tbuckley/cabot-search huggingface dataset:
Breaking the Itch Cycle: Long-Term effects of Nemolizumab in Prurigo Nodularis
Authors: Kamila Kędra, Adam Reich
Journal: British Journal of Dermatology (2025)

Journal Article Accepted manuscript Breaking the Itch Cycle: Long-Term effects of Nemolizumab in Prurigo Nodularis Get access Kamila Kędra, Kamila Kędra Department of Dermatology, Medical Faculty, Medical College of Rzeszów University, 35-055 Rzeszów, PolandRzeszów University Doctoral School, 35-959 Rzeszów, Poland Search for other works by this author on: Oxford Academic Google Scholar Adam Reich Adam Reich Department of Dermatology, Medical Faculty, Medical College of Rzeszów University, 35-055 Rzeszów, Poland Correspondence: Adam Reich, Email: [email protected] Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljaf093, https://doi.org/10.1093/bjd/ljaf093 Published: 11 March 2025 Article history Received: 09 March 2025 Accepted: 10 March 2025 Published: 11 March 2025
Do manuscripts by female evolutionary biologists spend longer under review?
Authors: David Alvarez-Ponce, James Vesper
Journal: Molecular Biology and Evolution (2025)

Abstract Women are underrepresented in academia and in STEM careers, especially at senior positions and top institutions. This may be, at least in part, due to the many obstacles that they experience along the academic pipeline. There has been substantial debate as to whether women are treated unfairly during the peer review process. An analysis of over 9000 research articles published in top Economics journals has recently shown that female-authored articles tend to spend 3-6 months longer under review (period from submission to acceptance), and to have more readable abstracts, than male-authored articles, suggesting that female-authored articles are held to higher standards. We set out to determine whether these trends were also present among 49,031 papers published in 11 Evolutionary Biology journals. We found that female representation among article authors substantially increased over the decades. The percentage of women is lower among corresponding authors than among all authors, especially of recent articles. In addition, female first authors were less likely to be corresponding authors than male first authors, and the gender of the first author correlated with the gender of the corresponding author. In some of the journals, female-authored articles spent significantly longer under review; however, most of the observed differences vanish after controlling for the date of publication and the number of authors. In addition, female-authored abstracts are not more readable. Our results suggest that the peer review process in the field of Evolutionary Biology is generally not biased against women.
Rapid improvements in Kaposi sarcoma with metformin: a report of two cases
Authors: Ting Su, Yongkai Yu, Zhonglan Su, Yan Lu
Journal: British Journal of Dermatology (2025)

This report details interesting, positive, and perhaps somewhat surprising outcomes following the administration of metformin—typically used to treat type 2 diabetes - to two older male patients with Kaposi sarcoma. As an antidiabetic agent, metformin decreases blood sugar, cholesterol, and triglyceride levels, and activates the AMPK/mTOR pathway to inhibit cell metabolism, proliferation, and angiogenesis. We believe that our study makes a significant contribution to the literature because metformin is generally accessible, well-tolerated, and has been shown to have a wide range of effects that may make it a promising therapy not only for diabetes, but also for cancers such as Kaposi sarcoma—particularly in more resource-limited settings such as developing countries.
Linear hypermelanosis in narrow bands, a mosaic pattern manifestation of dyskeratosis congenita?
Authors: Ran Mo, Mingming Xu, Zhiming Chen, Ruiyu Xiang, Xiaofang Li, Hongyang Li, Guoyi Zhang, Jianfang Sun, Wei Zhang, Yong Yang
Journal: British Journal of Dermatology (2025)

Our research investigates two cases involving the TINF2 gene variant (c.844C&amp;gt;T), demonstrating distinct phenotypes of classic dyskeratosis congenita (DC) and a novel linear hypermelanosis in narrow bands like mosaic DC. The first patient presented with classic DC features linked to a germline mutation, while the second exhibited extensive linear hypermelanosis in narrow bands like pigmentary lesions attributed to somatic mosaicism. These findings underscore the critical role of genetic analysis, particularly in affected tissues, for understanding mosaic dermatoses. It also expand the phenotypic spectrum of DC and shed light on the molecular mechanisms underlying mosaic congenital dyschromatosis.
Abstract IA007: Rapid ex vivo biosensor cultures to assess dependencies in gastroesophageal cancer
Authors: Jesse S Boehm, Mushriq Al-Jazrawe, Csaba Molnar, Beth Cimini, Samuel Klempner, Niklas Rindtorff, Steven Blum
Journal: Cancer Research (2025)

