and markedly enhancing in vitro T cell activation and cytotoxicity (>90% at 0.625 nM). Machine learning-guided directed evolution using Boltz-2 and EvotProtGrad yielded TCE01Cr3, exhibiting a K d of 2.51 nM and a subpicomolar EC50. Alanine scanning combined with combinatorial peptide library screening and structural modeling pinpointed peptide residues 2 and 4 as critical for TCR recognition in context of TCE01. TCE01Cr3 exhibited remarkable in vitro functional stability following 128 h of incubation in human serum and demonstrated a prolonged in vivo half-life in mice (t 1/2 = 39.40 ± 10.50 h). In 3D model, monotherapy with TCE01Cr3 eliminated >80% of p53R273H-expressing colorectal cancer cells within 48 h while sparing non-malignant stroma, independent of chemotherapy potentiation (oxaliplatin or irinotecan). This off-the-shelf TCE provides a framework for precision immunotherapy in HLA-C∗01:02-positive patients with p53R273H tumors.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"34 3","pages":"201333"},"PeriodicalIF":5.3,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993593","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}

引用次数: 0

Comprehensive preclinical evaluation of second-generation miRNA-regulated Coxsackievirus B3-BHP: Potent antitumor efficacy and safety. 第二代mirna调控柯萨奇病毒B3-BHP的临床前综合评价：有效的抗肿瘤疗效和安全性。

IF 5.3

Molecular therapy. Oncology Pub Date : 2026-08-21 eCollection Date: 2026-09-17 DOI: 10.1016/j.omton.2026.201332

Yuki Sakashita, Shohei Miyamoto, Miyako Sagara, Shun Ito, Yukiko Kobayashi, Yoshio Momoda, Fumiaki Yano, Ken Eto, Kenzaburo Tani, Mutsunori Murahashi

{"title":"Comprehensive preclinical evaluation of second-generation miRNA-regulated Coxsackievirus B3-BHP: Potent antitumor efficacy and safety.","authors":"Yuki Sakashita, Shohei Miyamoto, Miyako Sagara, Shun Ito, Yukiko Kobayashi, Yoshio Momoda, Fumiaki Yano, Ken Eto, Kenzaburo Tani, Mutsunori Murahashi","doi":"10.1016/j.omton.2026.201332","DOIUrl":"10.1016/j.omton.2026.201332","url":null,"abstract":"Oncolytic virotherapy employing Coxsackievirus B3 has emerged as a promising and innovative strategy for cancer treatment. However, wild-type Coxsackievirus B3 is associated with significant organ toxicities, such as viral hepatitis, myocarditis, and pancreatitis, which have presented major obstacles to its clinical application. In this study, we engineered a second-generation recombinant Coxsackievirus B3 (CVB3-BHP) by incorporating target sequences for the pancreas-specific miR-217 and the miR-34a, which is predominantly expressed in normal tissues, to further enhance its safety profile. Preclinical evaluation demonstrated that CVB3-BHP exhibited potent and dose-dependent antitumor efficacy in murine tumor models, with complete tumor regression or marked shrinkage observed in the high-dose group. Biodistribution analysis showed that CVB3-BHP transiently accumulated in the spleen and lacrimal gland but was rapidly cleared from these tissues over time, with limited excretion in urine and feces. Toxicity assessment indicated that even repeated high-dose administration did not induce overt systemic toxicity or organ damage. Although mild inflammation and acinar atrophy were observed in the lacrimal gland, no clinically significant adverse events were observed. Collectively, these findings indicate that CVB3-BHP combines robust antitumor efficacy with an improved safety profile, supporting its potential as a strong candidate for clinical translation in oncolytic virotherapy.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"34 3","pages":"201332"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964171","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}

引用次数: 0

Targeting LKB1-inactivated lung cancers with a stapled peptide inhibitor of the CRTC-CREB pathway. CRTC-CREB通路的钉接肽抑制剂靶向lkb1失活肺癌

IF 5.3

Molecular therapy. Oncology Pub Date : 2026-08-21 eCollection Date: 2026-09-17 DOI: 10.1016/j.omton.2026.201331

Xin Zhou, Gregory H Bird, Mu Yu, Jian-Liang Li, Xzaviar K Solone, Michael C Chung, Juan Guan, Loren D Walensky, Lizi Wu

{"title":"Targeting LKB1-inactivated lung cancers with a stapled peptide inhibitor of the CRTC-CREB pathway.","authors":"Xin Zhou, Gregory H Bird, Mu Yu, Jian-Liang Li, Xzaviar K Solone, Michael C Chung, Juan Guan, Loren D Walensky, Lizi Wu","doi":"10.1016/j.omton.2026.201331","DOIUrl":"10.1016/j.omton.2026.201331","url":null,"abstract":"Non-small cell lung cancers (NSCLCs) with inactivation of the tumor suppressor LKB1 are common and respond poorly to current therapies. We previously identified aberrant activation of the CRTC-CREB transcriptional pathway as a key driver of malignancy in LKB1-deficient lung cancer. In this study, we developed stabilized α-helical peptides, termed stabilized alpha helices of the CREB binding domain (SAH-CBDs), which were designed to disrupt the CRTC-CREB protein-protein interaction. SAH-CBD peptides adopt a stable, bioactive α-helical conformation, bind directly to CREB, and effectively block CRTC-CREB complex formation in vitro. Importantly, SAH-CBDs penetrate cells without causing membrane disruption, inhibit CREB-dependent transcription, and selectively suppress the growth of LKB1-null lung cancer cells, with minimal effects on LKB1-wild-type cells. These findings establish SAH-CBDs as a mechanistic tool and a prototype therapeutic for targeting a key transcriptional vulnerability in LKB1-inactivated NSCLC.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"34 3","pages":"201331"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964134","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}

