tbuckley/cabot-search huggingface dataset:
Abstract 1039: Bridging gaps in cancer care: Utilizing large language models for accessible dietary recommendations
Authors: Julia A. Logan, Nicole L. Simone, Sriya Sadhu, Cameo Hazlewood, Sara Burke, Hamidreza Nourzadeh, Yevgeniy Vinogradskiy, Wookjin Choi, Adam P. Dicker, Melissa Denton, Caroline Black, Corey Ciaverelli, Jacqueline Stulb, Amy Leader
Journal: Cancer Research (2025)

Abstract Background: Weight management is directly linked to cancer recurrence and survival; however, oncology nutritional counseling is not typically covered by insurance, creating a disparity among patients without nutritional education and easy food access. Novel ways of imparting personalized nutrition advice are imperative to address this issue. Large language models offer a promising and sustainable path toward dietary advice tailored to individual needs. Objective: This study aimed to assess the capacity of large language models to offer personalized dietary advice to patients with breast cancer. Methods: Thirty-one prompt templates were designed to evaluate the dietary recommendations generated by ChatGPT and Gemini with variations within eight categorical variables, including cancer stage, comorbidity, location, culture, age, dietary guideline, budget, and store. Seven prompts were selected for response from four board-certified dietitians. The responses were then evaluated based on qualitative observations of the large language model-generated grocery lists and meal plans and a quantitative comparison of the calories and macronutrients of large language model- and dietitian-generated meal plans to the Acceptable Macronutrient Distribution Ranges and United States Department of Agriculture daily calorie standards. Results: Large language models generated personalized grocery lists and meal plans, adapting to location, culture, and budget, but not age, disease stage, comorbidities, or dietary guidelines. Gemini provided more comprehensive responses, including visuals and specific prices. While dietitian-generated diets offered more adherent total daily calorie contents to the United States Department of Agriculture’s estimated calorie needs, ChatGPT and Gemini offered more adherent macronutrient ratios to the Acceptable Macronutrient Distribution Range. Conclusions: Large language models can provide personalized dietary advice to cancer patients who may lack access to this care. Recommendations apply to patients with variable food access, socioeconomic means, and cultural preferences and can be a tool to increase health equity. Citation Format: Julia A. Logan, Nicole L. Simone, Sriya Sadhu, Cameo Hazlewood, Sara Burke, Hamidreza Nourzadeh, Yevgeniy Vinogradskiy, Wookjin Choi, Adam P. Dicker, Melissa Denton, Caroline Black, Corey Ciaverelli, Jacqueline Stulb, Amy Leader. Bridging gaps in cancer care: Utilizing large language models for accessible dietary recommendations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1039.
Abstract 96: Elucidating the role of CXCL17/GPR35 axis in breast cancer bone metastasis
Authors: Gunjan Sharma, K. M. Abdullah, Seema Singh, Ajay P. Singh, Jawed A. Siddiqui
Journal: Cancer Research (2025)

Abstract Breast cancer (BC) has a high propensity to metastasize to the bone, but the molecular mechanisms driving bone metastasis (BoM) are not yet fully understood. BC cells establish bidirectional interactions with the bone microenvironment through altered expression of several chemokines and their receptors to facilitate metastasis and niche formation. Various G protein-coupled receptors are involved in oncogenic processes. Recently, it has been reported that G protein-coupled receptor 35 (GPR35), a cognate receptor for CXCL17, plays a significant role in tumor progression, metastasis, and drug resistance; however, its role in the modulation of bone microenvironment has not been elucidated. Here, we analyzed the expression of GPR35 in BC patients using the TCGA database. Furthermore, we also employed immunohistochemistry to examine the expression profile of GPR35 in BC tissue microarray. Our findings revealed high GPR35 expression in BC relative to the normal breast tissue. High GPR35 expression in BC also correlated positively with poor patient outcomes. Moreover, GPR35 expression was elevated in human as well as syngeneic BC bone metastatic cell lines (SCP2, SCP28, and E0771/Bone) compared to their relative parental cell lines (MDA-MB-231 and E0771P), advocating its significant potential in bone metastasis. Since most of the BC bone metastasis is osteolytic (bone destructive) in nature, and osteoblasts (OBs) regulate the osteoclasts (OCs) functions, therefore we examined the effect of conditioned media (CM) from the BC cells treated with either vehicle or rhCXCL17 on OBs and OCs. BC-CM induced bone cell differentiation, which was remarkably significant in OBs and OCs treated with BC-CM of rhCXCL17-treated cells. Together, these findings highlight the critical role of the CXCL17/GPR35 signaling axis in bone microenvironment remodeling supporting BC cell colonization. Citation Format: Gunjan Sharma, K. M. Abdullah, Seema Singh, Ajay P. Singh, Jawed A. Siddiqui. Elucidating the role of CXCL17/GPR35 axis in breast cancer bone metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 96.
Abstract 854: Targeting Irg1 expressed on macrophages in lymph nodes promotes response to mRNA cancer vaccines
Authors: Chao Wan, Wenwen Wei, Xiao Yang, Yeshan Chen, Mengjie Che, You Qin, Qiao Li, Kunyu Yang
Journal: Cancer Research (2025)