Abstract Overcoming cancer drug resistance is a major unmet clinical need as it remains challenging to accurately predict therapeutic sensitivity from baseline tumor and immune profiling. While biopsies from refractory disease are challenging to routinely obtain for research, upwards of 40% of gastroesophageal and 70% ovarian patients develop peritoneal carcinomatosis and ascites, a plentiful, heterogenous and molecularly representative sample format that is easily accessible since routine drains occur. However, in standard clinical practice this material is only subjected to cytology to detect malignant cells and then discarded. Bulk profiling technologies are challenging to deploy due to the highly variable single cell heterogeneity of ascites. To address these challenges, we have generated the first generation of AscitesPredict, an ‘ex vivo tumor biosensor’ technology using single cell technologies to measure cell identities and therapeutic sensitivities during a 5 day period in which viability is preserved via media supplementation with patient-matched ascites fluid. AscitesPredict utilizes high dimensional single cell image-based morphological profiling and machine learning applied to brightfield microscopy. Thus far, we have profiled over 40 GEA ascites samples, made initial assessments of technological reproducibility, and have optimized initial workflows. Our ultimate goal is to harden the technology to facilitate deployment by a wide diversity of researchers and clinicians for two driving use cases: (1) supporting preclinical drug development and (2) eventually as a functional diagnostic. Citation Format: Jesse S Boehm, Mushriq Al-Jazrawe, Csaba Molnar, Beth Cimini, Samuel Klempner, Niklas Rindtorff, Steven Blum. Rapid ex vivo biosensor cultures to assess dependencies in gastroesophageal cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr IA007.
Abstract IA002: Functional omics for novel therapeutic combinations in myeloid malignancies
Authors: Jeffrey W Tyner
Journal: Cancer Research (2025)

Abstract My research program employs a pipeline of functional approaches for analysis of primary cells from patients with acute myeloid leukemia (AML) and other hematologic malignancies. This platform aims to identify the druggable landscape across hematologic malignancies and prioritize novel combination therapies. The pipeline is comprised of gene knockdown (e.g. siRNA, CRISPR/Cas) and small-molecule libraries to interrogate the genes, pathways, cellular processes, and microenvironmental crosstalk that govern cancer cell growth and drug response, and these functional screens are complemented with deep sequencing. Simultaneous application of these functional approaches with omic data has accelerated our understanding of druggable pathways that contribute to neoplasia. One example of this platform has been our Beat AML 1.0 platform in which we have assessed ex vivo drug sensitivity, whole exome sequencing, and RNA-sequencing for a cohort of nearly 1,000 AML patient samples, which provides a functional genomic landscape for this disease. We have also utilized genome-wide CRISPR screens with overlay of key therapeutic agents in cell line models, and coupling of these genome-wide screen data with the large patient sample dataset has illuminated a diversity of determinants of therapeutic response. In this lecture, I will provide an overview of these functional screening platforms, and I will illustrate strategies of data integration that have enabled rapid discovery and translation of new targeted therapy strategies. This will include discussion of novel biomarkers of drug response in AML, including mutational drivers of drug response and strong correlation of AML tumor cell maturation state with response to a diversity of drugs and drug families. Finally, the lecture will provide examples of the way in which these data can be leveraged to identify novel drug combinations with broad activity and to examine the mechanistic underpinnings of improved combination activity relative to single agents. Collectively, this dataset and integrative approach provide a functional genomic landscape of AML with new biomarkers of drug response. Citation Format: Jeffrey W Tyner. Functional omics for novel therapeutic combinations in myeloid malignancies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr IA002.
Abstract IA003: Integrated consideration of constitutional and somatic genetic features to improve knowledge and care of AML patients
Authors: Ann-Kathrin Eisfeld
Journal: Cancer Research (2025)

