tbuckley/cabot-search huggingface dataset:
Abstract 5944: Trend and treatment pattern of vulvar cancer in a single academic hospital in South Africa
Authors: Adekunle Emmanuel Sajo, Edwin Mnisi, Cathy Visser, Sheynaz Bassa, Greta Dreyer
Journal: Cancer Research (2025)

Abstract The incidence of vulvar cancer is increasing among younger women mainly to the coinfection of HIV and HPV infections which drive majority of cases in sub-Saharan Africa. We aimed to describe the trend and treatment patterns of vulvar cancer at the Steve Biko Academic Hospital, South Africa. This was a retrospective cross-sectional study between 1st January 2012 and 31st December 2022. Data were extracted from the participants’ medical records on the demographics, medical history, histologic characteristic and treatment. We analyzed 317 vulvar cancer cases. The mean age was 45±12 yrs. Of the patients, 40% were younger than 40yrs. More than 77% (248) were living with HIV (WLHIV) with a mean CD4 count of 481.8 cell/µL. Of the WLHIV, 82% were virally suppressed. 64% of cases presented in advanced stage (stages III &amp; IV). During the study period, the average age decreased from 56yrs to 40yrs in a linear fashion, p 0.012 while the number of cases rose exponentially. There was a steady decline of cervical cancer cases during the study period in contrast to the rising vulvar cancer. When the study period was halved, the mean age was significantly lower in the later half, 46yys vs 44yrs, p 0.001. Among the cases, the proportion of women with HIV increased steadily from 20% in 2012 to highest proportion of 98% in 2021, p 0.001. 70% of those who had surgery (152) had radical vulvectomy with nodal dissection. Of the total who had radiotherapy (114), only 47% had curative radiotherapy. The mean radiotherapy (RT)completion time was 48 days. 16% (51) of the total patient did not receive any treatment due to ill-health or failure to present for RT. Table 1tbl1 shows the comparison of our study with a previous study from the institution (Mnisi et al 2019). Vulvar cancer has transitioned to be a disease of the young. HIV is a major risk factor for vulvar cancer in our environment. Adequate surveillance of the genital area and screening of at risk group might help to stem the tide. Comparison with previous study from the University of Pretoria Mnisi et al 2019 Current study Study period 2001-2013 2012-2022 Institution Data from 2 hospitals single institutional data Average age 43yrs 45yrs Proportion of HIV 43.7% 78% Disease stage 35.9% were advanced 64% were advanced Proportion of HIV positive below 40yrs 29.6% 98% Tumour size &amp;gt;4cm 88.8% 78% Positive nodes 36.7% 35.8% Total number of cases 134 317 Treatment 40% had surgery 48% had surgery Citation Format: Adekunle Emmanuel Sajo, Edwin Mnisi, Cathy Visser, Sheynaz Bassa, Greta Dreyer. Trend and treatment pattern of vulvar cancer in a single academic hospital in South Africa [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 5944.
Abstract 5981: Over 200! The largest BaF3-EGFR engineering cell lines collection, a useful platform for novel drug discovery
Authors: Yao Tang, Guoqian Wang, Tingduo Lv, Jingxiao Xu, Yao Peng, Jinying Ning, Feng Hao
Journal: Cancer Research (2025)

Abstract The epidermal growth factor receptor (EGFR) is a cell-surface receptor tyrosine kinase that belongs to the ERBB family, which includes HER1 (EGFR), HER2, HER3, and HER4. Each of these receptors has three key layers: an input layer, a signal-processing core, and an output layer. EGFR is activated primarily through ligand binding, with ligands such as EGF, TGF-alpha, HB-EGF, AR, EPR, BTC, and epigen. However, mutations or overexpression of EGFR can lead to ligand-independent activation. Once activated, EGFR triggers various downstream signaling pathways, such as PI3K-AKT, JAK-STAT, RAS-MEK/ERK, and PLC-gamma-PKC, which enhance cell proliferation, survival, and resistance to cell death.The overexpression or increased activity of EGFR is linked to several cancers, including non-small cell lung cancer (NSCLC), colon cancer, head and neck cancer (HNC), pancreatic cancer, breast cancer, and brain cancer. Recognizing EGFR as a driver gene has accelerated the development of targeted anticancer therapies, such as monoclonal anti-EGFR antibodies (cetuximab, panitumumab) and small molecule