Abstract mRNA cancer vaccines show great promise for tumor therapy, but their therapeutic efficacy is limited. Metabolites play critical roles in immunomodulation, however, their role in mRNA cancer vaccines remains unclear. Using metabolome analysis combined with single-cell RNA sequencing, we found that macrophage-derived itaconate increased markedly after ovalbumin-encoding mRNA-lipid nanoparticle (OVA-LNP) injection in activated ipsilateral lymph nodes compared to that in homeostatic contralateral lymph nodes. Depleting the immune-responsive gene 1(Irg1) in macrophages, which encodes the itaconate-production enzyme aconitate decarboxylase (ACOD1), improved the antigen presentation of dendritic cells and the functions of T cells. Knockdown of Irg1 using small interfering RNA (siRNA) combined with OVA mRNA in LNPs enhanced the therapeutic efficacy of mRNA vaccines alone or combined with an anti-programmed cell death-1 antibody. Taken together, our results reveal a link between itaconate and mRNA cancer vaccines, and suggest that targeting Irg1 via siRNA-LNP may be a promising strategy for improving the therapeutic efficacy of mRNA cancer vaccines. Citation Format: Chao Wan, Wenwen Wei, Xiao Yang, Yeshan Chen, Mengjie Che, You Qin, Qiao Li, Kunyu Yang. Targeting Irg1 expressed on macrophages in lymph nodes promotes response to mRNA cancer vaccines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 854.
Abstract 126: Targeting PAR1 in an aggressive blood cancer: A novel strategy to eradicate leukemic stem cells
Authors: Nunki Hassan, Kaitlyn Trajcevski, Jenny Wang
Journal: Cancer Research (2025)

Abstract Acute Myeloid Leukemia (AML) remains a challenging hematologic malignancy with poor prognosis due to the persistence of therapy-resistant leukemic stem cells (LSCs). Current therapeutic strategies often fail to completely eradicate LSCs, leading to relapse. One promising therapeutic target is protease-activated receptor 1 (PAR1), a G-protein-coupled receptor selectively expressed in LSCs. Our research investigates the potential of targeting PAR1 to eliminate LSCs and improve treatment outcomes in AML. High PAR1 expression in a cohort of AML patients had a reduced overall survival (n=163, P&amp;lt;0.001). Lentiviral transduction of PAR1 knockdown and overexpression in mouse LSCs was established. PAR1 and its downstream gene and protein targets were validated utilising RT-qPCR and Western blot, respectively. PAR1 function was assessed with knockdown and PAR1 inhibitor treatment independently, which concurrently reduced colony formation, increased apoptosis, induced cell differentiation, and decreased expression of key self-renewal targets (i.e., ß-catenin and transcriptional factor Tcf7L2) and Gα subunits in LSCs. PAR1 overexpression in pre-LSCs was consistent with knockdown studies, demonstrating significantly increased colony formation and increased expression of key self-renewal genes (i.e. Tcf7l2, Ccnd1). PAR1 inhibitor showcased a dose and time-dependent early and late-stage apoptosis in LSCs, while in parallel reduced self-renewal signature markers and increased pro-apoptotic markers (i.e., cleaved caspase 3, Txnip). Murine models included intravenous transplantation of LSCs and pre-LSCs to evaluate PAR1 function in vivo. Overexpression of PAR1 in pre-LSC accelerated leukemogenesis compared to controls in vivo. Murine models demonstrated a marked reduction in leukemic burden in PAR1 knockdown mice, with prolonged survival compared to controls further enhancing LSC eradication and mitigating relapse in vivo. This innovative study is the first to establish PAR1 as a critical regulator of LSC self-renewal and survival, offering a potential breakthrough in AML therapy. These findings support the clinical development of PAR1 inhibitors as a next-generation treatment in eradicating LSCs, with the potential to overcome current therapeutic limitations and reduce relapse rates in AML patients, ultimately uniting cancer biology and therapeutic innovation. Citation Format: Nunki Hassan, Kaitlyn Trajcevski, Jenny Wang. Targeting PAR1 in an aggressive blood cancer: A novel strategy to eradicate leukemic stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 126.
Abstract 643: Efficacy and safety comparison of CAR-T and blinatumomab immunotherapy as bridge-to-transplant strategy in relapsed/refractory B cell acute lymphoblastic leukemia
Authors: Wenyue Cao, Ningwen Li, Na Wang, Yang Cao
Journal: Cancer Research (2025)

