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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody

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Anti-endothelin drugs in solid tumors.

Antonio Russo¹, Giuseppe Bronte, Sergio Rizzo

¹Università di Palermo, Section of Medical Oncology, Department of Surgical and Oncological Sciences, Via del Vespro 129, 90127 Palermo, Italy. lab-oncobiologia@usa.net

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|January 28, 2010

Summary

Endothelin receptor blockade, including with atrasentan, shows promise for castration-resistant prostate cancer (CRPC). While active, further evidence is needed to confirm its efficacy in improving survival for CRPC patients.

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Area of Science:

Oncology
Pharmacology
Molecular Biology

Background:

The endothelin (ET) axis regulates normal tissue functions and is implicated in tumor growth and progression.
ET-1 receptor blockade is a potential therapeutic strategy for various cancers.
The ET axis plays a role in cancer development mechanisms.

Purpose of the Study:

To provide a comprehensive view of atrasentan for castration-resistant prostate cancer (CRPC) treatment.
To present the scientific rationale for ET receptor blockade in cancer.
To review clinical trials of ET antagonists.

Main Methods:

Literature research using PubMed and Pharmaprojects.
Review of clinical investigations of atrasentan in prostate cancer.
Analysis of ET antagonist clinical trials.

Main Results:

Atrasentan demonstrates antitumor activity, bone metastasis control, and pain amelioration in CRPC.
Improvement in time to progression and overall survival with atrasentan is yet to be demonstrated.
Clinical findings regarding zibotentan are also noted.

Conclusions:

Atrasentan appears active in CRPC, but robust scientific evidence is still required.
The ET axis is a relevant target for CRPC therapy.
Further research is warranted to establish the role of ET antagonists in CRPC.