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Mashup Score: 57The extracellular niche and tumor microenvironment enhance KRAS inhibitor efficacy in pancreatic cancer. - 4 month(s) ago
Abstract. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that lacks effective treatment options, highlighting the need for developing new therapeutic interventions. Here, we assessed the response to pharmacological inhibition of KRAS, the central oncogenic driver of PDAC. In a panel of PDAC cell lines, inhibition of KRASG12D with MRTX1133 yielded variable efficacy in suppressing cell growth and downstream gene expression programs in 2D cultures. Based on CRISPR-Cas9 loss-of-function screens, ITGB1 was identified as a target to enhance the therapeutic response to MRTX1133 by regulating mechanotransduction signaling and YAP/TAZ expression, which was confirmed by gene specific knockdown and combinatorial drug synergy. Interestingly, MRTX1133 was considerably more efficacious in 3D cell cultures. Moreover, MRTX1133 elicited a pronounced cytostatic effect in vivo and controlled tumor growth in PDAC patient-derived xenografts. In syngeneic models, KRASG12D inhibition led to
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 73The Molecular Twin artificial-intelligence platform integrates multi-omic data to predict outcomes for pancreatic adenocarcinoma patients - 4 month(s) ago
Nature Cancer – Theodorescu and colleagues describe a Molecular Twin approach that integrates multi-omic and computational pathology data from patients with pancreatic ductal adenocarcinoma using…
Source: www.nature.comCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 73The Molecular Twin artificial-intelligence platform integrates multi-omic data to predict outcomes for pancreatic adenocarcinoma patients - 4 month(s) ago
Nature Cancer – Theodorescu and colleagues describe a Molecular Twin approach that integrates multi-omic and computational pathology data from patients with pancreatic ductal adenocarcinoma using…
Source: www.nature.comCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 47Autotaxin–lysolipid signaling suppresses a CCL11–eosinophil axis to promote pancreatic cancer progression - 4 month(s) ago
Nature Cancer – Sherman and colleagues show that ATX suppresses the accumulation of eosinophils in the tumor microenvironment of pancreatic cancer via suppression of CCL11 expression and find that…
Source: www.nature.comCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 46Autotaxin–lysolipid signaling suppresses a CCL11–eosinophil axis to promote pancreatic cancer progression - 4 month(s) ago
Nature Cancer – Sherman and colleagues show that ATX suppresses the accumulation of eosinophils in the tumor microenvironment of pancreatic cancer via suppression of CCL11 expression and find that…
Source: www.nature.comCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 52Pancreatic Cancer Action Network's SPARK: A Cloud-Based Patient Health Data and Analytics Platform for Pancreatic Cancer - 5 month(s) ago
PURPOSE Pancreatic cancer currently holds the position of third deadliest cancer in the United States and the 5-year survival rate is among the lowest for major cancers at just 12%. Thus, continued research efforts to better understand the clinical and molecular underpinnings of pancreatic cancer are critical to developing both early detection methodologies as well as improved therapeutic options. This study introduces Pancreatic Cancer Action Network’s (PanCAN’s) SPARK, a cloud-based data and analytics platform that integrates patient health data from the PanCAN’s research initiatives and aims to accelerate pancreatic cancer research by making real-world patient health data and analysis tools easier to access and use. MATERIALS AND METHODS The SPARK platform integrates clinical, molecular, multiomic, imaging, and patient-reported data generated from PanCAN’s research initiatives. The platform is built on a cloud-based infrastructure powered by Velsera. Cohort exploration and browser c
Source: ascopubs.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 36Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1 - 5 month(s) ago
Activation of distinct myeloid signaling pathways converges to overcome immune suppression in pancreatic cancer.
Source: www.science.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 39Advances in the management of pancreatic cancer - 5 month(s) ago
Pancreatic cancer remains among the malignancies with the worst outcomes. Survival has been improving, but at a slower rate than other cancers. Multimodal treatment, including chemotherapy, surgical resection, and radiotherapy, has been under investigation for many years. Because of the anatomical characteristics of the pancreas, more emphasis on treatment selection has been placed on local extension into major vessels. Recently, the development of more effective treatment regimens has opened up new treatment strategies, but urgent research questions have also become apparent. This review outlines the current management of pancreatic cancer, and the recent advances in its treatment. The review discusses future treatment pathways aimed at integrating novel findings of translational and clinical research.
Source: www.bmj.comCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 25Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1 - 6 month(s) ago
Activation of distinct myeloid signaling pathways converges to overcome immune suppression in pancreatic cancer.
Source: www.science.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 15Super-enhancer RNA m6A promotes local chromatin accessibility and oncogene transcription in pancreatic ductal adenocarcinoma - 6 month(s) ago
Nature Genetics – In pancreatic duct adenocarcinoma, super-enhancer RNAs (seRNAs) have higher N6-methyladenosine (m6A) levels than in adjacent normal tissue due to upregulation of the METTL3…
Source: www.nature.comCategories: General Medicine News, Hem/OncsTweet
Very interesting #OpenAccess preclinical study on MRTX1133 in @CR_AACR from @RoswellPark: The extracellular niche and tumor microenvironment enhance KRAS inhibitor efficacy in #PancreaticCancer https://t.co/EoPvjY1b6K The study uses a variety of patient derived & syngeneic… https://t.co/KdS8VpkWTe https://t.co/WN2LQSyRZF