Background: B cell acute lymphoblastic leukemia (B-ALL) remains a therapeutic challenge despite advances. Hematopoietic stem cell transplantation (HSCT) provides a potential cure but is hindered by various limitations. Emerging immunotherapies, including chimeric antigen receptor T cell (CAR-T) therapy and Blinatumomab, have shown potential as bridging strategies to HSCT in relapsed/refractory (R/R) cases. Methods: A retrospective study was conducted at Tongji Hospital from March 2017 to March 2023, involving 36 R/R B-ALL patients who underwent HSCT. Prior to transplantation, 27 patients received CD19/CD22 CAR-T therapy, while 9 received Blinatumomab. Outcomes assessed included the overall survival (OS), progression-free survival (PFS), graft-versus-host disease-free and relapse-free survival (GRFS), and non-relapse mortality (NRM), with comparisons made between treatment groups. Hematopoietic reconstitution and transplant-related complications were also evaluated. Results: The median follow-up time was 28.07 (range: 2.29-92.21) months. The 2-year OS, PFS, GRFS, and NRM of the entire cohort were 76.54%, 54.97%, 40.12%, and 9.93%, respectively. In the CAR-T and the Blinatumomab treatment group before transplantation, the 2-year OS was 73.89% and 88.89% (P=0.862), PFS, was 59.03% and 44.44% (P=0.501), GRFS was 47.86% and 13.89% (P=0.083), and NRM was 8.52% and 11.11% (P=0.713), respectively. Safety profiles were similar with no significant differences observed in hematopoietic reconstitution, infection, the incidence of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD incidence between CAR-T and Blinatumomab groups. Conclusion: CAR-T and Blinatumomab therapies demonstrate comparable safety and efficacy as bridging treatments to HSCT in patients with R/R B-ALL. Further studies are needed to optimize these treatment strategies. Citation Format: Wenyue Cao, Ningwen Li, Na Wang, Yang Cao. Efficacy and safety comparison of CAR-T and blinatumomab immunotherapy as bridge-to-transplant strategy in relapsed/refractory B cell acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 643.
Abstract 956: HB-200: A novel viral vector vaccine platform that can improve immunotherapy treatment in HPV16+ HNSCC
Authors: Sydney Fisher, Matthew Ji, Yuxuan Miao
Journal: Cancer Research (2025)

