Targeting Wee1 kinase as a therapeutic approach in Hematological Malignancies

WEE1 kinase limits CDK activities to safeguard DNA replication and mitotic entry

(2020) Camilla R. Elbæk et al.   MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS

Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations

(2019) Ainhoa Madariaga et al.   Cancers

Differential activity of ATR and WEE1 inhibitors in a highly sensitive subpopulation of DLBCL linked to replication stress

(2019) Lucy A. Young et al.   CANCER RESEARCH

DNA damage response inhibitor combinations exert synergistic antitumor activity in aggressive B cell lymphomas

(2019) Valentina Restelli et al.   MOLECULAR CANCER THERAPEUTICS

Synergism Through WEE1 and CHK1 Inhibition in Acute Lymphoblastic Leukemia

(2019) Ghelli Luserna Di Rorà et al.   Cancers

A Phase I Clinical Trial of AZD1775 in Combination with Neoadjuvant Weekly Docetaxel and Cisplatin before Definitive Therapy in Head and Neck Squamous Cell Carcinoma

(2018) Eduardo Méndez et al.   CLINICAL CANCER RESEARCH

Increased activity of both CDK1 and CDK2 is necessary for the combinatorial activity of WEE1 inhibition and cytarabine

(2018) Tamara B. Garcia et al.   LEUKEMIA RESEARCH

Proteomics Profiling of CLL Versus Healthy B-cells Identifies Putative Therapeutic Targets and a Subtype-independent Signature of Spliceosome Dysregulation

(2018) Harvey E. Johnston et al.   MOLECULAR & CELLULAR PROTEOMICS

Targeting the replication stress response in cancer

(2018) Josep V. Forment et al.   PHARMACOLOGY & THERAPEUTICS

Nanomedicines for the treatment of hematological malignancies

(2018) Anil K. Deshantri et al.   JOURNAL OF CONTROLLED RELEASE

Targeting WEE1 to enhance conventional therapies for acute lymphoblastic leukemia

(2018) Andrea Ghelli Luserna Di Rorà et al.   Journal of Hematology & Oncology

Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress

(2018) Morgane Macheret et al.   NATURE

Structural Basis of Wee Kinases Functionality and Inactivation by Diverse Small Molecule Inhibitors

(2017) Jin-Yi Zhu et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Small-Molecule Inhibitor of WEE1, AZD1775, Synergizes with Olaparib by Impairing Homologous Recombination and Enhancing DNA Damage and Apoptosis in Acute Leukemia

(2017) Tamara B. Garcia et al.   MOLECULAR CANCER THERAPEUTICS

CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest

(2017) Ashleigh M. Francis et al.   MOLECULAR CANCER THERAPEUTICS

ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response

(2017) Andrew N. Blackford et al.   MOLECULAR CELL

Orthotopic patient-derived xenografts of paediatric solid tumours

(2017) Elizabeth Stewart et al.   NATURE

The impact of replication stress on replication dynamics and DNA damage in vertebrate cells

(2017) Hervé Técher et al.   NATURE REVIEWS GENETICS

Prolonged mitotic arrest induced by Wee1 inhibition sensitizes breast cancer cells to paclitaxel

(2017) Cody W. Lewis et al.   Oncotarget

A phase I pharmacological and pharmacodynamic study of MK-1775, a Wee1 tyrosine kinase inhibitor, in monotherapy and combination with gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors.

(2017) S. Leijen et al.   JOURNAL OF CLINICAL ONCOLOGY

Update on a phase I pharmacologic and pharmacodynamic study of MK-1775, a Wee1 tyrosine kinase inhibitor, in monotherapy and combination with gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors.

