In the dose expansion (n = 68), patients with MDM2-amplified (well-differentiated and de-differentiated liposarcomas [WDLPS and DDLPS], glioblastoma multiforme [GBM], or other solid tumors [OST]), MDM2-overexpressing ER+ breast cancer (BC), or MM received AMG 232 at the maximum tolerated dose (MTD).
Effects of posaconazole (a strong CYP3A4 inhibitor), two new tablet formulations, and food on the pharmacokinetics of idasanutlin, an MDM2 antagonist, in patients with advanced solid tumors.
It binds to and inhibits key proteins like p53 and the RB protein, and MDM2 amplification as well as protein overexpression without amplification is seen in many solid tumors.
A single nucleotide polymorphism (SNP) at position 309 in the promoter region of MDM2 leading to increased expression of MDM2 and attenuated function of p53 has been negatively associated with onset and outcome of disease in solid tumors.
The human homologue of the mouse double minute 2 (MDM2) oncogene is overexpressed in more than forty different types of malignancies, including solid tumors, sarcomas and leukemias.
Therefore, breast tumors differ from other solid tumors reported previously in that no internal deletions of MDM2 protein coding sequences were observed.