receptor tyrosine kinase inhibitors (TKIs). The first generation of EGFR TKIs, like gefitinib and erlotinib, specifically target mutations such as L858R and exon 19 deletions. To address resistance to these early inhibitors, second-generation EGFR TKIs (afatinib, dacomitinib) were developed. The EGFR T790M mutation is a major mechanism of resistance to both first and second-generation TKIs. Osimertinib, a third-generation TKI, was approved for use in EGFR-mutated NSCLC following the failure of first- and second-generation TKIs, although the EGFR C797S mutation limits its effectiveness. Fourth-generation EGFR TKIs, including BLU-945 and BBT-176, are under clinical evaluation but are not yet approved.We have created more than 200 Ba/F3-EGFR engineered cell lines, making this the largest in vitro and in vivo platform for drug discovery with the widest range of mutant cells. These cell lines include almost all clinically significant EGFR mutations, such as common mutations like L858R and exon 19 deletions, as well as rare mutations like L861Q, S768I, and combinations of mutations like L858R/T790M, Del19/T790M, and triple mutations. These Ba/F3-EGFR engineered cell lines are valuable tools for developing and assessing next-generation EGFR inhibitors and for studying newly acquired resistance mutations in EGFR. Citation Format: Yao Tang, Guoqian Wang, Tingduo Lv, Jingxiao Xu, Yao Peng, Jinying Ning, Feng Hao. Over 200! The largest BaF3-EGFR engineering cell lines collection, a useful platform for novel drug discovery [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 5981.
Abstract 3658: LINE1 ORF1P is a druggable target for early onset colorectal cancer and cancer prevention
Authors: Dan Zhao, Yifei Wang, Praveen Neeli, Yong Li
Journal: Cancer Research (2025)

Colorectal cancer is the second most common cause of cancer deaths in the United States. In recent years, there has been a surprising increase in early-onset colorectal cancer, making it the leading cause of cancer-related death in young men under 50 years old. With aging as the primary risk factor for human cancers, we argue that anti-aging agents are a viable option for cancer prevention. One common scientific approach in anti-aging is partial cell reprogramming using Yamanaka factors. However, there is concern that activation of stem cell-specific transcription factors may promote tumor formation. Transposable element LINE1 ORF1p expression has been reported to be elevated in both aging and cancer across multiple species and cancer types, making it a promising target to address both aging and cancer simultaneously. Interestingly, we discovered that LINE-1 expression is higher in the serum of early-onset colorectal cancer patients and hypothesize that ORF1p activation accelerates aging and promotes cancer progression. Using artificial intelligence-based small molecule drug screenings from 10 million compounds, we identified two LINE1 ORF1p targeting drugs, B7 and C1, that significantly kill cancer cells but not normal cells in vitro. A surface plasmon resonance (SPR) assay confirmed high binding affinity of B7 and C1 to the ORF1p protein. Consistently, B7 and C1 inhibited retrotransposition using a LINE1-specific retrotransposition reporter assay. When we transplanted ORF1p high-expressing human cancer cells into NSG mice, treatment with B7 or C1 significantly inhibited tumor growth by 57% (C1) and 75% (B7) and improved survival of tumor-bearing mice compared to vehicle control. Additionally, we designed an antibiotic-free nanoplasmid DNA vaccine targeting ORF1p. We confirmed its high expression level in vitro and then performed electroporation of the DNA vaccine using Ichor's TriGrid™ intramuscular electroporation technology. In a prophylactic model, we vaccinated the mice three times before inoculating them with syngeneic mouse colon tumor cells. The vaccination significantly delayed tumor onset and inhibited tumor growth by more than 50%. In conclusion, our data suggest ORF1p as a druggable target and a promising DNA vaccine target for both cancer prevention and treatment in human early-onset colorectal cancer. Citation Format: Dan Zhao, Yifei Wang, Praveen Neeli, Yong Li. LINE1 ORF1P is a druggable target for early onset colorectal cancer and cancer prevention [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 3658.
