Huda Jumaa

Immunomodulatory impact of PTPN11 /SHP2-based vertical RAS-MAPK pathway inhibition in pancreatic cancer

Asma Alrawashdeh, Xun Chen, Philipp Hafner, Steffen J. Keller et autres

Abstract Protein tyrosine phosphatase non-receptor 11 ( PTPN11 /SHP2) is a critical upstream mediator of RAS-MAPK signaling and a central node in adaptive resistance mechanisms evolving with RAS and MEK/ERK inhibition. Accordingly, clinical trials are currently evaluating allosteric SHP2 inhibitors in vertical …

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Membrane localisation and checkpoint blockade enhance xenoantigen delivery to redirect pre-existing immunity against tumours

Sylvie Hauert, Fuxin Zhou, Justas Šidiškis, Aishwarya Saxena et autres

ABSTRACT Cancer immunotherapies often rely on the recognition of tumour antigens, which strongly limits their efficacy upon heterogeneous antigen expression or downregulation. A strategy to overcome this limitation is to redirect pre-existing antiviral immunity against tumours through the delivery of xenoantigens. While …

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Vertical RAS pathway inhibition in pancreatic cancer drives therapeutically exploitable mitochondrial alterations

Philipp Hafner, S. Keller, Xun Chen, Asma Alrawashdeh et autres

Oncogenic KRAS mutations drive metabolic reprogramming in pancreatic ductal adenocarcinoma (PDAC). Src-homology 2 domain-containing phosphatase 2 (SHP2) is essential for full KRAS activity, and promising dual SHP2/mitogen-activated protein kinase (MAPK) inhibition is currently being tested in clinical trials. Exploitable metabolic adaptations may …

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Targeting β-catenin degradation with GSK3β inhibitors induces cell death in acute lymphoblastic leukemia

Kadriye Nehir Cosgun, Huda Jumaa, Mark E. Robinson, Zhangliang Cheng et autres

As part of canonical Wnt signaling, T cell factor (TCF)-β-catenin complexes promote MYC-dependent proliferation. Lesions of the β-catenin protein degradation machinery are common oncogenic drivers. Here, we show that B cell acute lymphoblastic leukemia (B-ALL) lacks these mutations and critically depends on …

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Vertical RAS-pathway inhibition in pancreatic cancer drives therapeutically exploitable mitochondrial alterations

Philipp Hafner, S. Keller, Xun Chen, Asma Alrawashdeh et autres

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Abstract B038: Vertical RAS-pathway inhibition in pancreatic cancer drives therapeutically exploitable mitochondrial alterations

Philipp Hafner, S. Keller, Xun Chen, Asma Alrawashdeh et autres

Abstract Oncogenic KRAS mutations drive metabolic rewiring in pancreatic ductal adenocarcinoma (PDAC). Src-homology 2 domain-containing phosphatase 2 (SHP2) is essential for full KRAS activity and promising dual SHP2/mitogen-activated protein kinase (MAPK) inhibition is currently being tested in clinical trials. Exploitable metabolic adaptations …

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Adaptive resistance to SHP2-based vertical RAS-pathway inhibition in pancreatic cancer involves multifaceted routes towards dedifferentiation

Xun Chen, S. Keller, Tonmoy Das, Philipp Hafner et autres

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) critically depends on oncogenic KRAS signaling. The Src-homology 2 domain-containing phosphatase 2 (SHP2) is essential for full KRAS activity. Allosteric SHP2 inhibition in vertical combination with mitogen-activated protein kinase (MAPK) or RAS inhibition demonstrates synergistic efficacy, …

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Vertical RAS-pathway inhibition in pancreatic cancer drives therapeutically exploitable mitochondrial alterations

Philipp Hafner, S. Keller, Xun Chen, Asma Alrawashdeh et autres

Abstract Background & Aims Oncogenic KRAS mutations drive metabolic rewiring in pancreatic ductal adenocarcinoma (PDAC). Src-homology 2 domain-containing phosphatase 2 (SHP2) is essential for full KRAS activity and promising dual SHP2/mitogen-activated protein kinase (MAPK) inhibition is currently being tested in clinical trials. …

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Impact of PTPN11/SHP2 +/- MEK Inhibition on the anti-tumor immune response in mutant KRAS driven PDAC

Asma Alrawashdeh, Huda Jumaa, Philipp Hafner, S. Keller et autres

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19Fluorine ‐ MRI Based Longitudinal Immuno‐Microenvironment‐Monitoring for Pancreatic Cancer

Wilfried Reichardt, Tabea Gewalt, Philipp Hafner, S. Keller et autres

Background Pancreatic cancer has a poor prognosis. Targeting Kirsten Rat Sarcoma (KRAS) mutation and its related pathways may enhance immunotherapy efficacy. While in vivo monitoring of therapeutic response and immune cell migration remains challenging, Fluorine‐19 MRI (19F MRI) may allow noninvasive longitudinal …

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Dependence of lymphopoiesis on efficient β-catenin degradation

Kadriye Nehir Cosgun, Huda Jumaa, Mark E. Robinson, Lars Klemm et autres

Abstract Wnt/β-catenin pathway is tightly controlled by β-catenin destruction complex to regulate lineage specification and differentiation. Compared to epithelial lineage, lymphoid cells display higher rates of β-catenin degradation to achieve constitutively low levels of β-catenin. Emphasizing the reliance of lymphoid cells on …

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β-catenin engages IKZF factors to control lymphopoiesis

Kadriye Nehir Cosgun, Huda Jumaa, Mark E. Robinson, Liang Xu et autres

Abstract β-catenin-signaling promotes proliferation and survival in epithelial, neuronal, and mesenchymal lineages, but is dispensable for B- and T-cell development. β-catenin activation is a common oncogenic driver throughout all types of cancer with the exception of B- and T-lymphoid malignancies. Unlike epithelial …

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