In vivo models for endocrine-dependent breast carcinomas: special considerations of clinical relevance.
Tumours in hormone-regulated organs such as the breast, prostate or ovaries are among the most frequent malignancies. Because of their endocrine-dependent development and growth, they offer a unique opportunity for antihormonal treatment either single or long-term or in combination with radio- or chemotherapy. A prominent example is breast carcinoma, for which the anti-oestrogen tamoxifen has been used successfully for several years. Unfortunately, a substantial number of tumours are intrinsically tamoxifen-resistant, despite oestrogen-receptor positivity, and, eventually, almost all breast carcinomas acquire resistance towards tamoxifen. The recently developed pure anti-oestrogen Faslodex and the third-generation aromatase inhibitors (Letrozol, anastrozole (Arimidex) offer the possibility of alternative therapies. Preclinical models are needed, as most of the mechanisms of hormonal tumour dependence and the causes of the appearance of antihormone resistance are not yet fully understood. This review focuses on the development and characterisation of breast cancer xenografts derived directly from surgical resections. With their help, a deeper insight into the mechanisms of hormone regulation and anti-oestrogen resistance can be gained. The xenograft models have already been used in differential gene-expression analysis on DNA microarrays and for the evaluation of approaches to overcoming tamoxifen resistance.
Fichtner
I
I
Max-Delbrück-Center for Molecular Medicine, Experimental Pharmacology, Robert-Roessle-Str. 10, D-13092 Berlin, Germany. fichtner@mdc-berlin.de
Becker
M
M
Zeisig
R
R
Sommer
A
A
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D006801:Humans; D008954:Models, Biological; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D013629:Tamoxifen