Abstract 5917: A novel ROR1 antibody with high specificity and sensitivity for predictive biomarker detection in various tumor types
Authors: Xin Zhang, Qianqian Lian, Qian Qian, Dan Lu, Yanling Liu, Ying Tong, Qingyang Gu
Journal: Cancer Research (2025)

Abstract ROR1, a receptor tyrosine kinase-like orphan receptor, is a key mediator of non-canonical Wnt signaling and plays a critical role in cancer progression. ROR1 is selectively and highly expressed in various solid tumors and hematological malignancies while absent in normal adult tissues, making it a promising target for cancer therapy. Despite this potential, the lack of effective tools has hindered sensitive detection of ROR1 in patient tumor samples by IHC. To address this, we have developed a recombinant rabbit monoclonal antibody in-house, demonstrating superior sensitivity and specificity across multiple methodologies compared to existing antibodies. Additionally, we have established standardized interpretation criteria and performed an extensive epidemiological survey across ROR1-associated cancer types, reporting the following detection rates: 45% in pancreatic cancer (n=40), 39% in ovarian cancer (n=150), 48% in lung adenocarcinoma (n=140), 15% in endometrial cancer (n=97), 18% in triple-negative breast cancer (n=110), 23% in mesothelioma (n=47), and 10% in esophageal squamous carcinoma (n=70). These results validate this antibody as a reliable tool for clinical biomarker detection, potentially advancing ROR1-targeted cancer treatment. Citation Format: Xin Zhang, Qianqian Lian, Qian Qian, Dan Lu, Yanling Liu, Ying Tong, Qingyang Gu. A novel ROR1 antibody with high specificity and sensitivity for predictive biomarker detection in various tumor types [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 5917.
Abstract 2267: Mapping genetic risk for Barrett's esophagus and esophageal adenocarcinoma to key tissues and transcriptional regulators
Authors: Elnaz Naderi, Xu Zhang, Kathryn Graz, Carlos Maj, Johannes Schumacher, Li Yan, Matthew F. Buas
Journal: Cancer Research (2025)

Abstract Background: Esophageal adenocarcinoma (EAC), the most common subtype of esophageal cancer in Western countries, typically arises from Barrett’s esophagus (BE), a pre-neoplastic condition marked by replacement of the normal esophageal epithelium with intestinal metaplasia. Genome-wide association studies (GWAS) have revealed a substantial heritable component of BE/EAC susceptibility, but mechanistic understanding remains limited. Identifying tissues, cell types, and transcriptional regulators mediating genetic risk is essential for elucidating etiologic pathways and defining novel molecular targets for translation. Methods: We employed a permutation-based approach to evaluate the enrichment of BE/EAC-associated variants in open chromatin regions (OCRs) across &amp;gt;50 diverse tissues and cell types. For a subset of implicated tissues, we further assessed enrichment in the binding regions of multiple transcription factors (TFs) using ChIP-seq profiles, with complementary analyses based on DNAse-I footprinting data and motif scanning. Multiple testing correction was implemented using the false discovery rate (FDR&amp;lt;0.05). Results: BE/EAC variants were significantly enriched in OCRs of gastrointestinal tissues, particularly fetal stomach (OR = 1.6, P = 6e-04) and fetal large intestine (OR = 1.5, P = 1.5e-03). Enrichments were also observed in muscle (OR = 1.5, P = 9e-04) and fibroblast (OR = 1.4, P = 8.8e-03) cells, suggesting a broader multi-lineage regulatory landscape. Key TFs implicated in subsequent testing included GATA6 (OR = 3.0, P &amp;lt;1e-04) and GATA4 (OR = 2.2, P = 2e-04) in GI tissues; EZH2 in muscle cells (OR = 5.7, P = 2e-04); and EZH2 (OR = 3.5, P &amp;lt;1e-04) and AR (OR = 1.4, P = 1.2e-03) in fibroblast cells. Conclusions: This study indicates that BE/EAC risk variants act through regulatory elements across diverse tissues, with prominent roles suggested in gastrointestinal, muscle, and stromal cells. The significant enrichment signals for transcription factors such as GATA6, GATA4, and EZH2 underscore their regulatory importance in GI-tract development and BE/EAC pathogenesis. These insights enhance our understanding of the cellular/molecular origins and genetic underpinnings of BE/EAC, providing a promising foundation for experimental and translational studies targeting specific transcriptional regulatory networks. Citation Format: Elnaz Naderi, Xu Zhang, Kathryn Graz, Carlos Maj, Johannes Schumacher, Li Yan, Matthew F. Buas. Mapping genetic risk for Barrett's esophagus and esophageal adenocarcinoma to key tissues and transcriptional regulators [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 2267.