(2017) J. H. M. Schellens et al.   JOURNAL OF CLINICAL ONCOLOGY

The NAE inhibitor pevonedistat interacts with the HDAC inhibitor belinostat to target AML cells by disrupting the DDR

(2016) L. Zhou et al.   BLOOD

Inhibition of CHK1 and WEE1 as a new therapeutic approach in diffuse large B cell lymphomas with MYC deregulation

(2016) Valentina Restelli et al.   BRITISH JOURNAL OF HAEMATOLOGY

Proteasomal Inhibition by Ixazomib Induces CHK1 and MYC-Dependent Cell Death in T-cell and Hodgkin Lymphoma

(2016) D. Ravi et al.   CANCER RESEARCH

The DNA damage-induced cell death response: a roadmap to kill cancer cells

(2016) Sonja Matt et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Wee1 Kinase Inhibitor AZD1775 Radiosensitizes Hepatocellular Carcinoma Regardless of TP53 Mutational Status Through Induction of Replication Stress

(2016) Kyle C. Cuneo et al.   INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS

Phase II Study of WEE1 Inhibitor AZD1775 Plus Carboplatin in Patients With TP53-Mutated Ovarian Cancer Refractory or Resistant to First-Line Therapy Within 3 Months

(2016) Suzanne Leijen et al.   JOURNAL OF CLINICAL ONCOLOGY

Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma

(2016) Rebecca S. Lescarbeau et al.   MOLECULAR CANCER THERAPEUTICS

Targeting WEE1 Kinase in Cancer

(2016) Christopher J. Matheson et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Prexasertib, a Chk1/Chk2 inhibitor, increases the effectiveness of conventional therapy in B-/T- cell progenitor acute lymphoblastic leukemia

(2016) Andrea Ghelli Luserna Di Rorà et al.   Oncotarget

Synergistic anti-leukemic interactions between panobinostat and MK-1775 in acute myeloid leukemia ex vivo

(2015) Wenxiu Qi et al.   CANCER BIOLOGY & THERAPY

Inhibiting WEE1 Selectively Kills Histone H3K36me3-Deficient Cancers by dNTP Starvation

(2015) Sophia X. Pfister et al.   CANCER CELL

Synergistic antitumor interactions between MK-1775 and panobinostat in preclinical models of pancreatic cancer

(2015) Guan Wang et al.   CANCER LETTERS

Wee-1 Kinase Inhibition Sensitizes High-Risk HPV+ HNSCC to Apoptosis Accompanied by Downregulation of MCl-1 and XIAP Antiapoptotic Proteins

(2015) N. Tanaka et al.   CLINICAL CANCER RESEARCH

FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy

(2015) G. Kim et al.   CLINICAL CANCER RESEARCH

Phase I Study of Single-Agent AZD1775 (MK-1775), a Wee1 Kinase Inhibitor, in Patients With Refractory Solid Tumors

(2015) Khanh Do et al.   JOURNAL OF CLINICAL ONCOLOGY

In vitro and in vivo single-agent efficacy of checkpoint kinase inhibition in acute lymphoblastic leukemia

(2015) Ilaria Iacobucci et al.   Journal of Hematology & Oncology

Functional Genetic Screen Identifies Increased Sensitivity to WEE1 Inhibition in Cells with Defects in Fanconi Anemia and HR Pathways

(2015) M. Aarts et al.   MOLECULAR CANCER THERAPEUTICS

Distinct but Concerted Roles of ATR, DNA-PK, and Chk1 in Countering Replication Stress during S Phase

(2015) Rémi Buisson et al.   MOLECULAR CELL

Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors

(2015) Maria Teresa Esposito et al.   NATURE MEDICINE

DNA replication origin activation in space and time

(2015) Michalis Fragkos et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Characterization of a mantle cell lymphoma cell line resistant to the Chk1 inhibitor PF-00477736

(2015) Valentina Restelli et al.   Oncotarget

AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair

(2015) James B. Ford et al.   Oncotarget

Combined inhibition of Chk1 and Wee1 as a new therapeutic strategy for mantle cell lymphoma

(2015) Rosaria Chilà et al.   Oncotarget

A regimen combining the Wee1 inhibitor AZD1775 with HDAC inhibitors targets human acute myeloid leukemia cells harboring various genetic mutations

(2014) L Zhou et al.   LEUKEMIA

Identification of Wee1 as a novel therapeutic target for mutant RAS-driven acute leukemia and other malignancies

(2014) E Weisberg et al.   LEUKEMIA

Nanomedicine strategies for hematological malignancies: what is next?

