tbuckley/cabot-search huggingface dataset:
Abstract 4234: Synergistic anti-proliferative effects of JIN-001, a novel HSP90 selective inhibitor, in combination with platinum-based drugs in ovarian cancer cell lines
Authors: Jue Young Kim, Ha-Yeon Shin, Anna Jo, Ethan Seah, Choonok Kim, Jae-Hoon Kim
Journal: Cancer Research (2025)

Abstract Introduction: Heat shock proteins (HSPs) have been considered as a promising therapeutic target for ovarian cancer (OC), the most lethal gynecologic malignancy. HSPs facilitate tumor cell adaptation to short-term stress, promoting the development of more malignant phenotypes and the acquisition of resistance to therapeutic treatments over time. To date, Clinical trials of HSP90 inhibitors have shown modest benefits in advanced cancer patients, with no sufficient efficacy as monotherapy. Here, We investigated the anti-proliferative effects of JIN-001, a selective HSP90i, combined with platinum-based drugs in OC cell lines. Material and methods: We examined the co-treatment effects of JIN-001 and paclitaxel (PTX) or cisplatin (Cis, platinum-based) on viability in OC cell lines (OV90, TOV21G, and OVCAR3) and drug-resistance sublines (OV90/PTX200, TOV21G/PTX100, and OVCAR3-CisR). Drug-resistant OC sublines were generated by gradually exposing OC cells to increasing concentrations of PTX or Cis. Each drug was tested either for monotherapy or in 1:1 ratio combination. Also, we assessed the synergistic anti-proliferative effects of JIN-001 (0.1 or 0.05 μM) with Cis on OVCAR3 and OVCAR3-CisR. Results: Co-treatment of JIN-001 with PTX or Cis reduced IC50 in drug-resistant OC sublines compared to PTX or Cis alone. The IC50 of JIN-001 at a fixed dose in combination with Cis were lower in the OVACAR3 and OVCAR-CisR, compared to the single treatment. IC50 (μM) are shown below. Conclusion: The combination of JIN-001 with PTX or Cis enhanced anti-proliferative effects and reduced IC50 in OC cell lines and drug-resistant sublines compared to monotherapy. This suggests JIN-001’s potential as a combination therapy with platinum-based drugs in OC patients. Further studies are needed to examine whether the combination therapy of JIN-001 and the conventional drugs decelerates the tumor’s ability to adapt and develop drug resistance. Citation Format: Jue Young Kim, Ha-Yeon Shin, Anna Jo, Ethan Seah, Choonok Kim, Jae-Hoon Kim. Synergistic anti-proliferative effects of JIN-001, a novel HSP90 selective inhibitor, in combination with platinum-based drugs in ovarian cancer cell lines [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 4234.
Abstract 4191: Combining artificial intelligence and human expertise in pursuit of novel PolQ inhibitors
Authors: Allan M. Jordan, Ageo Miccoli, Annabelle Charnock, Alexis Denis, Euan Fordyce, Cameron Franklin, Ennys Gheyouche, Ian Henderson, Christopher Housseman, Maxime Laugeois, Jean-Christophe Meillon, Stuart Onions, Quentin Perron, Clementine Pescheteau, Emilie Pihan, Mark Reeves, Kirsty Rooney, Hannah Rowlands, Kamaldeep Sumal, Franck Le Vaillant, Graeme Walker
Journal: Cancer Research (2025)

Abstract DNA polymerase theta (POLθ or POLQ) recently emerged as a new promising drug target for the treatment of homologous recombination (HR) deficient tumours. This unique fusion protein comprises both DNA polymerase (Pol) and DNA helicase domains that function together to facilitate multiple DNA repair mechanisms. Small molecule approaches to target both domains have been described throughout the last decade and have shown potent and selective HR-deficient tumor cell death in vitro and in vivo. Despite the growing number of advanced PolQ polymerase inhibitors reported in the literature, significant ADME liabilities remain associated with the current reported scaffolds. To address this issue, machine-based learning methodologies were envisioned to act as a potential aid for medicinal chemistry efforts and help drive identification of chemical matter that might reside outside of the typical toolbox of small molecule design ideas. Using the Makya generative AI platform, synergistically with traditional knowledge-based approaches, we have identified novel small molecule PolQ polymerase domain inhibitors. One chemotype, with an embedded oxime motif, has demonstrated potent biochemical activity and comparable cell activity to known tool compounds. A follow-up library of functionalised oxime derivatives, with varying compositions of donor and acceptor motifs, was synthesized to probe the chemical space further which demonstrated improved biochemical potency on the original hit matter. Initial ADME profiling suggests that these ligands possess properties that represent a good starting point for a lead optimisation campaign. Herein, we report key findings from the initial phase of development of our small molecule PolQ inhibitors. Citation Format: Allan M. Jordan, Ageo Miccoli, Annabelle Charnock, Alexis Denis, Euan Fordyce, Cameron Franklin, Ennys Gheyouche, Ian Henderson, Christopher Housseman, Maxime Laugeois, Jean-Christophe Meillon, Stuart Onions, Quentin Perron, Clementine Pescheteau, Emilie Pihan, Mark Reeves, Kirsty Rooney, Hannah Rowlands, Kamaldeep Sumal, Franck Le Vaillant, Graeme Walker. Combining artificial intelligence and human expertise in pursuit of novel PolQ inhibitors [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 4191.
Abstract 5560: Exploring the role of Wnt, NFκb, and PI3 kinase pathways in oxaliplatin-resistant triple-negative breast carcinoma cell line
Authors: Asif Ahmad, Sheerien Rajput, Areeb Ahmed, Kulsoom Ghias, Azhar Hussain Rajabali
Journal: Cancer Research (2025)

Breast cancer (BCa) is one of the major causes of mortality and morbidity in women globally. Triple negative breast cancer (TNBC) is known for its aggressive nature and is associated with high recurrence and metastasis with poor overall survival; 50% of the patients relapse in the first three years. Development of metastasis and drug resistance impacts survival in TNBC patients. The reasons for drug resistance and metastasis are complex and involve dysregulation of different cell signaling pathways, such as Wnt/β-catenin, NFκB and PI3K/AKT. Clinical studies have shown a favorable response to combination therapy using oxaliplatin in the treatment of metastatic breast cancer. This study explored the role of Wnt/β-catenin, NFκB and PI3K/AKT survival pathways in oxaliplatin-resistant TNBC cell line in vitro. Oxaliplatin-resistant clones were developed in the TNBC cell line MDA-MB-231 through sequential treatment with increasing doses of oxaliplatin. Differential gene expressions between chemoresistant clones and parental cells revealed the dysregulation of resistance-related genes, such as at 4µM treatment CD44 (p&amp;lt; 0.001), COX-2 (p &amp;lt; 0.001), ABCG2, BCL-2 (p &amp;lt; 0.05) and BAX (p &amp;lt; 0.01), alongside a shift towards a mesenchymal phenotype in resistant clones. Signaling pathways were altered, such as the upregulation of β-catenin in the Wnt/β-catenin pathway, Rel-A and NFκB1 in the NFκB pathway, and differential expression of AKT1, PIK3CA and mTOR1 in the PI3K/Akt pathway. Additionally, resistant clones displayed G2/M cell cycle arrest. The findings of the study enhance the understanding of drug resistance mechanisms in triple-negative breast cancer (TNBC) and identify possible targets for therapy. Citation Format: Asif Ahmad, Sheerien Rajput, Areeb Ahmed, Kulsoom Ghias, Azhar Hussain Rajabali. Exploring the role of Wnt, NFκb, and PI3 kinase pathways in oxaliplatin-resistant triple-negative breast carcinoma cell line [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 5560.
Abstract 2133: KA-2887-LD38: a novel bispecific antibody-drug conjugate (ADC) targeting both EGFR and PD-L1
Authors: Guojin Wu, Chuanying Xu, Weihong Nian, Zhengcheng Guo, Jiabei Liang, Feng He, Qing Zhou, Jinying Ning
Journal: Cancer Research (2025)

