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DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.
(MASSACHUSETTS MEDICAL SOC, 2015-10-29)
BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would ...
Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer.
(MASSACHUSETTS MEDICAL SOC, 2020-12-10)
BACKGROUND: We previously reported that olaparib led to significantly longer imaging-based progression-free survival than the physician's choice of enzalutamide or abiraterone among men with metastatic castration-resistant ...
Protein-altering germline mutations implicate novel genes related to lung cancer development.
(NATURE PORTFOLIO, 2020-05-11)
Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect ...
ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment.
(AMER ASSOC CANCER RESEARCH, 2019-06-01)
PURPOSE: ATR inhibitors (ATRi) are in early phase clinical trials and have been shown to sensitize to chemotherapy and radiotherapy preclinically. Limited data have been published about the effect of these drugs on the ...
PARP Inhibitors for Advanced Prostate Cancer: Validating Predictive Biomarkers.
(ELSEVIER, 2019-10-01)
Olaparib for Metastatic Castration-Resistant Prostate Cancer.
(MASSACHUSETTS MEDICAL SOC, 2020-05-28)
BACKGROUND: Multiple loss-of-function alterations in genes that are involved in DNA repair, including homologous recombination repair, are associated with response to poly(adenosine diphosphate-ribose) polymerase (PARP) ...
Overexpression of Claspin and Timeless protects cancer cells from replication stress in a checkpoint-independent manner.
(NATURE PUBLISHING GROUP, 2019-02-22)
Oncogene-induced replication stress (RS) promotes cancer development but also impedes tumor growth by activating anti-cancer barriers. To determine how cancer cells adapt to RS, we have monitored the expression of different ...
Sp1 phosphorylation by ATM downregulates BER and promotes cell elimination in response to persistent DNA damage.
(OXFORD UNIV PRESS, 2018-02-28)
ATM (ataxia-telangiectasia mutated) is a central molecule for DNA quality control. Its activation by DNA damage promotes cell-cycle delay, which facilitates DNA repair prior to replication. On the other hand, persistent ...
Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2.
(CELL PRESS, 2016-08-08)
Mutations in the isocitrate dehydrogenase-1 gene (IDH1) are common drivers of acute myeloid leukemia (AML) but their mechanism is not fully understood. It is thought that IDH1 mutants act by inhibiting TET2 to alter DNA ...
Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint.
(ELIFE SCIENCES PUBLICATIONS LTD, 2019-05-28)
Coordination of the cellular response to DNA damage is organised by multi-domain 'scaffold' proteins, including 53BP1 and TOPBP1, which recognise post-translational modifications such as phosphorylation, methylation and ...