Abstract Our knowledge of the genomics of acute myeloid leukemia (AML), which serves as the basis of clinically used prognostic biomarkers and therapeutic advances (including targeted therapies), is almost exclusively based on data from patients of European ancestry. However, recent research efforts uncovered differences in somatic mutation frequencies in AML patients with respect to genetic ancestry, as well as differences in their previously established prognostic impact when referring to response to standard of care chemotherapy. Together, this strongly suggests the importance to consider differences in the constitutional genetic background and their direct or indirect effects on somatic genomic features. We will discuss interconnected contributors to survival disparities especially of non Hispanic (NH)-Black patients with AML, highlighting social contributors, trial enrollment and structural racism. We will highlight the diverse genetic and genomic landscape of patients with AML, including the identification of several recurrent gene mutations thus far not established in AML identified in NH-Black patients. We will highlight differences in immune response patterns that may affect the observed phenotypes, including both coding and non-coding RNAs. Importantly, we will show examples of how this new information derived from a more inclusive patient population is able to refine the disease biology of all AML patients. Lastly, there will be insights into differential prognostic impact of gene mutations, including biologic rationales for the observed ancestry-associated effects via comprehensive, multi-omic single cell sequencing studies; that strongly suggest the need to consider genetic ancestry in clinically used prognostic risk assignments. Citation Format: Ann-Kathrin Eisfeld. Integrated consideration of constitutional and somatic genetic features to improve knowledge and care of AML patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr IA003.
Abstract A015: Unlocking therapeutic potential of rigosertib as a selective therapy for ovarian cancer
Authors: SHALINI NATH, Sally Claridge, Genesis Lara Granados, Majd Al Assaad, Eric Park, Julie-Ann Cavallo, Maame Esi Ackon, Lamberto De Boni, Stacey Baker, E. Premkumar Reddy, Stephanie V Blank, Olivier Elemento, Rachel Brody, Benjamin D. Hopkins
Journal: Cancer Research (2025)

Abstract Ovarian cancer has a devastating impact. In 2024 it is estimated that there will be 19,680 new ovarian cancer diagnoses and 12,740 fatalities in the United States. Despite advancements in treatment options, 80% of ovarian tumors recur or progress through treatments leading to a five year survival rate of just 50%. To address this unmet need, we employed a functional genomics approach to identify ovarian cancer specific drug sensitivities. Comparing the impact of each of the 117 drugs in our library across 32 cancer cell lines from 11 tumor lineages we identified Rigosertib, a small molecule RAS mimetic, as a selective agent for treatment of ovarian cancer. This ovarian cancer specific sensitivity to Rigosertib was validated in a panel of ovarian cancer cell lines and patient-derived organoids. This sensitivity fits with the observation that ovarian cancer exhibits a high frequency of alterations in both the PI3K and MAPK pathways, both of which can be negatively regulated through the disruption of RAS interactions. Concordantly, while the interplay between these pathways creates an inverse regulatory relationship by which inhibition of either pathway can lead to activation of the other, we observe that in all of the ovarian lines tested that treatment with Rigosertib leads to increases of MTOR signaling as indicated by phosphorylation of S6 both in vitro and in vivo. Subsequent combination drug screening revealed a cooperative effect between rigosertib and PI3K inhibitor (taselisib), suggesting that combining rigosertib with taselisib which restricts mTOR activation enhances therapeutic efficacy. This combination showed synergy across ovarian cancer cell lines, organoids, and xenograft models, with xenograft studies showing a significant reduction in tumor burden. These findings highlight the potential of rigosertib, especially when paired with PI3K inhibitors, to target the unique mutational landscape of ovarian cancer, offering a promising direction for more effective treatments. Citation Format: SHALINI NATH, Sally Claridge, Genesis Lara Granados, Majd Al Assaad, Eric Park, Julie-Ann Cavallo, Maame Esi Ackon, Lamberto De Boni, Stacey Baker, E. Premkumar Reddy, Stephanie V Blank, Olivier Elemento, Rachel Brody, Benjamin D. Hopkins. Unlocking therapeutic potential of rigosertib as a selective therapy for ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr A015.
Abstract IA030: Harnessing patient biopsies and AI for rapid, personalized cancer therapy discovery
Authors: Taran Gujral
Journal: Cancer Research (2025)

Abstract Timely and precise identification of effective treatments is crucial for improving patient outcomes and reducing healthcare costs, particularly in cancer care. This challenge is amplified in rare, recurrent, and hard-to-treat cancers due to their genetic complexity and tumor heterogeneity. Dr. Gujral will discuss his lab’s innovative approach to revolutionize cancer treatment through the development of a clinically integrated, data-driven platform for predicting drug responses. By analyzing patient biopsy samples collected within hours of surgery and applying advanced artificial intelligence algorithms, this platform rapidly screens thousands of potential therapies, delivering actionable insights in under a week. The goal is to bring this system into everyday medical care, making cancer treatment faster, more effective, and more affordable for everyone. Citation Format: Taran Gujral. Harnessing patient biopsies and AI for rapid, personalized cancer therapy discovery [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr IA030.
Abstract IA036: Using cancer stem cells to advance functional medicine in the era of precision oncology
Authors: Pier Paolo Claudio, Candace M Howard
Journal: Cancer Research (2025)

