Skip Navigation LinksHome > July 2014 - Volume 26 - Issue 4 > The DREAM complex in antitumor activity of imatinib mesylate...
Current Opinion in Oncology:
doi: 10.1097/CCO.0000000000000090
SARCOMAS: Edited by Jonathan C. Trent

The DREAM complex in antitumor activity of imatinib mesylate in gastrointestinal stromal tumors

DeCaprio, James A.a,b; Duensing, Anettec,d

Collapse Box


Purpose of review: Although most gastrointestinal stromal tumors respond well to treatment with the small molecule kinase inhibitor imatinib mesylate (Gleevec), complete remissions are rare and the majority of patients achieve disease stabilization. Furthermore, discontinuation of treatment in the presence of residual tumor mass almost inevitably leads to tumor progression. These observations suggest that a subset of tumor cells not only persists under imatinib treatment, but remains viable. The current article reviews the molecular basis for these findings and explores strategies to exploit them therapeutically.

Recent findings: Although imatinib induces apoptosis in a subset of gastrointestinal stromal tumor cells, it leads to a reversible exit from the cell division cycle and entry into G0, a cell cycle state called quiescence, in the remaining cells. Mechanistically, this process involves the DREAM complex (DP, p130/RBL2, E2F4 and MuvB), a newly identified key regulator of quiescence. Interfering with DREAM complex formation either by siRNA-mediated knockdown or by pharmacological inhibition of the regulatory kinase dual-specificity tyrosine phosphorylation-regulated kinase 1A was shown to enhance imatinib-induced gastrointestinal stromal tumor cell death.

Summary: Targeting the DREAM complex and imatinib-induced quiescence could provide opportunities for future therapeutic interventions toward more efficient imatinib responses.

© 2014 Lippincott Williams & Wilkins, Inc.


Article Tools


Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.