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Πέμπτη 4 Ιουλίου 2019

Poly (ADP) ribose glycohydrolase can be effectively targeted in pancreatic cancer
Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have an average survival of less than one year, underscoring the importance of evaluating novel targets with matched targeted agents. We recently identified that poly (ADP) ribose glycohydrolase (PARG) is a strong candidate target due to its dependence on the pro-oncogenic mRNA stability factor HuR (ELAVL1). Here, we evaluated PARG as a target in PDAC models using both genetic silencing of PARG and established small molecule PARG inhibitors,...
Cancer Research Online First Articles
Thu Jul 04, 2019 16:24
CXCR7 reactivates ERK signaling to promote resistance to EGFR kinase inhibitors in NSCLC.
Although EGFR mutant-selective TKIs are clinically effective, acquired resistance can occur by reactivating ERK. We show using in vitro models of acquired EGFR TKI resistance with a mesenchymal phenotype that CXCR7, an atypical GPCR, activates the MAPK-ERK pathway via β-arrestin. Depletion of CXCR7 inhibited the MAPK pathway, significantly attenuated EGFR TKI resistance and resulted in mesenchymal to epithelial transition. CXCR7 overexpression was essential in reactivation of ERK1/2 for the generation...
Cancer Research Online First Articles
Thu Jul 04, 2019 16:24
Deletion of the Miz-1 POZ domain increases efficacy of cytarabine treatment in T- and B-ALL/lymphoma mouse models
Acute lymphoblastic leukemia (ALL) is an aggressive blood cancer that mainly affects children. Relapse rates are high and toxic chemotherapies that block DNA replication and induce DNA damage lead to health problems later in life, underlining the need for improved therapies. c-Myc is a transcription factor that is hyperactive in a large proportion of cancers including leukemia but is difficult to target in therapy. We show that ablation of the function of the BTB/POZ domain factor Miz-1, an important...
Cancer Research Online First Articles
Thu Jul 04, 2019 16:24
Temozolomide sensitizes MGMT-deficient tumor cells to ATR inhibitors
O6-methylguanine-DNA methyltransferase (MGMT) is an enzyme that removes alkyl groups at the O6-position of guanine in DNA. MGMT expression is reduced or absent in many tumor types derived from a diverse range of tissues, most notably in glioma. Low MGMT expression confers significant sensitivity to DNA alkylating agents such as temozolomide (TMZ), providing a natural therapeutic index over normal tissue. In this study, we sought to identify novel approaches which could maximally exploit the therapeutic...
Cancer Research Online First Articles

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