Growth of LAPC4 prostate cancer xenograft tumor is insensitive to 5α-reductase inhibitor dutasteride.
Intermittent androgen deprivation therapy (IADT) allows prostate cancer patients a break from the side-effects of continuous androgen deprivation therapy (ADT). Although clinical studies suggest that IADT can significantly improve patient quality of life over ADT, it has not been demonstrated to improve patient survival. Recently, increased survival has been demonstrated when 5α-reductase inhibitors have been used during the off-cycle of IADT in animal xenograft tumor models LNCaP and LuCaP35. In the current study, the sensitivity of LAPC4 xenograft tumor regrowth to the 5ARI dutasteride was determined. Tumor regrowth and gene expression changes in LAPC4 tumors were compared to the previously determined response of LNCaP and LuCaP35 xenograft tumors to 5ARI treatment during the off-cycle of IADT, LAPC4, LNCaP and LuCaP35 tumors were sensitive to androgen manipulation. However, in contrast to LNCaP and LuCaP35, dutasteride treatment during testosterone-stimulated prostate regrowth did not affect tumor regrowth or the expression of androgen responsive genes. Tumor response to dutasteride during the off-cycle of IADT is variable in xenograft prostate tumor models. Future studies will be required to elucidate the mechanisms contributing to the dutasteride resistance observed in the LAPC4 model during the off-cycle.
Department of Urology, University of Pittsburgh School of Medicine Pittsburgh PA 15232, USA.
Raquel Ramos
RR
Garcia
Department of Urology, University of Pittsburgh School of Medicine Pittsburgh PA 15232, USA.
Khalid Z
KZ
Masoodi
Department of Urology, University of Pittsburgh School of Medicine Pittsburgh PA 15232, USA.
Laura E
LE
Pascal
Department of Urology, University of Pittsburgh School of Medicine Pittsburgh PA 15232, USA ; University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine Pittsburgh, PA 15232, USA.
Joel B
JB
Nelson
Department of Urology, University of Pittsburgh School of Medicine Pittsburgh PA 15232, USA ; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine Pittsburgh, PA 15232, USA ; University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine Pittsburgh, PA 15232, USA.
Zhou
Z
Wang
5α-reductase inhibitor; EAF2; LAPC4; Prostate cancer; androgen deprivation therapy