Abstract 5942: Association of microsatellite instability status with pathologic complete response and tumor downstaging in locally advanced rectal cancer
Authors: Mohyeddine El Sayed, Sassine Youssef, Raymond Dubois
Journal: Cancer Research (2025)

Abstract Background: Two primary genomic instability pathways contribute to rectal carcinogenesis: microsatellite instability (MSI) and chromosomal instability, known as microsatellite stable (MSS). MSI rectal cancers generally have a better prognosis—attributed to enhanced immunogenicity, distinct molecular pathways, and reduced metastatic potential. This study assesses the impact of MSI status on pathologic complete response (pCR) and tumor downstaging after neoadjuvant treatment. We hypothesized that MSI rectal cancers are associated with higher odds of achieving pCR and tumor downstaging. Methods: A retrospective analysis was performed using the National Cancer Database, including patients aged ≥20 years diagnosed with stage II-III rectal cancer between 2004 and 2020 with documented MSI status. All patients underwent surgical resection, chemotherapy, and radiotherapy. Collected data encompassed demographics, tumor size and grade, TN stage, lymphovascular invasion, perineural invasion, and immunotherapy. MSI status was categorized as MSS, MSI-low (MSI-L), and MSI-high (MSI-H). The primary outcome is pCR, defined as the absence of tumor in the pathological specimen (T0/x, N0/x). Tumor downstaging was assessed by comparing pathological T or N stage with clinical staging. Multivariable binary logistic regression analyzed the impact of MSI status on pCR and tumor downstaging, adjusting for significant covariates. Results: Of the 5, 124 patients included, 93.5% were MSS, 3.1% MSI-L, and 3.4% MSI-H. Immunotherapy was administered to 1.1% of MSS, 1.9% of MSI-L, and 3.5% of MSI-H patients. MSI tumors were less likely to achieve pCR compared to MSS tumors (OR = 0.62; P = 0.023). Specifically, MSI-L tumors had significantly lower odds of pCR (OR = 0.40; P = 0.011), whereas MSI-H tumors did not differ significantly from MSS tumors. For T downstaging, MSI tumors were less likely to have a reduced pathological T stage (OR = 0.72; P = 0.009). MSI-H tumors were associated with lower odds of T downstaging (OR = 0.69; P = 0.027), while MSI-L tumors showed no significant impact. Neither MSI-L nor MSI-H status significantly affected N downstaging. Conclusion: Despite a better overall prognosis of MSI tumors, they are less likely to achieve pathologic complete response and T downstaging following neoadjuvant treatment. Additionally, MSI-L and MSI-H tumors exhibit distinct clinical outcomes in rectal cancer, indicating they should be considered separate entities in clinical management. Citation Format: Mohyeddine El Sayed, Sassine Youssef, Raymond Dubois. Association of microsatellite instability status with pathologic complete response and tumor downstaging in locally advanced rectal 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 5942.
