tbuckley/cabot-search huggingface dataset:
Correction: LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer
Authors: Yun Wang, Jia-Huan Lu, Qi-Nian Wu, Ying Jin, De-Shen Wang, Yan-Xing Chen, Jia Liu, Xiao-Jing Luo, Qi Meng, Heng-Ying Pu, Ying-Nan Wang, Pei-Shan Hu, Ze-Xian Liu, Zhao-Lei Zeng, Qi Zhao, Rong Deng, Xiao-Feng Zhu, Huai-Qiang Ju, Rui-Hua Xu
Journal: Molecular Cancer (2025)
Second-generation anti-amyloid monoclonal antibodies for Alzheimer’s disease: current landscape and future perspectives
Authors: Byeong-Hyeon Kim, Sujin Kim, Yunkwon Nam, Yong Ho Park, Seong Min Shin, Minho Moon
Journal: Translational Neurodegeneration (2025)

Abstract Alzheimer’s disease (AD) is the most common type of dementia. Monoclonal antibodies (MABs) serve as a promising therapeutic approach for AD by selectively targeting key pathogenic factors, such as amyloid-β (Aβ) peptide, tau protein, and neuroinflammation. Specifically, based on their efficacy in removing Aβ plaques from the brains of patients with AD, the U.S. Food and Drug Administration has approved three anti-amyloid MABs, aducanumab (Aduhelm®), lecanemab (Leqembi®), and donanemab (Kisunla™). Notably, lecanemab received traditional approval after demonstrating clinical benefit, supporting the Aβ cascade hypothesis. These MABs targeting Aβ are categorized based on their affinity to diverse conformational features of Aβ, including monomer, fibril, protofibril, and plaque forms of Aβ as well as pyroglutamate Aβ. First-generation MABs targeting the non-toxic monomeric Aβ, such as solanezumab, bapineuzumab, and crenezumab, failed to demonstrate clinical benefit for AD in clinical trials. In contrast, second-generation MABs, including aducanumab, lecanemab, donanemab, and gantenerumab directed against pathogenic Aβ species and aggregates have shown that reducing Aβ deposition can be an effective strategy to slow cognitive impairment in AD. In this review, we provide a comprehensive overview of the current status, mechanisms, outcomes, and limitations of second-generation MABs for the clinical treatment of AD. Moreover, we discuss the perspectives and future directions of anti-amyloid MABs in the treatment of AD.
Acute respiratory distress syndrome (ARDS): from mechanistic insights to therapeutic strategies
Authors: Rongli Xie, Dan Tan, Boke Liu, Guohui Xiao, Fangchen Gong, Qiyao Zhang, Lei Qi, Sisi Zheng, Yuanyang Yuan, Zhitao Yang, Ying Chen, Jian Fei, Dan Xu
Journal: MedComm (2025)

Abstract Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute hypoxic respiratory failure caused by diffuse lung inflammation and edema. ARDS can be precipitated by intrapulmonary factors or extrapulmonary factors, which can lead to severe hypoxemia. Patients suffering from ARDS have high mortality rates, including a 28‐day mortality rate of 34.8% and an overall in‐hospital mortality rate of 40.0%. The pathophysiology of ARDS is complex and involves the activation and dysregulation of multiple overlapping and interacting pathways of systemic inflammation and coagulation, including the respiratory system, circulatory system, and immune system. In general, the treatment of inflammatory injuries is a coordinated process that involves the downregulation of proinflammatory pathways and the upregulation of anti‐inflammatory pathways. Given the complexity of the underlying disease, treatment needs to be tailored to the problem. Hence, we discuss the pathogenesis and treatment methods of affected organs, including 2019 coronavirus disease (COVID‐19)‐related pneumonia, drowning, trauma, blood transfusion, severe acute pancreatitis, and sepsis. This review is intended to provide a new perspective concerning ARDS and offer novel insight into future therapeutic interventions.
Airway stenosis: classification, pathogenesis, and clinical management
Authors: Pengwei Zhao, Zheng Jiang, Xuexin Li, Mailudan Ainiwaer, Leyu Li, Dejuan Wang, Lixiao Fan, Fei Chen, Jun Liu
Journal: MedComm (2025)

