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Synergistic Activity of PARP Inhibition by Talazoparib (BMN 673) with Temozolomide in Pediatric Cancer Models in the Pediatric Preclinical Testing Program
Purpose: Inhibitors of PARP, an enzyme involved in base excision repair, have demonstrated single-agent activity against tumors deficient in homologous repair processes. Ewing sarcoma cells are also… Expand
IGF-I mediated survival pathways in normal and malignant cells.
The type-I and -II insulin-like growth factors (IGF-I, II) are now established as survival- or proliferation-factors in many in vitro systems. Of note IGFs provide trophic support for multiple cell… Expand
Initial testing (stage 1) of the polo‐like kinase inhibitor volasertib (BI 6727), by the Pediatric Preclinical Testing Program
Volasertib (BI 6727) is a potent inhibitor of Polo‐like kinase 1 (Plk1), that is overexpressed in several childhood cancers and cell lines. Because of its novel mechanism of action, volasertib was… Expand
Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia.
The clinical success of the BCL-2-selective BH3-mimetic venetoclax in patients with poor prognosis chronic lymphocytic leukemia (CLL) highlights the potential of targeting the BCL-2-regulated… Expand
Initial testing (stage 1) of the histone deacetylase inhibitor, quisinostat (JNJ‐26481585), by the Pediatric Preclinical Testing Program
Quisinostat (JNJ‐26481585) is a second‐generation pyrimidyl‐hydroxamic acid histone deacetylase (HDAC) inhibitor with high cellular potency towards Class I and II HDACs. Quisinostat was selected for… Expand
The insulin-like growth factor-1 receptor-targeting antibody, CP-751,871, suppresses tumor-derived VEGF and synergizes with rapamycin in models of childhood sarcoma.
- R. Kurmasheva, L. Dudkin, C. Billups, L. Debelenko, C. Morton, P. Houghton
- Biology, Medicine
- Cancer research
- 1 October 2009
Signaling through the type 1 insulin-like growth factor receptor (IGF-1R) occurs in many human cancers, including childhood sarcomas. As a consequence, targeting the IGF-1R has become a focus for… Expand
IRS-1: auditing the effectiveness of mTOR inhibitors.
Rapamycin analogs that inhibit mTOR signaling have antitumor activity against certain lymphomas, but treatment of solid tumors has been less encouraging despite inhibition of mTOR function. Two… Expand
Potent Inhibition of Angiogenesis by the IGF-1 Receptor-Targeting Antibody SCH717454 Is Reversed by IGF-2
- H. Bid, Jun Zhan, D. Phelps, R. Kurmasheva, P. Houghton
- Biology, Medicine
- Molecular Cancer Therapeutics
- 21 December 2011
Previously, we reported that a predominant action of a type-1 insulin-like growth factor receptor (IGF-1R)-targeted antibody was through inhibiting tumor-derived VEGF, and indirectly, angiogenesis.… Expand
Effective Targeting of the P53–MDM2 Axis in Preclinical Models of Infant MLL-Rearranged Acute Lymphoblastic Leukemia
Purpose: Although the overall cure rate for pediatric acute lymphoblastic leukemia (ALL) approaches 90%, infants with ALL harboring translocations in the mixed-lineage leukemia (MLL) oncogene (infant… Expand
Predicted mechanisms of resistance to mTOR inhibitors
The serine/threonine kinase, mTOR (mammalian Target of Rapamycin) has become a focus for cancer drug development. Rapamycins are highly specific inhibitors of mTOR and potently suppress tumour cell… Expand