(2014) Giuseppe Visani et al.   Nanomedicine

A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia

(2014) Daniel Herranz et al.   NATURE MEDICINE

Targeting the wee1 kinase for treatment of pediatric Down syndrome acute myeloid leukemia

(2014) J. Timothy Caldwell et al.   PEDIATRIC BLOOD & CANCER

Histone deacetylase inhibitor (HDACI) mechanisms of action: Emerging insights

(2014) Prithviraj Bose et al.   PHARMACOLOGY & THERAPEUTICS

Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe

(2014) M Cornago et al.   Cell Death & Disease

ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma

(2013) M. Dreyling et al.   ANNALS OF ONCOLOGY

Wee1 kinase as a target for cancer therapy

(2013) Khanh Do et al.   CELL CYCLE

Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells

(2013) Jie Zou et al.   Journal of Hematology & Oncology

Etoposide Selectively Ablates Activated T Cells To Control the Immunoregulatory Disorder Hemophagocytic Lymphohistiocytosis

(2013) T. S. Johnson et al.   JOURNAL OF IMMUNOLOGY

Deregulated expression of circadian clock and clock-controlled cell cycle genes in chronic lymphocytic leukemia

(2013) Sobia Rana et al.   MOLECULAR BIOLOGY REPORTS

Inhibition of Wee1 Sensitizes Cancer Cells to Antimetabolite Chemotherapeutics In Vitro and In Vivo, Independent of p53 Functionality

(2013) A. A. Van Linden et al.   MOLECULAR CANCER THERAPEUTICS

Preclinical Evaluation of the WEE1 Inhibitor MK-1775 as Single-Agent Anticancer Therapy

(2013) A. D. Guertin et al.   MOLECULAR CANCER THERAPEUTICS

Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia

(2013)   NEW ENGLAND JOURNAL OF MEDICINE

Wee1 Inhibition by MK-1775 Leads to Tumor Inhibition and Enhances Efficacy of Gemcitabine in Human Sarcomas

(2013) Jenny M. Kreahling et al.   PLoS One

The role of natural killer T cells in B cell malignancies

(2013) Ghasem Ghalamfarsa et al.   TUMOR BIOLOGY

DNA Damage Sensing by the ATM and ATR Kinases

(2013) A. Marechal et al.   Cold Spring Harbor Perspectives in Biology

The Elephant and the Blind Men: Making Sense of PARP Inhibitors in Homologous Recombination Deficient Tumor Cells

(2013) Silvana B. De Lorenzo et al.   Frontiers in Oncology

RNAi screening of the kinome with cytarabine in leukemias

(2012) R. Tibes et al.   BLOOD

Combination Therapy Targeting the Chk1 and Wee1 Kinases Shows Therapeutic Efficacy in Neuroblastoma

(2012) M. R. Russell et al.   CANCER RESEARCH

Cyclin F-Mediated Degradation of Ribonucleotide Reductase M2 Controls Genome Integrity and DNA Repair

(2012) Vincenzo D'Angiolella et al.   CELL

Antitumor activity of new pyrazolo[3,4-d]pyrimidine SRC kinase inhibitors in Burkitt lymphoma cell lines and its enhancement by WEE1 inhibition

(2012) Martina Cozzi et al.   CELL CYCLE

Combined inhibition of Chk1 and Wee1: In vitro synergistic effect translates to tumor growth inhibition in vivo

(2012) Laura Carrassa et al.   CELL CYCLE

Doxorubicin induces the DNA damage response in cultured human mesenchymal stem cells