Abstract Airway stenosis (AS) is a fibroinflammatory disease characterized by abnormal activation of fibroblasts and excessive synthesis of extracellular matrix, which has puzzled many doctors despite its relatively low prevalence. Traditional treatment such as endoscopic surgery, open surgery, and adjuvant therapy have many disadvantages and are limited in the treatment of patients with recurrent AS. Therefore, it is urgent to reveal the pathogenesis of AS and accelerate its clinical transformation. Based on the discovered pathogenesis, including fibrosis, inflammation, epithelial–mesenchymal transition, metabolic reprogramming, microbiome, genetic susceptibility, and other mechanisms, researchers have developed a series of treatments, such as drug therapy, gene therapy, stem cell therapy, growth factor therapy, protein therapy, and photodynamic therapy. This review introduces the classification of AS, explores the existing pathogenesis and preclinical treatments developed based on the pathogenesis, and finally summarizes the current clinical management. In addition, the prospect of exploring the interaction between different types of cells and between microorganisms and cells to identify the intersection of multiple mechanisms based on single‐cell RNA sequencing, 16S rRNA gene sequencing and shotgun metagenomic sequencing is worth looking forward to.
Plasma membrane-coated nanoparticles and membrane vesicles to orchestrate multimodal antitumor immunity
Authors: Yusuke Ito, Hitomi Kasuya, Mirei Kataoka, Noriko Nakamura, Toshiaki Yoshikawa, Takahiro Nakashima, Haosong Zhang, Yang Li, Tetsuya Matsukawa, Satoshi Inoue, Chitose Oneyama, Seiichi Ohta, Yuki Kagoya
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background A number of immunotherapeutic approaches have been developed and are entering the clinic. Bispecific antibodies (BsAbs) are one of these modalities and induce robust efficacy by endogenous T cells in several hematological malignancies. However, most of the treated patients experience only a temporary benefit. Currently available BsAbs provide only anti-CD3 antibody-mediated T-cell stimulation, but not the costimulation or cytokine signaling essential for full T-cell activation. Here, we hypothesized that the simultaneous input of more comprehensive signals would elicit more robust and durable effector T-cell functions. Methods We genetically engineered the leukemia cell line K562 to express BsAbs, costimulatory ligands, cytokines, and blocking antibodies against immune checkpoint molecules on the cell surface, from which we obtained plasma membrane fractions by mechanical homogenization and subsequent isolation steps. Plasma membranes were reconstituted on the poly (lactic-co-glycolic acid) surface to generate membrane-coated nanoparticles (NPs). Alternatively, nano-sized membrane vesicles (MVs) were generated by ultrasonic dispersion of the isolated membranes. The antitumor function of NPs and MVs loaded with various immunomodulatory factors was evaluated in vitro and in vivo. Results Both membrane-coated NPs and MVs induced BsAb-mediated antigen-specific cytotoxic activity in non-specific T cells, with MVs inducing a slightly better response in vivo. Importantly, T-cell activation was elicited only in the presence of target tumor cells, providing a safety advantage for clinical use. NPs and MVs expressing costimulatory molecules (CD80/4-1BBL) and cytokines (interleukin (IL)-7/IL-15) further enhanced effector T-cell function and induced therapeutic efficacy in vivo. In addition, MVs expressing immune checkpoint antibodies and inflammatory cytokines IL-12 and IL-18 induced objective antitumor responses in solid tumor models partly by converting immunosuppressive macrophages to proinflammatory phenotypes and inducing cytotoxic T-cell infiltration into the tumor. Finally, we showed that MVs were also engineered to activate natural killer (NK) cells by loading multiple ligands. MVs loaded with BsAbs, 4-1BBL, IL-15, and IL-21 induced NK-cell cytotoxic activity in an antigen-specific manner. Conclusions We developed antitumor NPs and MVs that efficiently induced antitumor immune responses in vivo by simultaneously delivering multiple immunostimulatory signals to endogenous T cells. This platform enables the delivery of desired combinations of antitumor immune signals into T cells and NK cells.
Abstract A006: Using ChatGPT to solve clinical radiobiology problems
Authors: Yung-Shuo Kao, Che-Wei Su, Kun-Yao Dai
Journal: Clinical Cancer Research (2025)

