Xenograft models for preclinical drug testing: Implications for adrenocortical cancer

Adrenocortical carcinoma (ACC) is a very rare but aggressive tumor, whose biological and cellular features and processes underlying the development, progression and metastatic evolution are still obscure. Despite many attempts to use general cytostatic and cytotoxic drugs, the only available drug therapy for advanced ACC is still represented by mitotane (MTT). However, the mechanism of action of this adrenolytic derivative of the pesticide DDT has still been poorly characterized. In this context, the development of more specific drugs for ACC treatment is based on the knowledge of the molecular pathways involved in the tumor growth. Xenograft models for the screening of such drugs at preclinical levels is mandatory. In the first part of this review, we will summarize the “pro” and “con” of the different xenograft models available for anticancer drug testing in different types of tumors in general and in the last part, we will focus on the preclinical evidence obtained so far with the use of such models applied to drug screening for anticancer effects in ACC.

► Mouse xenograft: in vivo model of patient cancer biopsy implant or tumor cell line inoculation. ► Xenogafts allow studying response of patient cancer biopsy to anticancer drug in an in vivo model. ► ACC xenografts retain dysregulation of the IGF system. ► ACC xenograft to study anticancer effects of MTT, IGF-1R inhibitors and antiangiogenic drugs.