(2012) Séverine Cruet-Hennequart et al.   INTERNATIONAL JOURNAL OF HEMATOLOGY

Integrated genomic analyses identify WEE1 as a critical mediator of cell fate and a novel therapeutic target in acute myeloid leukemia

(2012) C C Porter et al.   LEUKEMIA

Cyclin-Dependent Kinase Suppression by WEE1 Kinase Protects the Genome through Control of Replication Initiation and Nucleotide Consumption

(2012) H. Beck et al.   MOLECULAR AND CELLULAR BIOLOGY

Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer

(2012) Jonathan Ledermann et al.   NEW ENGLAND JOURNAL OF MEDICINE

Forced activation of Cdk1 via wee1 inhibition impairs homologous recombination

(2012) M Krajewska et al.   ONCOGENE

High Expression of Wee1 Is Associated with Poor Disease-Free Survival in Malignant Melanoma: Potential for Targeted Therapy

(2012) Gry Irene Magnussen et al.   PLoS One

Forced Mitotic Entry of S-Phase Cells as a Therapeutic Strategy Induced by Inhibition of WEE1

(2012) Marieke Aarts et al.   Cancer Discovery

Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow-derived mesenchymal stromal cells

(2011) A. H. Nwabo Kamdje et al.   BLOOD

Chk1 inhibition and Wee1 inhibition combine synergistically to impede cellular proliferation

(2011) Kurtis D. Davies et al.   CANCER BIOLOGY & THERAPY

Therapeutic Implications for the Induced Levels of Chk1 in Myc-Expressing Cancer Cells

(2011) A. Hoglund et al.   CLINICAL CANCER RESEARCH

MK-1775, a Potent Wee1 Inhibitor, Synergizes with Gemcitabine to Achieve Tumor Regressions, Selectively in p53-Deficient Pancreatic Cancer Xenografts

(2011) N. V. Rajeshkumar et al.   CLINICAL CANCER RESEARCH

WEE1 Kinase Targeting Combined with DNA-Damaging Cancer Therapy Catalyzes Mitotic Catastrophe

(2011) P. C. De Witt Hamer et al.   CLINICAL CANCER RESEARCH

Targeting the S and G2 checkpoint to treat cancer

(2011) Tao Chen et al.   DRUG DISCOVERY TODAY

Flt3-ITD alters chemotherapy response in vitro and in vivo in a p53-dependent manner

(2011) Timothy S. Pardee et al.   EXPERIMENTAL HEMATOLOGY

Wee1 controls genomic stability during replication by regulating the Mus81-Eme1 endonuclease

(2011) Raquel Domínguez-Kelly et al.   JOURNAL OF CELL BIOLOGY

MK1775, a Selective Wee1 Inhibitor, Shows Single-Agent Antitumor Activity against Sarcoma Cells

(2011) J. M. Kreahling et al.   MOLECULAR CANCER THERAPEUTICS

Targeting ATR and Chk1 kinases for cancer treatment: A new model for new (and old) drugs

(2011) Luis I. Toledo et al.   Molecular Oncology

Navigating the kinome

(2011) James T Metz et al.   Nature Chemical Biology

Mitotic catastrophe: a mechanism for avoiding genomic instability

(2011) Ilio Vitale et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Safeguarding genome integrity: the checkpoint kinases ATR, CHK1 and WEE1 restrain CDK activity during normal DNA replication

(2011) C. S. Sorensen et al.   NUCLEIC ACIDS RESEARCH

New pyrazolo[3,4-d]pyrimidine SRC inhibitors induce apoptosis in mesothelioma cell lines through p27 nuclear stabilization

(2011) P Indovina et al.   ONCOGENE

Targeting the checkpoint kinase WEE1: Selective sensitization of cancer cells to DNA-damaging drugs

(2010) Paola Indovina et al.   CANCER BIOLOGY & THERAPY

MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil

(2010) Hiroshi Hirai et al.   CANCER BIOLOGY & THERAPY

In Silico Analysis of Kinase Expression Identifies WEE1 as a Gatekeeper against Mitotic Catastrophe in Glioblastoma