Abstract ChatGPT is a powerful large language model and has been applied to many fields in medicine. Radiobiology is the key in the determining of radiation dose in radiation oncology. We would like to test the efficacy of using ChatGPT in clinical radiobiology. A set of 30 clinical radiobiology questions were used in this study. OpenAI API was used to query GPT-4O and generate corresponding answers (Access Date: 2024/6/26). Five different prompts (involving role-playing, role-playing with in-context learning, chain of thought, chain of thought with in-context training, and in-context training) and no prompt were used to test the ability of the model. Questions were further divided into two subgroups, 15 questions without alpha-beta ratio and 15 questions with alpha-beta ratio(s). Answers were graded using the below grading system: Grade 1: totally incorrect; Grade 2: partially correct (either answer or calculation process is correct); Grade 3: totally correct (both answer and calculation process are correct). The chi-square test was used to compare results between different situations. R studio and R language were used in the statistical analysis; p &amp;lt;0.05 is set as statistically significant. The detailed results for each prompt are shown below: No prompt(grade 1: 9, grade 2: 3, grade 3: 18), role-playing (grade 1: 7, grade 2: 6, grade 3: 17), role-playing with in-context learning(grade 1: 10, grade 2: 7, grade 3: 13), chain of thought(grade 1: 10, grade 2: 5, grade 3: 15), chain of thought with in-context learning(grade 1: 11, grade 2: 2, grade 3: 17), and in-context learning(grade 1: 10, grade 2: 4, grade 3: 16). For grade 1 versus grade 2-3, Chi-square test showed p-value = 0.6708, and for grade 1-2 versus grade 3, chi-square test showed p-value = 0.829. That meant that the performances were similar regardless of the prompt. The detailed results for two question types are shown below: questions without alpha-beta ratio (grade 1: 53, grade 2: 10, grade 3: 27), questions with alpha-beta ratio(s) (grade 1: 4, grade 2: 17, grade 3: 69). For grade 1 versus grade 2-3, Chi-square test showed p-value &amp;lt;0.01, and for grade 1-2 versus grade 3, chi-square test showed p-value &amp;lt;0.01. That meant that the performances were different between question with and without alpha-beta ratio(s). In conclusion, without prompting, ChatGPT can correct about 60% of questions. Using different prompts cannot enhance performance. ChatGPT can perform well in questions with alpha-beta ratio(s). Citation Format: Yung-Shuo Kao, Che-Wei Su, Kun-Yao Dai. Using ChatGPT to solve clinical radiobiology problems. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A006.
Abstract B004: TIGIT blockade synergizes with PD-1 blockade and radiation therapy to enhance antitumor T-cell responses in breast cancer
Authors: Seongmin Kim, Seung Hyuck Jeon, Yoomin Kim, Nawon Park, In Ah Kim
Journal: Clinical Cancer Research (2025)

Abstract Background: The study aims to investigate the role of TIGIT in immunosuppressive environment and evaluates the potential of TIGIT blockade (αTIGIT) to improve antitumor immune responses. Methods: We analyzed public transcriptomic data to identify the expression patterns of TIGIT on T cells in breast cancer and its prognostic impact. In addition, a murine TNBC model was utilized to evaluate the effects of PD-1 blockade (αPD-1), local RT, and αTIGIT. T cells in tumors, tumor-draining lymph nodes (TdLNs), and the spleen were analyzed to assess the antitumor immune responses upon the treatments. Results: The analysis revealed that TIGIT is predominantly expressed on T cells within breast cancer, and the expression of TIGIT was associated with poor outcomes in TNBC patients. In the murine model, the combination of αPD-1 and RT increased TIGIT+CD226+CD8+ TILs, which are crucial for the efficacy of αTIGIT. Adding αTIGIT to αPD-1 and RT (αPD-1/RT) resulted in a synergistic antitumor effect, characterized by increased infiltration of CD8+ TILs in both irradiated and nonirradiated tumors. The triple combination therapy (TCT) also resulted in a less exhausted phenotype among CD8+ TILs and increased the proliferation of splenic CD8+ T cells. Moreover, αTIGIT significantly reduced Tregs in tumors, TdLNs, and the spleen when combined with αPD-1/RT. Conclusion: αTIGIT exhibits synergistic effects when added to αPD-1/RT by increasing the infiltration and activation of CD8+ TILs while reducing Tregs. The study suggests that αTIGIT could be an effective strategy to enhance the antitumor efficacy of αPD-1 and RT in TNBC. Citation Format: Seongmin Kim, Seung Hyuck Jeon, Yoomin Kim, Nawon Park, In Ah Kim. TIGIT blockade synergizes with PD-1 blockade and radiation therapy to enhance antitumor T-cell responses in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B004.
Abstract A011: Activity of antibody-drug conjugates with radiation in preclinical bladder cancer models
Authors: Yuzhen Zhou, Surish Shanmugam, Vincent D'Andrea, Isabella Stelter, Dag Stormoen, Rea Chroneos, Timothy Hanlon, Ilana Epstein, Raie Bekele, William Anderson, Zoltan Szallasi, Joaquim Bellmunt, Kent Mouw
Journal: Clinical Cancer Research (2025)