Abstract Human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OSCC) is the most common head and neck cancer in the United States. While many HPV+ OSCC are curable using current standard treatment, the efficacy of these treatments diminishes when the cancers become metastatic. The viral associated malignancy provides unique opportunities for immunotherapy, however, immune checkpoint inhibitors only induce weak and unsustainable immunity against HPV+ cancer. Thus, there remains a need for new treatment modalities that improve outcomes while also reducing adverse effects. Previously, HB-200, a novel HPV-specific therapeutic vaccine containing two replicating live-attenuated vectors expressing the highly antigenic HPV16 E7E6 protein, has been shown to elicit a more robust anti-tumor immune response alongside chemotherapies compared to standard immunotherapies in clinical trial. However, the underlying mechanisms of why this vaccine can induce stronger immune response than immune checkpoint blockade remains unclear. Here, we utilize mouse models of HPV16 E6/E7+ OSCC to elucidate how HB-200 enhances anti-tumor immunity. To achieve this goal, we first established two complementary HPV16 E6/E7+ oral SCC tumor models: 1) grafting syngeneic MOC2 cells expressing the E6 and E7 oncoproteins of HPV16 on immune-competent C57BL/6 mice; 2) exposing the oral cavity of K14CreER; Rosa26-LSL-E6/E7 mice with 4-NQO to induce spontaneous oral SCCs. With these novel models, mice were then treated with either anti-PD-L1 or HB-200 plus chemotherapy to mimic clinical trials in humans. At 4 weeks post-tumor grafting, we profiled the immune landscape of these tumors by flow cytometry to quantify the frequency of specific CD8 T cell, CD4+ Tfh cell, and B cell populations which we hypothesized to be enriched following HB-200 treatment. This study addresses the central question of how viral immunotherapy can induce stronger immune responses than standard immune checkpoint immunotherapy and better enable T cells to achieve tumor control in HPV-associated cancer, providing an important mechanistic understanding of the HB-200 vaccine platform. Thus, findings from this study give critical insights for optimizing HPV-specific immunotherapy with the exciting potential to translate into novel clinical interventions for HPV+ OSCC patients. Citation Format: Sydney Fisher, Matthew Ji, Yuxuan Miao. HB-200: A novel viral vector vaccine platform that can improve immunotherapy treatment in HPV16+ HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 956.
Abstract 1872: MSH6 modulates PARP inhibitor sensitivity in BRCA-proficient high-grade serous ovarian cancer
Authors: Ou Deng, Thales Nepomuceno, Bin Fang, Eric A. Welsh, Rachael H. Martin, Erin M. George, Alvaro N. Monteiro, Uwe Rix
Journal: Cancer Research (2025)

Abstract Ovarian cancer is the leading cause of gynecologic cancer-related deaths, with high-grade serous ovarian cancer (HGSOC) being the most common subtype. While BRCA1/2 deficiencies are established biomarkers to predict PARP inhibitor (PARPi) sensitivity, some HGSOC patients with BRCA-proficient tumors also respond to PARPi therapy. However, the mechanisms driving PARPi sensitivity in BRCA-proficient HGSOC remain poorly understood. We hypothesized that PARP1 protein complex composition and PARylation-mediated signaling regulate PARPi sensitivity or resistance in BRCA-proficient HGSOC. Through viability screening of BRCA-proficient ovarian cancer cell lines treated with PARPis we identified three sensitive and three resistant lines. Chemical proteomics with rucaparib showed enrichment of PARP1, PARP2, and associated binding proteins, with notably higher MSH6 levels in sensitive cell lines compared to resistant ones. Co-immunoprecipitation further revealed differences in PARP1-MSH6-PARP2 complex compositions between sensitive and resistant cells lines. Genetic knockout or knockdown of MSH6 via CRISPR and siRNA, respectively, conferred resistance to rucaparib, with a more pronounced effect in sensitive cells. To investigate downstream signaling, we performed ADP-ribosylation proteomics using clickable NAD+ analogs, uncovering distinct PARylation profiles between sensitive and resistant lines. CHAF1A, a known MSH6 binder and PARP1 substrate, was identified in PARPi-sensitive cells. More importantly, MSH6 knockdown elevated CHAF1A levels, while rucaparib treatment reduced CHAF1A expression, particularly in sensitive cells. These findings suggest that CHAF1A upregulation through MSH6 inhibition may rescue PARPi-induced cell death. This study integrates chemical proteomics and ADP-ribosylation analysis to delineate the interplay between PARP1 complex composition and signaling dynamics in PARPi response. Our findings highlight MSH6 and CHAF1A as critical modulators of PARPi sensitivity, providing new insights into resistance mechanisms and identifying potential biomarkers to improve PARPi efficacy in BRCA-proficient HGSOC. Citation Format: Ou Deng, Thales Nepomuceno, Bin Fang, Eric A. Welsh, Rachael H. Martin, Erin M. George, Alvaro N. Monteiro, Uwe Rix. MSH6 modulates PARP inhibitor sensitivity in BRCA-proficient high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1872.
Abstract 19: ACTL6A promotes the progression of prostate cancer by modulating GLI1 expression in the Hedgehog signaling pathway
Authors: Li-Hsin Cheng, Kelvin K. Tsai
Journal: Cancer Research (2025)

