EntreMed's Panzem shows action against brain cancer

New York, April 3 - EntreMed, Inc. said preclinical research for its lead clinical-stage compound Panzem (2-methoxyestradiol or 2ME2) found it can be combined with the maximally tolerated doses of standard chemotherapeutic agents without adding to toxicity and that it shows action against brain cancer.

In one preclinical study, daily oral administration of 2ME2 in combination with a maximally tolerated course of Temodar (temozolomide) resulted in 87% growth inhibition of advanced glioblastoma (brain cancer). Treatment with either 2ME2 or Temodar alone was only marginally effective in slowing tumor growth, EntreMed said.

In a separate preclinical study, 2ME2 was used in combination with a maximally tolerated course of 5-fluorouracil (5FU) in colon carcinoma. Daily oral administration of 2ME2 with 5FU resulted in 84% growth inhibition of established tumors, while treatment with either agent alone was only minimally effective in arresting tumor growth.

EntreMed added that the preclinical results suggest that incorporating 2ME2 into maximally tolerated courses of temozolomide or 5FU for cancer treatment may provide the ability to maximize the therapeutic potential of each agent. In addition, reduced doses of temozolomide or 5FU are not required when combined with 2ME2.

The findings were presented at the 97th Annual Meeting of the American Association for Cancer Research in Washington, D.C.

EntreMed, a Rockville, Md., pharmaceutical company, also presented preclinical results for ENMD-1198, a novel tubulin binding agent.

Oral administration of ENMD-1198 showed pronounced in vivo antitumor activity in three preclinical models of human cancer, the company reported.

Daily oral treatment with ENMD-1198 in an orthotopic MDA MB 231 breast cancer model led to the disruption of microtubules within tumor cells and a substantial decrease in HIF-1alpha, a tumor cell survival protein over-expressed in more than 70% of human tumors. HIF-1alpha over-expression correlates with tumor aggressiveness, metastases and poor prognosis.

Activation of two additional transcription factors, NFkappaB and Stat3, known to modulate HIF-1alpha protein levels in vitro and promote tumorigenesis, were also reduced following daily oral ENMD-1198 treatment. All three transcription factors are known to regulate multiple genes and their proteins that contribute to tumor growth, angiogenesis and progression.

In a separate preclinical orthotopic breast cancer model, serum proteins regulated by HIF-1alpha, NFkappaB and Stat3, were also reduced substantially following oral administration of ENMD-1198.

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