Abstract PD-L1 is widely expressed across various cancer types and suppresses immune responses against tumor cells. EGFR is also highly expressed in many solid tumors and plays a key role in driving tumor growth. Targeting the PD-1/PD-L1 signaling pathway and the EGF/EGFR signaling pathway using antagonistic antibodies or ADCs has shown promising results in cancer therapy. However, both approaches can lead to undesirable "on-target/off-tumor" effects. Co-expression of PD-L1 and EGFR is rare in normal tissues but is commonly observed in most PD-L1-expressing tumor cells. In this study, we developed a bispecific antibody, KA-2887, using our common light chain antibody discovery platform to target both EGFR and PD-L1. This bispecific antibody was then used to construct the ADC KA-2887-LD38. KA-2887-LD38 has a conventional IgG1 structure, conjugated with LD-38, an Escugen proprietary ADC platform composed of TopIi payload and highly hydrophilic stable cleavable linker. It binds to EGFR with an affinity of 3.7 nM and to PD-L1 with an affinity of 0.6 nM. KA-2887-LD38 effectively blocks both the interaction between EGF and EGFR, and the interaction between PD-1 and PD-L1.The expression of EGFR on tumor cells enhances the inhibitory effect of KA-2887-LD38 on the PD-1/PD-L1 interaction, and vice versa. Compared to monoclonal antibodies targeting PD-L1, KA-2887-LD38 shows a much faster internalization rate when binding to tumor cells co-expressing EGFR and PD-L1. In vitro, KA-2887-LD38 demonstrates cytotoxicity against tumor cells expressing either EGFR and PD-L1 together or EGFR alone, but has a weaker effect on tumor cells expressing only PD-L1. Tumor cells co-expressing EGFR and PD-L1 are more sensitive to KA-2887-LD38. Additionally, KA-2887-LD38 exhibits strong bystander killing activity. Xenograft mouse tumor models show that KA-2887-LD38 strongly inhibits the growth of various tumor types, including NSCLC, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma. Toxicity studies on KA-2887-LD38 are ongoing. The results suggest that KA-2887-LD38 holds significant potential for the treatment of a variety of solid tumors. Citation Format: Guojin Wu, Chuanying Xu, Weihong Nian, Zhengcheng Guo, Jiabei Liang, Feng He, Qing Zhou, Jinying Ning. KA-2887-LD38: a novel bispecific antibody-drug conjugate (ADC) targeting both EGFR and PD-L1 [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 2133.
Abstract 4521: Quilting of flaps reduces drain effluent without significantly increasing duration of surgery in mastectomy a low resource setting
Authors: AbdulRazzaq O. Lawal, Jimoh O. Hassan, Adewumi Alabi, Oluwole A. Atoyebi
Journal: Cancer Research (2025)

Abstract Introduction: Mastectomy is the most common surgical procedure for breast cancer in low- and middle-income countries. Following mastectomy, patients usually require a drain to be inserted to prevent seroma formation. Several strategies are used to reduce the both the quantity of effluent and the duration a patient has to have the drain inserted. Methods: We did a prospective trial where patients were randomized to either use of quilting with 2-0 vicryl sutures or lack of quilting in order to reduce the post operative drain volume and the post operative period during which the drain will be in situ. Consecutive patients who are scheduled for mastectomy were randomized to either quilting or non-quilting of the skin to the pectoralis muscle. Duration of surgery was recorded. Consecutive daily volumes of drain effluent were documented until removal of the drain. Number of days before drain removal as well as body mass index and other parameters were recorded. Results: A total of 63 patients were recruited. Forty patients were randomized to non-quilting whilst 23 patients were randomized to quilting. The demographic data, stage of the disease and body mass index of the patients in the two categories were similar. The age range was 22 to 82 years. With mean age of 49.8 and median age of 48 years. The number of days before removal of drain ranged from 3 to 10 days with mean of 6.62 days and mode of 6 days. Mean daily drain effluent was 55 to 237mls with a mean of 134.5mls and median of 136mls while total drain effluent ranged between 166 to 2,173mls with mean of 938.1mls and median of 846 mls. Independent t-test revealed that there was a statistically significant difference in duration of drain insertion, mean daily drain effluent and total drain effluent between the two groups. There was however no statistically significant difference in the duration of surgery between the two groups. Conclusion: It is recommended that surgeons should quilt between the skin and pectoralis muscle in order to reduce the duration of drain insertion, daily drain effluent and total drain effluent following mastectomy in patients with breast cancer. Citation Format: AbdulRazzaq O. Lawal, Jimoh O. Hassan, Adewumi Alabi, Oluwole A. Atoyebi. Quilting of flaps reduces drain effluent without significantly increasing duration of surgery in mastectomy a low resource setting [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 4521.
Increased risk of hepatocellular carcinoma in HBeAg-negative indeterminate phase compared to HBeAg-negative chronic infection
Authors: Vicki Wing-Ki Hui, Grace Lai-Hung Wong, Junlong Dai, Yee-Kit Tse, Mandy Sze-Man Lai, Jimmy Che-To Lai, Henry Lik-Yuen Chan, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip
Journal: Hepatology (2025)

