EntreMed’s drug shows promise in renal cancer models

The orally administered drug, MKC-1, increased survival of tumor-bearing animals in this model. An examination of tumors following five days of oral treatment revealed inhibition of the Akt-mTOR pathway, as well as decreased angiogenesis and cell proliferation within the tumors.

Activation of the oncogenic kinase Akt and the mTOR pathway are known to be adverse prognostic factors and contributors to the pathology of metastatic renal cell carcinoma (RCC), therefore inhibitors of these pathways are of significant interest for treatment of this disease. Human RCC cell lines in vitro were shown to have marked sensitivity to MKC-1.

Data from the studies with MKC-1 demonstrate broad-acting antitumor effects, showing tumor growth inhibition or regression in multiple preclinical models, including paclitaxel-resistant models. MKC-1 has been shown to inhibit mitotic spindle formation, prevent chromosome segregation in the M-phase (mitosis) of the cell cycle, and induce apoptosis.

Mark Bray, vice president, research of EntreMed, said: “Data from preclinical studies with MKC-1 continue to support its therapeutic potential in a variety of tumor types. The data are consistent with MKC-1 targeting the mTOR pathway by a mechanism that is distinct from rapamycin-like agents, such as Temosirolimus. These results, along with the recent success of agents that target the mTOR pathway, provide validation that clinical studies with MKC-1 in cancers such as renal cell are warranted.”