Abstract 5943: The impact of radiotherapy on prognosis in microsatellite stable rectal cancer: A national analysis
Authors: Mohyeddine El Sayed, Sassine Youssef, Raymond N. DuBois
Journal: Cancer Research (2025)

Background: Approximately 80-85% of rectal cancer cases are microsatellite stable (MSS), indicating a functional mismatch repair (MMR) system. Rectal cancer patients with microsatellite instability (MSI) exhibit better survival rates, mainly due to enhanced treatment responses linked to high tumor mutational burden (TMB). Radiotherapy (RT) induces DNA damage, increasing TMB and immune recognition. We hypothesize that RT improves prognosis in MSS rectal cancer patients. Methods: A retrospective study was conducted using the National Cancer Database (NCDB), including patients aged ≥20 years diagnosed with MSS rectal cancer between 2004 and 2020 with documented tumor stages. All patients underwent surgical resection, chemotherapy, and immunotherapy. Collected data encompassed demographics, tumor grade, TNM stage, KRAS mutation status, lymphovascular invasion, and perineural invasion. RT was categorized into short-course RT (SC-RT; 25 Gy) and long-course RT (LC-RT; 45-54 Gy). The impact of RT on overall survival was assessed using multivariable Cox proportional hazards regression, adjusting for variables significant in univariate analysis. Results: Of the 460 patients included, 70.9% received RT, while 29.1% did not. RT recipients demonstrated a 40% reduction in mortality risk compared to non-recipients (P = 0.001). Specifically, SC-RT and LC-RT were associated with 39% (P = 0.042) and 40% (P = 0.002) lower mortality risks, respectively. In stage II-III patients, LC-RT significantly reduced mortality risk (HR: 0.26, P &amp;lt; 0.001), whereas SC-RT showed no significant impact. In stage IV patients, neither SC-RT nor LC-RT significantly affected prognosis. Conclusion: Radiotherapy is associated with improved prognosis in MSS rectal cancer patients, particularly with long-course RT in stages II-III. These findings advocate for clinical trials to further evaluate the role of RT in MSS rectal cancers. Citation Format: Mohyeddine El Sayed, Sassine Youssef, Raymond N. DuBois. The impact of radiotherapy on prognosis in microsatellite stable rectal cancer: A national analysis [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 5943.
Abstract 1511: Cancer adaptation to acidic tumor microenvironment
Authors: Manami Hasegawa, Keisuke Maede, Miyuki Nishida, Xu Bo, Sho Aki, Rika Tsuchida, Tsuyoshi Osawa
Journal: Cancer Research (2025)

Cancer cells exhibit a characteristic metabolic pattern known as the Warburg effect, which upregulates glycolysis even in aerobic environments. As a result, cancer cells are exposed to an acidic environment due to enhanced excretion of proton and lactate. We have previously reported that this acidic tumor microenvironment induces the activation of the cholesterol biosynthesis pathway and the accumulation of N1-acetylspermidine. Although the acidic tumor microenvironment is known to suppress cancer cell proliferation, the survival strategies employed by cancer cells under such harsh conditions remain unclear. This study aims to elucidate the cell death pathways triggered by acidic pH using an environment even more acidic than physiological conditions and to reveal how cancer cells evade such cell death under physiological conditions. Live imaging was performed by exposing the cervical cancer cell line HeLa to an acidic environment (pH 5.6), which confirmed that cell death with membrane rapture was induced. Furthermore, in the pancreatic cancer cell line PANC1, phosphorylation of RIP1 and MLKL was observed, and cell death was suppressed by treatment with Nec-1, an inhibitor of RIP1. These findings identified Necroptosis induced under pH5.6.In addition, PANC1 cells that transitioned to a floating state under acidic conditions (pH 5.6-6.8) regained their adhesion and proliferation abilities when cultured under normal tissue pH conditions (pH 7.4). These findings indicate that some of the floating cells under acidic conditions avoid cell death and adopt certain survival strategies. Then, RNA-seq was performed on cells fractionated into those in suspension and those remaining adherent under pH6.8. Pathways related to the acquisition of stemness such as HDACs deacetylation pathway and PRC2 methylation pathway were observed to be active in the floating cells. Furthermore, the upregulation of EMT transcription factors was also confirmed. Furthermore, we cultured PANC1 cells under pH6.8, using a genome-wide CRISPR-Cas9 knockout screening system over a 30-day time course and identified key genes essential for the acquisition of tolerance to acidic tumor microenvironment. We elucidated a mechanism in pancreatic cancer cells whereby Necroptosis is avoided in physiologically acidic environments. This cell death-avoidance pathways under acidic conditions could potentially be applied to the development of novel therapeutic strategies that induce cell death in pancreatic cancer cells, which are highly influenced by the tumor microenvironment, particularly in acidic conditions. Citation Format: Manami Hasegawa, Keisuke Maede, Miyuki Nishida, Xu Bo, Sho Aki, Rika Tsuchida, Tsuyoshi Osawa. Cancer adaptation to acidic tumor microenvironment [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 1511.