Background &amp; Aims: The outcomes and benefits of antiviral therapy in patients with indeterminate phase HBeAg-negative chronic hepatitis B (CHB) are not well described in treatment guidelines. We examined hepatocellular carcinoma (HCC) risk among these patients. Approach &amp; Results: We identified all non-cirrhotic treatment-naïve patients with HBeAg-negative CHB who received ≥1 test for hepatitis B virus (HBV) DNA and HBeAg. HBeAg-negative indeterminate phase included abnormal alanine aminotransferase (ALT ≥40 IU/L) and low HBV DNA (&lt;2,000 IU/mL), or normal ALT (&lt;40 IU/L) and high HBV DNA (≥2,000 IU/mL). Cox model evaluated relationship between HBV phase and HCC risk, with antiviral therapy as time-dependent variable. In 17,287 patients (mean age 54.1 years, 50% male), 4,071 (24%) transitioned to HBeAg-negative chronic hepatitis, 8,722 (50%) remained in the indeterminate phase, and 4,494 (26%) moved to HBeAg-negative chronic infection over a median follow-up of 55.1 [interquartile range 21.3-105.4] months. Patients in the indeterminate phase had a significantly higher HCC risk than those in chronic infection (adjusted hazard ratio [aHR] 1.587, 95% CI 1.262-1.995). Among patients in the indeterminate phase, those with normal ALT and high HBV DNA had a higher HCC risk than those with abnormal ALT and low HBV DNA (aHR 1.377, 95% CI 1.007-1.883, p =0.045). The 5-year cumulative HCC incidence showed no significant difference between treated and untreated patients in either group. Conclusions: In patients with indeterminate phase HBeAg-negative CHB, those with normal ALT and high HBV DNA showed a higher HCC risk than those with abnormal ALT and low HBV DNA, with no difference between treated and untreated patients in either group. Close monitoring with timely antiviral treatment may suffice to mitigate HCC risk in untreated patients.
Abstract 5933: Improved identification of lung neuroendocrine neoplasms using INSM1 (SP493) Rabbit Monoclonal Primary Antibody
Authors: Katerina Dvorak, Rafael Sainz, Alexander Gomez
Journal: Cancer Research (2025)

Abstract Introduction: About 20% of lung cancers are of neuroendocrine origin. In addition to evaluation of morphological features, these neoplasms can be identified by immunohistochemistry (IHC) using neuroendocrine markers such as synaptophysin, chromogranin A and neural cell adhesion molecule, CD56. Recent studies showed that INSM1 is increasingly used as a diagnostic marker for cancers of neuroendocrine origin, since it is highly sensitive and specific. The primary focus of this study was to assess the sensitivity and specificity of a newly developed assay that is using a new INSM1 (SP493) antibody in detecting neuroendocrine lung cancers and to compare this IHC assay with currently used neuroendocrine markers. Method: Tissue microarrays containing 292 lung tumors were stained with INSM1 (SP493) antibody, INSM1 (MRQ-70) antibody, CONFIRM anti-Synaptophysin (SP11) antibody, anti-Chromogranin A (LK2H10) antibody, and CD56 (MRQ-42) antibody on a BenchMark ULTRA instrument using OptiView DAB IHC Detection Kit or ultraView Universal DAB Detection Kit and sensitivity and specificity was calculated for each biomarker. Results: The sensitivity and specificity of this new assay with INSM1 (SP493) antibody were 92.5% and 95.8%, respectively. Similar results were obtained for the lung cancer cases stained with INSM1 (MRQ-70) antibody; the specificity was 90.6% and sensitivity was 95.9%. In contrast, anti-Synaptophysin (SP11) antibody and anti-Chromogranin A (LK2H10) antibody demonstrated considerably lower sensitivity when used to stain these lung cancer cases. The sensitivity was 79.7% and 75.8% for anti-Synaptophysin (SP11) antibody and anti-Chromogranin A (LK2H10) antibody, respectively. The specificity of anti-Chromogranin A (LK2H10) antibody was comparable with the specificity of the INSM1 (SP493) antibody (97.5%); while the specificity of anti-Synaptophysin (SP11) antibody was lower (90.8%). The performance of CD56 (MRQ-42) antibody was suboptimal with the sensitivity of 86.2% and the specificity of 84.9%. Conclusions: Overall, our data showed that the new IHC assay with INSM1 (SP493) antibody is highly specific and sensitive in detecting neuroendocrine lung tumors. Citation Format: Katerina Dvorak, Rafael Sainz, Alexander Gomez. Improved identification of lung neuroendocrine neoplasms using INSM1 (SP493) Rabbit Monoclonal Primary Antibody [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 5933.
Abstract 4651: Long non coding RNA LINC01224 is prognostic marker and regulates cancer stemness in the NSCLC
Authors: Ji Woong Son, Wan Jin Hwang, Minhyeok Lee, Daeun Kang, In Beom Jeong, Sun Jung Kwon
Journal: Cancer Research (2025)