Abstract Antibody-drug conjugates (ADCs) are transforming the treatment landscape in metastatic bladder cancer, but the role of ADCs in localized disease is uncertain. Radiation is a central component of trimodality therapy (TMT), a curative-intent treatment approach for muscle-invasive bladder cancer (MIBC) that includes concurrent radiation and cytotoxic chemotherapy. We investigated the safety and efficacy of combining novel ADCs with radiation in preclinical bladder cancer models. We observed additive cytotoxicity in vitro, and the combination of ADCs with conformal fractionated radiation was well-tolerated and resulted in improved tumor control compared to either agent alone in vivo. We also assessed the impact of DNA repair pathway alterations commonly observed in bladder tumors on sensitivity to ADCs alone and in combination with radiation and DNA repair targeted agents. Homologous recombination (HR) deficiency modestly sensitized bladder cancer cells to MMAE, the payload of the ADC enfortumab vedotin (EV), and potently sensitized cells to govitecan, the payload of the ADC sacitumuzab govitecan (SG). Conversely, nucleotide excision repair (NER) deficiency did not sensitize cells to either MMAE or govitecan. The combination of govitecan and PARP inhibition resulted in synergistic cell killing independent of HR or NER status. Together these data provide preclincal support for clinical efforts to combine ADCs with radiation in MIBC and identify rationale combination therapy approaches. Citation Format: Yuzhen Zhou, Surish Shanmugam, Vincent D'Andrea, Isabella Stelter, Dag Stormoen, Rea Chroneos, Timothy Hanlon, Ilana Epstein, Raie Bekele, William Anderson, Zoltan Szallasi, Joaquim Bellmunt, Kent Mouw. Activity of antibody-drug conjugates with radiation in preclinical bladder cancer models. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A011.
Abstract A005: 18F-Fluorthanatrace PARP inhibitor PET tracer: Potential implications for theranostics
Authors: Lilie Lin, Mahmoud Hammad, Franklin Wong, Timothy A. Yap
Journal: Clinical Cancer Research (2025)

Abstract Objective: PARP (poly [ADP-ribose] polymerase) inhibitors are approved for a variety of malignancies including those with a breast, prostate, and ovarian carcinoma, particularly in the setting of a germline or somatic pathogenic BRCA mutation. There is active interest in the development of theranostics including those with a PARP inhibitor backbone. Methods: We evaluate a novel PARP inhibitor (PARPi) PET tracer 18-Fluorine [18F] Fluorthanatrace (FTT). Patients with primary or metastatic solid tumors with measurable disease initiating therapy with a PARP inhibitor monotherapy or in combination with another systemic agent were eligible. Patients underwent 18F-FTT PET/CT prior to initiation of PARPi and a second 18F-FTT PET 2-4 weeks after initiation of a PARP inhibitor. Hematologic toxicity on PARPi monotherapy or combination was assessed using the CTCAEv5.0 criteria. Regions of interest were drawn over the uninvolved bone marrow (usually taken at L3) and normal muscle to obtain the maximum standardized uptake value. Bone marrow to muscle ratio (B/M) was calculated at baseline and on PARPi. Spearman rank correlation coefficient was used. Results: A total of 21 patients were enrolled and underwent 18F-FTT PET. Patients had a median of 0 (range 0-7) prior lines of systemic therapy. The primary disease site included breast (9), ovary (6), primary peritoneal (1), pancreas (1)and other (4). Measurable uptake of 18F-FTT within the tumor and bone marrow was observed in all patients. Median L3 SUVmax at baseline was 4.3 (range 2.1-11.8) vs. 2.33 (range 1.4-2.9) while on PARP inhibitor. Baseline B/M was associated with highest grade hematologic toxicity in patients (n=10) who received talazoparib monotherapy or combination (r=0.65, p=0.042). While B/M was not associated with hematologic toxicity in patients (n=11) who received olaparib monotherapy or combination (r=0.098, p=0.77). Conclusions: 18F-FTT PET can measure target engagement of PARP inhibitors in bone marrow and may have implications for PARP inhibitor-based theranostics and dosing. Results suggest there may be differential impact of different PARPi on bone marrow and should be considered when selecting a backbone for theranostics. Citation Format: Lilie Lin, Mahmoud Hammad, Franklin Wong, Timothy A. Yap. 18F-Fluorthanatrace PARP inhibitor PET tracer: Potential implications for theranostics. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A005.
Abstract A004: Nodal Management in cancer treatment: Synergistic potential of immune checkpoint inhibitors
Authors: Su-Jin Koh
Journal: Clinical Cancer Research (2025)