Abstract Functional precision medicine (FPM) is a new approach in oncology that uses advanced technologies to personalize anticancer treatments based on the dynamic, functional characteristics of a patient's cancer at the molecular and cellular levels. Unlike traditional precision medicine, which often focuses on genomic information alone, FPM emphasizes the use of functional assays, such as cellular response profiling, to assess how a patient’s cancer reacts to various therapeutic agents in real time. This approach aims to bridge the gap between genetic susceptibilities and treatment outcomes, providing more accurate predictions of treatment efficacy and improving clinical decision-making. The utilization of functional diagnostic assays, such as the ChemoID assay, further enhances the potential of FPM. By directly assessing drug efficacy in patient-derived cancer stem cells (CSCs), the ChemoID assay provides crucial insights into tumor behavior and treatment resistance. The clinical validation of this assay in phase-3 randomized trials for glioblastoma and platinum-resistant ovarian cancer underscores its potential to significantly improve patient outcomes, particularly in cases where standard treatments have failed. The integration of functional assays like ChemoID into clinical trial designs represents a significant step forward in personalized cancer treatment. By bridging the gap between genomic information and treatment outcomes, this approach has the potential to transform the clinical management of cancer and improve the lives of patients. Clinical efficacy data from ChemoID randomized trials will be presented. Citation Format: Pier Paolo Claudio, Candace M Howard. Using cancer stem cells to advance functional medicine in the era of precision oncology [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr IA036.
Abstract B011: Harnessing epigenetic and metabolic biomarkers for targeted immunotherapy in colorectal cancer: Advances in precision medicine for solid tumors
Authors: Ji Min Lee
Journal: Cancer Research (2025)

Abstract Cancer cells are defined by rapid, unchecked proliferation, a hallmark that distinguishes them from normal cells. This aggressive growth often leads to a nutrient- and oxygen-deprived tumor core, where limited blood supply cannot sufficiently reach. While most cells typically undergo cell death under such glutamine-deficient conditions, a subset of cancer cells survives through specific epigenetic modifications, facilitating metastatic progression. Using spatial transcriptomics analysis, we reveal that colorectal cancer cells exploit the downregulation of GLS2 expression to avoid ferroptosis and support metastasis in the tumor's glutamine-starved core. We further identified an increase in H3K27Me3 modification as a key epigenetic driver enabling these adaptations in glutamine-deficient regions. This hypothesis has been validated in in vivo mouse colon cancer models and in patient samples compared with healthy controls, reinforcing its translational relevance. Importantly, by employing amino acid profiling through 19F NMR spectroscopy, we identified key biomarkers in the tumor microenvironment that may enhance response to immunotherapy and overcome current therapeutic resistance. These findings underscore the potential of precision medicine strategies that target ferroptosis, epigenetic regulation, and tumor-specific biomarkers, offering new avenues for therapeutic intervention in colorectal cancer patients, particularly those with core-originating tumor regions. Our work exemplifies the broader goal of functional and genomic precision medicine in cancer, aligning distinct mechanistic insights with shared therapeutic objectives. Citation Format: Ji Min Lee. Harnessing epigenetic and metabolic biomarkers for targeted immunotherapy in colorectal cancer: Advances in precision medicine for solid tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr B011.
Abstract IA026: Pan-cancer <i>N</i>-glycoproteomic atlas of patient-derived xenografts uncovers FAT2 as a therapeutic target for head and neck cancers
Authors: Thomas Kislinger
Journal: Cancer Research (2025)

Abstract Cell surface proteins offer significant cancer therapeutic potential attributable to their accessible membrane localization and central role in cellular signaling. Despite this, their promise remains largely untapped due to the technical challenges inherent to profiling cell surface proteins. Here, we employed N-glycoproteomics to analyze 85 patient-derived xenografts (PDX), constructing Glyco PDXplorer – an in vivo pan-cancer atlas of cancer-derived cell surface proteins. We developed a target discovery pipeline to prioritize proteins with favorable expression profiles for immunotherapeutic targeting and validated FAT2 as a head and neck squamous cancer (HNSC) enriched surface protein with limited expression in normal tissue. Functional studies revealed that FAT2 is essential for HNSC growth and adhesion through regulation of surface architecture and integrin-PI3K signaling. Chimeric antigen receptor (CAR) T cells targeting FAT2 demonstrated potent anti-tumor activity in HNSC models. This work lays the foundation for developing FAT2-targeted therapies and represents a pivotal resource to inform therapeutic target discovery for multiple cancers. Citation Format: Thomas Kislinger. Pan-cancer N-glycoproteomic atlas of patient-derived xenografts uncovers FAT2 as a therapeutic target for head and neck cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr IA026.