Abstract Long noncoding RNA is also a molecule that is attracting attention these days. Only about 1.5% of the genome is protein-coding, while the other 98.5% consists of non-coding elements, which are transcribed by RNA polymerase II (polII) into non-coding RNA (ncRNA). Among them, ncRNAs with a size of 200nt or more are called long non-coding RNAs (lncRNAs). To date, lncRNA have been recognized to have regulatory roles in gene expression through various mechanisms. They are involved in diverse biological processes such as cell differentiation, apoptosis, development, inflammatory response, and immune response. Cancer stem cells (CSCs) identified in lung cancer exhibit resistance to chemotherapy, radiotherapy, and targeted therapy. Therefore, a technology for controlling CSCs is needed to overcome such resistance to cancer therapy. The authors planned this study to discover lncRNAs involved in cancer stemness. We analyzed TCGA data to search for lncRNAs that predict the prognosis of NSCLC and selected LINC01224 as a candidate lncRNA involved in cancer stemness. Treatment of LINC01224 with siRNA reduced colony formation ability in cell lines with stem cell characteristics. Next, we performed whole-genome expression in lung cancer cell line after siRNA treatment to identify gene controlled by LINC01224. This experiment revealed that lncRNA is involved in apoptosis, cell cycle, cell death, cell differentiation, cell migration, and DNA repair. LINC01224 is a prognostic factor and an attractive treatment target for non-small cell lung cancer. LINC01224 possibly regulates various biological phenomena and specific mechanism studies are needed. Citation Format: Ji Woong Son, Wan Jin Hwang, Minhyeok Lee, Daeun Kang, In Beom Jeong, Sun Jung Kwon. Long non coding RNA LINC01224 is prognostic marker and regulates cancer stemness in the NSCLC [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 4651.
Abstract 4634: Development of novel monoclonal antibody detection of ERα36 in breast cancer
Authors: Alexandra C. Selico Dunn, Hogyoung Kim, DeZha A. Robinson, Sihyoung Kim, Clark J. Perkins, Sichan Kim, Emily L. Smith, Emma Elkins, Christopher Williams
Journal: Cancer Research (2025)

Abstract Approximately 75% of breast cancer tumors express the estrogen receptor alpha steroid receptor. Canonical estrogen receptors ERα66 and ERβ1 are the main mediators of estrogen-dependent pathophysiology in mammals. However, numerous isoforms have been identified, stimulating unconventional estrogen response pathways leading to complex cellular and tissue responses. Estrogen receptor alpha plays essential roles in the human body, such as the reproductive organs and metabolic and inflammatory systems. Recent studies suggest that a 36 kD variant of ERα (ERα36, ERα isoform 4) may play a role in endocrine therapy resistance in breast carcinoma (BCa). However, a key limitation to discovering the precise role of ERα36 in BCa is the lack of reliable, commercially available antibodies. Most ERα polyclonal antibodies show poor antigen specificity, hindering the evaluation of ERα36 as a clinical biomarker in BCa. Our goal is to develop a reliable monoclonal antibody targeting ERα36, which could facilitate its development as a clinical biomarker in BCa. Here, we describe the development of hybridoma producing an ERα36 monoclonal antibody (34F11) followed by rigorous enrichment (ultrafiltration), purification (fast protein liquid chromatography), and affinity (spectral shift assay) characterization. We assessed the utility of 34F11 antibody in several applications (immunoblot, immunohistochemistry, and fluorescence cytometry). Here, we provide the first comparative characterization of a monoclonal antibody directed toward ERα36 for the potential implementation of biomarker detection in BCa. Citation Format: Alexandra C. Selico Dunn, Hogyoung Kim, DeZha A. Robinson, Sihyoung Kim, Clark J. Perkins, Sichan Kim, Emily L. Smith, Emma Elkins, Christopher Williams. Development of novel monoclonal antibody detection of ERα36 in breast 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 4634.