Abstract Lymph nodes (LNs) are critical components of the immune system, playing an essential role in the regulation of tumor immune surveillance and the progression of metastatic cancer. Recent advancements in immune checkpoint inhibitors (ICIs), including monoclonal antibodies targeting PD-1, PD-L1, and CTLA-4, have revolutionized cancer therapy by enhancing the immune system's ability to recognize and eliminate tumor cells. However, the interaction between immune checkpoint blockade (ICB) and lymphatic tissue, particularly the role of regional lymph nodes in treatment efficacy, remains insufficiently understood. This research explores the potential of combining immune checkpoint therapy with targeted strategies for managing nodal involvement in cancers. We aim to investigate the mechanisms by which tumor-infiltrating lymph nodes may either aid or hinder the response to ICBs, with a focus on the activation of anti-tumor immune responses within the nodal microenvironment. By examining how immune checkpoints impact tumor-associated lymphoid structures, we aim to identify strategies for improving regional lymph node management, including the use of neoadjuvant ICB, lymph node dissection, and lymph node-targeted drug delivery. The findings of this study may provide insights into optimizing immune checkpoint blockade therapies for cancers with extensive nodal metastasis and lead to novel therapeutic approaches that enhance regional immune responses while minimizing adverse effects. Ultimately, this research has the potential to contribute to a more personalized approach to cancer treatment, particularly for patients with advanced or metastatic disease, where nodal involvement is often a critical determinant of prognosis. Citation Format: Su-Jin Koh. Nodal Management in cancer treatment: Synergistic potential of immune checkpoint inhibitors. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A004.
Abstract B012: Interferon- γ is required for immunotherapy induced radiosensitivity in solid tumors
Authors: Annette Wu, Minjeong Kang, Daeyong Lee, Yifan Wang, Kristin M. Huntoon, Betty Y.S. Kim, Wen Jiang
Journal: Clinical Cancer Research (2025)

Abstract Radiation therapy (RT) is the standard of care for many cancer types, however, some solid tumors fail to respond due to factors such as a hypoxic tumor microenvironment (TME). To overcome radioresistance in these solid tumors, clinical trials combining RT with immune checkpoint blockade (ICB) are ongoing, but hindered by a limited understanding of the mechanisms by which immunotherapies enhance RT response. In this study, we use EO771 breast and CT26 colorectal tumor models to investigate how anti PD-1 therapy improves radiosensitivity to varying RT regimens including single or multiple RT doses administered concurrently or sequentially. We show that concurrent administration of ICB and RT normalizes tumor vasculature, alleviates hypoxia, and increases vessel perfusion to improve immune cell infiltration in solid tumors. Furthermore, we reveal that this TME modulation was linked to stimulation of interferon-γ (IFN-γ) signaling in endothelial cells by activated CD8+ T cell responses, which results in systemic tumor control and establishes long term immunological memory in the neoadjuvant setting. Collectively, these results indicate that immunotherapy sensitizes solid tumors to RT by modulating the tumor microenvironment in an IFN-γ dependent manner, resulting in successful anti-tumor immunity. This research provides a rationale for the concurrent administration of anti PD-1 therapy and radiation therapy to treat radioresistant solid tumors. Citation Format: Annette Wu, Minjeong Kang, Daeyong Lee, Yifan Wang, Kristin M. Huntoon, Betty Y.S. Kim, Wen Jiang. Interferon- γ is required for immunotherapy induced radiosensitivity in solid tumors. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B012.