Abstract The disruption of tissue organization is a major contributing factor to the malignant transformation of glandular epithelium, including prostate glands. Three-dimensional organotypic cultures have facilitated the discovery of molecular mechanisms underlying malignant progression. Using a robotic-assisted MicroWestern Array-based proteomics screening, we identified that the protein abundance level of the chromatin remodeling factor ACTL6A is upregulated in disorganized prostate epithelial organoids. We showed that ACTL6A critically regulates prostate glandular morphogenesis as its overexpression led to glrandular transformation. Consistent with this finding, ACTL6A expression is higher in human prostate cancer compared to normal prostate tissue and is associated with poor clinical prognosis. At the functional level, tthe knockdown of ACTL6A expression in PCa cells attenuated stemness and tumorigenesis in vitro and PCa progression in an orthotopic mouse tumor model. Intriguingly, screening of development-associated signaling pathways identified the Hedgehog (Hh) pathway, whose activity and the target genes were reduced by the loss of ACTL6A expression in PCa cells. Further mechanistic and molecular studies revealed that ACTL6A regulates the protein abundance level of GLI1, the key transcriptional factor in Hh-pathway, PCa cells by disabling its ubiquitin-dependent proteosomal degradation. Our study thus illuminated a novel oncogenic mechanism mediated by the ACTL6A-GLI1-Hh signaling axis in PCa, which may have diagnostic and therapeutic implications. Citation Format: Li-Hsin Cheng, Kelvin K. Tsai. ACTL6A promotes the progression of prostate cancer by modulating GLI1 expression in the Hedgehog signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 19.
Abstract 1033: Racial and ethnic disparities in human papillomavirus vaccination among US-born and foreign-born adults aged 18 to 26 years in the United States
Authors: Itunu Sokale, Jane Montealegre, Ann Amuta-Jimenez, Abiodun Oluyomi, Aaron Thrift
Journal: Cancer Research (2025)

Abstract Background: Human papillomavirus (HPV) is linked to multiple cancers that can be prevented through vaccination. Despite the availability of safe and effective vaccines for HPV, vaccination rates in the US remain suboptimal. While the optimal age for vaccination is in childhood and adolescence, Vaccination recommendations include adults through age 26 who missed being vaccinated as children and adolescents. There are limited data about disparities among adults eligible for catch-up HPV vaccination. We conducted a comprehensive examination of HPV vaccination among US young adults disaggregating the group by race/ethnicity and nativity status to identify subgroups that may require additional interventions. Methods: We analyzed 2019 and 2022 data of individuals aged 18-26 years from the National Health Interview Survey. Unadjusted and adjusted generalized linear models using Poisson regression with log link were used to examine the associations between receipt of at least 1 dose of HPV vaccine and race/ethnicity and nativity (i.e., US- versus foreign-born). Results: The overall receipt of at least 1 dose of HPV vaccine was 47.5%. The vaccination rate among US-born was 49.7% versus 31.9% among foreign-born individuals, with an adjusted prevalence ratio (APR) of 0.72; (95% CI, 0.62-0.82). Females had a higher vaccination rate (57%) than males (37.8%), Foreign-born black individuals (APR 0.31; 95% CI, 0.13-0.70) were less likely to be vaccinated against HPV than foreign-born white individuals, while US-born Asians (APR), 1.27; 95% CI, 1.09-1.48) had a higher prevalence of the vaccination than the US-born White group. Foreign-born Asian (APR 0.60; 95% CI, 0.46-0.77), Black (APR 0.27; 95% CI, 0.12-0.61), and Hispanic (APR 0.76; 95% CI, 0.60-0.97) populations were less likely to be vaccinated against HPV than their respective US-born counterparts. Conclusions: There are profound HPV vaccination inequalities among US young adults, with particularly low vaccine coverage among racially and ethnically minoritized immigrant populations. Impact: The study findings could be integrated into designing effective targeted catch-up HPV vaccination interventions with race/ethnicity- and nativity-specific considerations to reduce HPV vaccination disparities. Citation Format: Itunu Sokale, Jane Montealegre, Ann Amuta-Jimenez, Abiodun Oluyomi, Aaron Thrift. Racial and ethnic disparities in human papillomavirus vaccination among US-born and foreign-born adults aged 18 to 26 years in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1033.