引用次数: 0

USP15 regulates mitotic fidelity, metastatic potential, and chemotherapeutic response in ovarian cancer cells. USP15调节卵巢癌细胞的有丝分裂保真度、转移潜能和化疗反应。

IF 5.3

Molecular therapy. Oncology Pub Date : 2026-08-20 eCollection Date: 2026-09-17 DOI: 10.1016/j.omton.2026.201329

Ayokunnumi Ogunsanya, Fatimah Alfaran, Omuya Noel Amadu, Achuth Padmanabhan

{"title":"USP15 regulates mitotic fidelity, metastatic potential, and chemotherapeutic response in ovarian cancer cells.","authors":"Ayokunnumi Ogunsanya, Fatimah Alfaran, Omuya Noel Amadu, Achuth Padmanabhan","doi":"10.1016/j.omton.2026.201329","DOIUrl":"10.1016/j.omton.2026.201329","url":null,"abstract":"Aggressive metastasis and chemoresistance are underlying cause for the poor clinical outcome in ovarian cancer patients. Identifying factors that drive these phenotypes is critical in developing effective therapeutic strategies for metastatic ovarian cancer. In this report, we show that the deubiquitinase USP15 is a critical regulator of ovarian cancer cell proliferation, metastasis, and drug resistance. USP15 levels are elevated in metastatic ovarian tumors and are associated with poor clinical outcome in patients. Depletion and inhibition of USP15 dramatically reduces cell viability and proliferation in a broad spectrum of ovarian cancer cells. Mechanistically, USP15 knockdown disrupts chromosomal segregation, leading to DNA damage, micronuclei formation, and mitotic catastrophe. This causes ovarian cancer cells to undergo cell-cycle arrest at the G2-M checkpoint. Further, USP15 knockdown decreases the metastatic potential of ovarian cancer cells in vitro, reduces tumor burden, and extends survival in mouse xenograft models. Consistent with its role in maintaining mitotic fidelity, USP15 depletion sensitizes ovarian cancer cells to mitotic inhibitors and DNA damage inducing chemotherapeutics. Collectively, these findings establish USP15 as a key driver of ovarian cancer metastasis and highlight its potential as an actionable therapeutic target to improve the effectiveness of extant chemotherapeutic agents.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"34 3","pages":"201329"},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964121","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}

引用次数: 0

Additive effect of Ruta graveolens bioactive phytoconstituents and cisplatin through PKC/MEK/ERK pathway in glioblastoma. 芦花生物活性成分与顺铂在胶质母细胞瘤中PKC/MEK/ERK通路的叠加作用。

IF 5.3

Molecular therapy. Oncology Pub Date : 2026-08-12 eCollection Date: 2026-09-17 DOI: 10.1016/j.omton.2026.201320

Grazia Romano, Valentina Morgera, Antonio Pezone, Samantha Messina, Paolo Rosa, Manuela Iovinella, Claudia Ciniglia, Maria Teresa Gentile, Antonio Porcellini, Antonia Feola

{"title":"Additive effect of Ruta graveolens bioactive phytoconstituents and cisplatin through PKC/MEK/ERK pathway in glioblastoma.","authors":"Grazia Romano, Valentina Morgera, Antonio Pezone, Samantha Messina, Paolo Rosa, Manuela Iovinella, Claudia Ciniglia, Maria Teresa Gentile, Antonio Porcellini, Antonia Feola","doi":"10.1016/j.omton.2026.201320","DOIUrl":"10.1016/j.omton.2026.201320","url":null,"abstract":"Glioblastoma multiforme (GBM) is a lethal malignancy with limited therapeutic options. Its aggressive progression and resistance to standard therapy necessitate the development of novel therapeutic strategies. Plant-based compounds have emerged as promising candidates for therapeutic development modulating key targets in cancer. The Ruta graveolens displays anti-inflammatory, analgesic, and antimicrobial properties. Herein, we report the anticancer potential of R. graveolens water extract (RGWE) on long-term cultures of human glioblastoma and elucidate the regulatory mechanisms driving its effect. Secondary stabilized cell cultures (U-87 MG, T98MG, and U-138 MG) and primary cell culture (FCN, MZC, and GL18-15) were either treated with RGWE and/or cis-diamminedichloroplatinum (cisplatin, CDDP). Cytostatic responses were assessed by cell viability (TB exclusion test), cell cycle (propidium iodide [PI] staining), and apoptosis (Annex-V and caspase-3) assays. We demonstrate that RGWE slows U-87 MG growth without affecting apoptosis and arrests the cell cycle in the G2/M phase. Mechanistically, RGWE interferes with PKC/MEK/ERK signaling pathway, as assessed by western blot analysis, through PKC inhibition in its active form. Furthermore, the combination of RGWE and cisplatin enables the use of a sublethal dose of the latter (0.2 μg/mL), thereby reducing cytotoxicity and the resistance to the drug. These findings reveal a novel mechanism by which RGWE controls glioblastoma growth, highlighting the therapeutic potential of targeting the PKC/MEK/ERK axis in glioma treatment.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"34 3","pages":"201320"},"PeriodicalIF":5.3,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13524684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148858029","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}

引用次数: 0