1. Academic Validation
  2. Lack of long-lasting effects of mitotane adjuvant therapy in a mouse xenograft model of adrenocortical carcinoma

Lack of long-lasting effects of mitotane adjuvant therapy in a mouse xenograft model of adrenocortical carcinoma

  • Mol Cell Endocrinol. 2013 Dec 5;381(1-2):66-9. doi: 10.1016/j.mce.2013.07.023.
Mabrouka Doghman 1 Enzo Lalli
Affiliations

Affiliation

  • 1 Institut de Pharmacologie Moléculaire et Cellulaire CNRS, Valbonne, France; Associated International Laboratory (LIA) NEOGENEX CNRS, Valbonne, France; University of Nice-Sophia-Antipolis, Valbonne, France.
Abstract

Mitotane is a widely used drug in the therapy of adrenocortical carcinoma (ACC). It is important to set up preclinical protocols to study the possible synergistic effects of its association with new drugs for ACC therapy. We assessed the efficacy of different routes of administration of mitotane (i.p. and oral) in inhibiting growth of H295R ACC cell xenografts in an Adjuvant setting. Both formulations of mitotane could inhibit H295R xenografts growth only at short times after carcinoma cells inoculation, even though plasma mitotane levels approached or fell within the therapeutic range in humans. Our results show that mitotane Adjuvant therapy is inadequate to antagonize long-term growth of H295R Cancer cells xenografts and that care should then be taken in the design of preclinical protocols to evaluate the performance of new drugs in association with mitotane.

Keywords

ACC; Adrenal cortex; Cancer; Mitotane; NOD/SCID; Xenografts; adrenocortical carcinoma; non-obese diabetic/severe combined immunodeficiency.

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