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Mashup Score: 4
Abstract. The intersection of precision medicine and artificial intelligence (AI) holds profound implications for cancer treatment, with the potential to significantly advance our understanding of drug responses based on the intricate architecture of tumor cells. A recent study by Park and colleagues titled
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Mashup Score: 13
Abstract. Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress-response programs that counteract the inherent toxicity of such aberrant signaling. While inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of Protein Phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data s
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Mashup Score: 0OnlineFirst - 28 day(s) ago
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Mashup Score: 1OnlineFirst - 1 month(s) ago
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Mashup Score: 1
Abstract. Serine metabolism plays a pivotal role in cancer, making it an appealing therapeutic target. Two recent studies published in Nature Metabolism and Science Translational Medicine uncovered novel players and therapeutic opportunities within this crucial metabolic pathway. Papalazarou and colleagues employed genetic tools coupled with metabolomics and high-throughput imaging to identify and characterize membrane transporters involved in serine uptake and mitochondrial import in colorectal cancer. Notably, they showed that dual inhibition of these transporters in combination with impaired serine biosynthesis reduced tumor growth in xenograft models. In a parallel study, Zhang and colleagues identified isocitrate dehydrogenase I (IDH1) as a novel regulator of serine biosynthesis in non-small cell lung cancer (NSCLC). Through extensive mechanistic studies, they demonstrated that IDH1 enhances the expression of the key enzymes phosphoglycerate dehydrogenase (PHGDH) and phosphoserine
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Mashup Score: 17Deep Learning Model for Tumor Type Prediction using Targeted Clinical Genomic Sequencing Data - 2 month(s) ago
Abstract. Tumor type guides clinical treatment decisions in cancer, but histology-based diagnosis remains challenging. Genomic alterations are highly diagnostic of tumor type, and tumor type classifiers trained on genomic features have been explored, but the most accurate methods are not clinically feasible, relying on features derived from whole genome sequencing (WGS), or predicting across limited cancer types. We use genomic features from a dataset of 39,787 solid tumors sequenced using a clinical targeted cancer gene panel to develop Genome-Derived-Diagnosis Ensemble (GDD-ENS): a hyperparameter ensemble for classifying tumor type using deep neural networks. GDD-ENS achieves 93% accuracy for high-confidence predictions across 38 cancer types, rivalling performance of WGS-based methods. GDD-ENS can also guide diagnoses on rare type and cancers of unknown primary, and incorporate patient-specific clinical information for improved predictions. Overall, integrating GDD-ENS into prospect
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Mashup Score: 11Adding new dimensions to 3D cancer models - 2 month(s) ago
Abstract. Understanding patient-specific responses to anti-cancer therapies and how individual tumors interact with their tumor microenvironment (TME) is a challenging task. To measure the impact of the TME on diverse and clinically-relevant treatments, Zapatero, Tong, and colleagues coupled patient-derived organoid (PDO) and cancer-associated fibroblast (CAF) co-cultures with high-throughput mass cytometry-based assessment of cell state. Using a newly developed
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Mashup Score: 0Integrated Proteogenomics Uncover Mechanisms of Glioblastoma Evolution, Pointing to Novel Therapeutic Targets. - 2 month(s) ago
Abstract. Nearly all glioblastoma (GBM) patients relapse following standard treatment and eventually succumb to disease. While large scale, integrated multi-omic studies have tremendously advanced the understanding of primary GBM at the cellular and molecular level, the post-therapeutic trajectory and biological properties of recurrent GBM remain poorly understood. This knowledge gap was addressed in a recent Cancer Cell article in which Kim and colleagues report on a highly integrative proteogenomic analysis performed on 123 matched primary and recurrent GBMs that uncovered a dramatic evolutionary shift from a proliferative state at initial diagnosis to the activation of neuronal and synaptogenic pathways at recurrence following therapy. Neuronal transition was characterized by post-translational activation of WNT/PCP signaling and BRAF kinase, while many canonical oncogenic pathways, and EGFR in particular, were downregulated. Parallel multi-omics analyses of patient-derived xenograf
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Mashup Score: 18A metabolic-epigenetic mechanism directs cell fate and therapeutic sensitivity in breast cancer - 2 month(s) ago
Abstract. Over the past decade, studies have increasingly shed light on a reciprocal relationship between cellular metabolism and cell fate, meaning that a cell’s lineage both drives and is governed by its specific metabolic features. A recent study by Zhang and colleagues, published in Cell Metabolism, describes a novel metabolic-epigenetic regulatory axis that governs lineage identity in triple negative breast cancer (TNBC). Among the key findings, the authors demonstrate that the metabolic enzyme pyruvate kinase M2 (PKM2) directly binds to the histone methyltransferase enhancer of zeste homologue 2 (EZH2) in the nucleus to silence expression of a set of genes that includes the mitochondrial carnitine transporter SLC16A9. Perturbation of this metabolic-epigenetic regulatory mechanism induces a metabolic shift away from glycolysis and towards fatty acid oxidation. The ensuing influx of carnitine facilitates the deposition of the activating epigenetic mark H3K27Ac onto the promoter of
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Mashup Score: 1
Abstract. Colorectal cancer (CRC) is a prevalent cancer type in the United States, affecting both genders and influenced by genetics and environmental factors. The role of the gut microbiome in CRC development and therapy response is a burgeoning field of study. A recent study uncovered that trans-3-indoleacrylic acid (IDA), a microbial metabolite from P. anaerobius, promotes CRC by inhibiting ferroptosis, a type of non-apoptotic cell death driven by unrestricted lipid peroxidation and subsequent membrane damage. IDA activates aryl hydrocarbon receptor (AHR), a nuclear transcription factor, leading to the expression of aldehyde dehydrogenase 1 family member A3 (ALDH1A3). ALDH1A3, known for aldehyde detoxification, also contributes to ferroptosis resistance by generating reduced nicotinamide adenine dinucleotide (NADH), critical for the synthesis of reduced coenzyme Q10 (COQH10) by apoptosis inducing factor mitochondria associated 2 (AIFM2, also known as FSP1). Knocking out AHR, AIFM2,
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#OnlineFirst: Read the In the Spotlight commentary, How AI Unravels the Complex Web of Cancer Drug Response, by @ElementoLab discussing a recent @NatureCancer paper from @TreyIdeker et al. https://t.co/z1KLxvaZP0 https://t.co/NzaUYAxuiC