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Oliver Hantschel

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Related publications (41)

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Btk SH2-kinase interface is critical for allosteric kinase activation and its targeting inhibits B-cell neoplasms

Matteo Dal Peraro, Oliver Hantschel, Florence Pojer, Sandrine Madeleine Suzanne Georgeon, Maria Josefina Marcaida Lopez, Allan Joaquim Lamontanara, Grégory La Sala, Tim Kükenshöner, Daniel Pereira Duarte

Bruton's tyrosine kinase (Btk) is critical for B-cell maturation and activation. Btk loss-of-function mutations cause human X-linked agammaglobulinemia (XLA). In contrast, Btk signaling sustains growth of several B-cell neoplasms which may be treated with ...

Nature Publishing Group2020

γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia

Anja Irmisch, Oliver Hantschel, Jörg Hülsken

The BCR-ABL1 fusion protein is the cause of chronic myeloid leukemia (CML) and of a significant fraction of adult-onset B cell acute lymphoblastic leukemia (B-ALL) cases. Using mouse models and patient-derived samples, we identified an essential role for γ ...

2019

Allosteric kinase inhibitors

Oliver Hantschel

Background. Inhibition of the kinase activity of the BCR-ABL1 oncoprotein by an allosteric mechanism of action facilitates alternative treatment options for chronic myeloid leukemia (CML) patients who cannot be adequately treated with conventional catalyti ...

Springer Nature2017

Targeting BCR-ABL and JAK2 in Ph+ ALL

Oliver Hantschel

In this issue of Blood, Appelmann et al provide evidence for prolonged survival and prevention of resistance in a mouse model of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) by combined targeting of the BCR-ABL kinase and Janus ...

2015

Normal ABL1 is a tumor suppressor and therapeutic target in human and mouse leukemias expressing oncogenic ABL1 kinases

Oliver Hantschel

Leukemias expressing constitutively activated mutants of ABL1 tyrosine kinase (BCR-ABL1, TEL-ABL1, NUP214-ABL1) usually contain at least 1 normal ABL1 allele. Because oncogenic and normal ABL1 kinases may exert opposite effects on cell behavior, we examine ...

American Society of Hematology2016

Unexpected Off-Targets and Paradoxical Pathway Activation by Kinase Inhibitors

Oliver Hantschel

Protein kinase inhibitors are an increasingly important class of targeted anticancer therapeutics. More than two dozen new drugs of this class have entered routine clinical use over the past decade. This review article focuses on how the development of met ...

2015

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Allan Joaquim Lamontanara

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both confo ...

Nature Research2014

Structure, regulation, signaling, and targeting of abl kinases in cancer

Oliver Hantschel

Abl kinases are prototypic cytoplasmic tyrosine kinases and are involved in a variety of chromosomal aberrations in different cancers. This causes the expression of Abl fusion proteins, such as Bcr-Abl, that are constitutively activated and drivers of tumo ...

2012

Kinase-templated abiotic reaction

Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon

Protein kinases are quintessential regulators of cellular function. Numerous pathologies are intimately linked to the dysregulated activity of a particular protein kinase. Herein we report a technology based on a proximity-induced chemical transformation t ...

2017

Kinase Regulation in Mycobacterium tuberculosis: Variations on a Theme

Oliver Hantschel, Sina Maren Reckel

In this issue of Structure, Lisa et al. (2015) examine how the PknG protein kinase of M. tuberculosis efficiently binds and phosphorylates substrates. The work highlights interesting parallels between PknG and eukaryotic protein kinases. ...

Elsevier2015

Cell biology: a key driver of therapeutic innovation

Oliver Hantschel

All processes associated with cellular function are likely to contribute to disease. Particularly in the cancer field, most major therapeutic innovations have originated from the elucidation of basic molecular mechanisms by academic researchers. Recent bre ...

Rockefeller University Press2012

Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase

Oliver Hantschel, Florence Pojer, Sandrine Madeleine Suzanne Georgeon, Sina Maren Reckel, Charlotte Julie Caroline Gehin, Tim Kükenshöner, Delphine Maude Tardivon, Barbara Gerig

The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study ...

Springer Nature2017

Mechanisms of resistance to BCR-ABL and other kinase inhibitors

Orest Kuzyk, Oliver Hantschel, Allan Joaquim Lamontanara, Emel Basak Gencer Akçok

In this article, we are reviewing the molecular mechanisms that lead to kinase inhibitor resistance. As the oncogenic BCR-ABL kinase is the target of the first approved small-molecule kinase inhibitor imatinib, we will first focus on the structural and mec ...

Elsevier Science Bv2013

Development of Mirror-Image Monobodies for Targeted Cancer Therapies

Oliver Hantschel, Tim Kükenshöner, Timothy Matthias Reichart

WILEY2018

The phosphatase UBASH3B/Sts-1 is a negative regulator of Bcr-Abl kinase activity and leukemogenesis

Oliver Hantschel

2019

Specificity and mechanism-of-action of the JAK2 tyrosine kinase inhibitors ruxolitinib and SAR302503 (TG101348)

Oliver Hantschel, Roland Moser, Sandrine Madeleine Suzanne Georgeon

Nature Publishing Group2014

Modulating protein-protein interaction with a molecular tether

Kai Johnsson, Oliver Hantschel, Helen Rebecca Ostlund Farrants

Wiley-Blackwell2015

Nilotinib as frontline and second-line therapy in chronic myeloid leukemia: open questions

Oliver Hantschel

Nilotinib is a second generation ABL tyrosine kinase inhibitor (TKI) that exerts major anti-leukemic effects in newly diagnosed patients with chronic myeloid leukemia (CML) as well as in most patients with imatinib-resistant CML. In freshly diagnosed patie ...

2012

BCR-ABL1 compound mutants display differential and dose-dependent responses to ponatinib

Oliver Hantschel

2018

2016 International Symposium on Chemical Biology of the NCCR Chemical Biology Campus Biotech, Geneva 13-15.1.2016

Beat Fierz, Oliver Hantschel

Schweizerische Chemische Gesellschaft2016