Tasquinimod prevents the angiogenic rebound induced by fractionated radiation resulting in an enhanced therapeutic response of prostate cancer xenografts.

Abstract

BACKGROUND:

Tasquinimod is a novel inhibitor of tumor angiogenesis which enhances therapeutic efficacy when combined with androgen ablation and/or taxane-based chemotherapies in pre-clinical prostate cancer models. It has entered registration Phase III evaluation for the treatment of castration resistant prostate cancer. Since tasquinimod suppresses the angiogenic switch induced by tumor hypoxia as prostate cancers outgrow their blood supply, this raises the issue of whether tasquinimod also suppresses the angiogenic rebound induced by fractionated radiation thereby enhancing therapeutic response to fractionated radiation.

METHODS:

Human endothelial and prostate cancer cells in culture and human prostate cancer xenografts growing in castrated male nude mice were evaluated for their response to radiation alone and in combination with tasquinimod.

RESULTS:

At clinically relevant drug levels, tasquinimod significantly (P < 0.05) enhances anti-cancer efficacy of fractionated radiation with optimal timing for initiating daily tasquinimod treatment being after completion of the fractionated radiation.

CONCLUSIONS:

Based upon cell culture studies and tumor tissue oxygenation (i.e., pO(2)), tumor vascular volume, and tumor blood vessel density measurements, the mechanism for such enhancement and optimal timing involves tasquinimod's ability to prevent the angiogenic rebound induced by fractionated radiation.

• Authors: Susan L Dalrymple, Robyn E Becker, Haoming Zhou, Theodore L DeWeese, John T Isaacs
• Journal: The Prostate (Prostate) Vol. 72 Issue 6 Pg. 638-48 (May 01 2012) ISSN: 1097-0045 [Electronic] United States
• PMID: 21837778 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc.

Chemical References

• Angiogenesis Inhibitors
• Quinolines
• Quinolones
• Radiation-Sensitizing Agents
• tasquinimod

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Combined Modality Therapy
• Humans
• Male
• Mice
• Mice, Nude
• Neovascularization, Pathologic (drug therapy, radiotherapy, therapy)
• Prostatic Neoplasms (drug therapy, radiotherapy, therapy)
• Quinolines (therapeutic use)
• Quinolones
• Radiation-Sensitizing Agents (therapeutic use)
• Transplantation, Heterologous
• Tumor Cells, Cultured