(2010) Shahryar E. Mir et al.   CANCER CELL

New Insights into Checkpoint Kinase 1 in the DNA Damage Response Signaling Network

(2010) Y. Dai et al.   CLINICAL CANCER RESEARCH

New pyrazolo-[3,4-d]-pyrimidine derivative Src kinase inhibitors lead to cell cycle arrest and tumor growth reduction of human medulloblastoma cells

(2010) Alessandra Rossi et al.   FASEB JOURNAL

Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase

(2010) Halfdan Beck et al.   JOURNAL OF CELL BIOLOGY

Poly(ADP)-Ribose Polymerase Inhibition: Frequent Durable Responses inBRCACarrier Ovarian Cancer Correlating With Platinum-Free Interval

(2010) Peter C. Fong et al.   JOURNAL OF CLINICAL ONCOLOGY

Rearrangement ofMYCIs Associated With Poor Prognosis in Patients With Diffuse Large B-Cell Lymphoma Treated in the Era of Rituximab

(2010) Sharon Barrans et al.   JOURNAL OF CLINICAL ONCOLOGY

Anomalous constitutive Src kinase activity promotes B lymphoma survival and growth

(2010) Jiyuan Ke et al.   Molecular Cancer

The DNA Damage Response: Making It Safe to Play with Knives

(2010) Alberto Ciccia et al.   MOLECULAR CELL

How I treat mantle cell lymphoma

(2009) M. Ghielmini et al.   BLOOD

Constitutive Activation of the DNA Damage Signaling Pathway in Acute Myeloid Leukemia with Complex Karyotype: Potential Importance for Checkpoint Targeting Therapy

(2009) C. Cavelier et al.   CANCER RESEARCH

Tyrosines in the Kinesin-5 Head Domain Are Necessary for Phosphorylation by Wee1 and for Mitotic Spindle Integrity

(2009) Kristin Garcia et al.   CURRENT BIOLOGY

PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination

(2009) Helen E Bryant et al.   EMBO JOURNAL

Inappropriate Activation of Cyclin-dependent Kinases by the Phosphatase Cdc25b Results in Premature Mitotic Entry and Triggers a p53-dependent Checkpoint

(2009) Shohreh Varmeh et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Attempts to Optimize Induction and Consolidation Treatment in Acute Myeloid Leukemia: Results of the MRC AML12 Trial

(2009) Alan K. Burnett et al.   JOURNAL OF CLINICAL ONCOLOGY

Therapeutic implications of Src independent calcium mobilization in diffuse large B-cell lymphoma

(2009) C. Annette Hollmann et al.   LEUKEMIA RESEARCH

CHK1 inhibition as a strategy for targeting fanconi anemia (FA) DNA repair pathway deficient tumors

(2009) Clark C Chen et al.   Molecular Cancer

Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents

(2009) H. Hirai et al.   MOLECULAR CANCER THERAPEUTICS

Cdk1 Participates in BRCA1-Dependent S Phase Checkpoint Control in Response to DNA Damage

(2009) Neil Johnson et al.   MOLECULAR CELL

Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions

(2009) Peter J. Cook et al.   NATURE

Integrated Functional, Gene Expression and Genomic Analysis for the Identification of Cancer Targets

(2009) Elizabeth Iorns et al.   PLoS One

G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer

(2008) N Bucher et al.   BRITISH JOURNAL OF CANCER

Antiproliferative and proapoptotic activities of new pyrazolo[3,4-d]pyrimidine derivative Src kinase inhibitors in human osteosarcoma cells

(2008) Adriano Spreafico et al.   FASEB JOURNAL

Tyrosine kinase inhibition in diffuse large B-cell lymphoma: molecular basis for antitumor activity and drug resistance of dasatinib

(2008) C Yang et al.   LEUKEMIA

Nucleoside analogs: molecular mechanisms signaling cell death

(2008) B Ewald et al.   ONCOGENE