Cancer Therapy: Preclinical BET Bromodomain Inhibition of MYC-Amplified Medulloblastoma
نویسندگان
چکیده
Purpose: MYC-amplified medulloblastomas are highly lethal tumors. Bromodomain and extraterminal (BET) bromodomain inhibition has recently been shown to suppress MYC-associated transcriptional activity in other cancers. The compound JQ1 inhibits BET bromodomain-containing proteins, including BRD4. Here, we investigate BET bromodomain targeting for the treatment of MYC-amplified
منابع مشابه
BET bromodomain inhibition of MYC-amplified medulloblastoma.
PURPOSE MYC-amplified medulloblastomas are highly lethal tumors. Bromodomain and extraterminal (BET) bromodomain inhibition has recently been shown to suppress MYC-associated transcriptional activity in other cancers. The compound JQ1 inhibits BET bromodomain-containing proteins, including BRD4. Here, we investigate BET bromodomain targeting for the treatment of MYC-amplified medulloblastoma. ...
متن کاملBET bromodomain protein inhibition is a therapeutic option for medulloblastoma
Medulloblastoma is the most common malignant brain tumor of childhood, and represents a significant clinical challenge in pediatric oncology, since overall survival currently remains under 70%. Patients with tumors overexpressing MYC or harboring a MYC oncogene amplification have an extremely poor prognosis. Pharmacologically inhibiting MYC expression may, thus, have clinical utility given its ...
متن کاملInhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma
Medulloblastoma is a pediatric brain tumor with a variable prognosis due to clinical and genomic heterogeneity. Among the 4 major genomic sub-groups, patients with MYC amplified tumors have a particularly poor prognosis despite therapy with surgery, radiation and chemotherapy. Targeting the MYC oncogene has traditionally been problematic. Here we report that MYC driven medulloblastoma can be ta...
متن کاملCancer Therapy: Preclinical Inhibition of Bromodomain Proteins for the Treatment of Human Diffuse Large B-cell Lymphoma
Purpose: Approximately 50% of patients with diffuse large Bcell lymphoma (DLBCL) enter long-term remission after standard chemotherapy. Patients with DLBCL who do not respond to chemotherapy have few treatment options. There remains a critical need to identify effective and targeted therapeutics for DLBCL. Experimental Design: Recent studies have highlighted the incidence of increased c-MYC pro...
متن کاملCancer Therapy: Preclinical Efficacy of BET Bromodomain Inhibition in Kras-Mutant Non–Small Cell Lung Cancer
Purpose: Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency ofmutantKras tumors onMYC function.Unfortunately, drug-like small-molecule inhibitors ...
متن کامل