HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Bone-specific growth inhibition of prostate cancer metastasis by atrasentan.

Abstract
Advanced prostate cancer frequently metastasizes to bone and remains an incurable disease. One recent experimental therapy involves endothelin receptor A (ETA) antagonists (e.g., atrasentan). Clinical results to date have been mixed, with atrasentan not meeting its primary endpoints in a Phase III trial. It remains an open question whether some patients might benefit from this therapy, while others may not. Preclinical data supports the concept that the endothelin signaling axis may be particularly important for tumor growth in bone, but the extent to which it is involved in metastatic colonization of other organ sites in prostate cancer remains unclear. Here we evaluate the efficacy of atrasentan in a mouse model of prostate cancer metastatic colonization. Using bioluminescence imaging, we show that atrasentan does inhibit tumor growth in, but not the initial colonization of, bony sites in intracardially-injected 22Rv1 prostate cancer cells. However, atrasentan shows little efficacy in soft tissues such as adrenal gland or liver. Our studies show that whether atrasentan exhibits significant overall antitumor efficacy and survival benefit depends on the presence of bone metastasis evident in that animal. Though in contrast to previous findings efficacy is apparent in a prostate tumor model that elicits mixed osteoblastic/osteolytic lesions. These data confirm the notion that atrasentan may exhibit selective activity against prostate cancer bone metastasis, mirroring clinical findings, and suggest that the role of endothelin signaling in bone metastasis may be more complex than previously appreciated. The model described here may provide a valuable tool for unraveling this complexity.
AuthorsJustin M Drake, Joshua R Danke, Michael D Henry
JournalCancer biology & therapy (Cancer Biol Ther) Vol. 9 Issue 8 Pg. 607-14 (Apr 15 2010) ISSN: 1555-8576 [Electronic] United States
PMID20139704 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Pyrrolidines
  • atrasentan
Topics
  • Adenocarcinoma (drug therapy, pathology, secondary)
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Bone Neoplasms (drug therapy, secondary)
  • Cell Growth Processes (drug effects)
  • Cell Line, Tumor
  • Humans
  • Male
  • Mice
  • Prostatic Neoplasms (drug therapy, pathology)
  • Pyrrolidines (pharmacology)
  • Random Allocation
  • Xenograft Model Antitumor Assays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: