Abstract: A treatment for prostate cancer using cyclin-dependent kinase inhibitors (CKIs) and a method of determining patient sensitivity to such CKIs is provided. The effects of cyclin-dependent kinase inhibitors on the survival of prostate cancer cells was examined. Roscovitine, R-roscovitine, and CGP74514A were shown to induce the apoptosis of LNCaP and LNCaP-Rf cells, both of which express wild-type p53. The cyclin-dependent kinase inhibitors of the present invention induce the mitochondria-mediated apoptosis of prostate cancer cells by a dual mechanism: p53 accumulation and XIAP depletion.

Abstract: A treatment for prostate cancer using cyclin-dependent kinase inhibitors is provided. The effects of cyclin-dependent kinase inhibitors on the survival of prostate cancer cells was examined. Roscovitine, R-roscovitine, and CGP74514A were shown to induce the apoptosis of LNCaP and LNCaP-Rf cells, both of which express wild-type p53. The cyclin-dependent kinase inhibitors of the present invention induce the mitochondria-mediated apoptosis of prostate cancer cells by a dual mechanism: p53 accumulation and XIAP depletion.

Abstract: The subject invention pertains to a transgenic animal model for tumorigenesis having a genome comprising a ras transgene and which is heterozygous or homozygous for a null p27 gene, and methods of using such animal to screen compounds or evaluate treatments for oncogenic and antitumor activity. The subject invention further concerns a transgenic mouse comprising a ras transgene and which has a genome that is wild-type p27+/+, and wherein the mouse has an FVB/N and C57BL/6X 129 genetic background; and methods of using such transgenic mice to screen compounds or evaluate treatments for oncogenic or antitumor activity. Advantageously, the female animals of the subject invention are fertile and capable of nursing their young. The subject invention also pertains to in vitro systems including isolated cells or tissues of animal models for tumorigenesis, which can be used to screen compounds and treatments for oncogenic and antitumor activity.

Abstract: A treatment for cancer using a combination therapy including an inhibitor of the PI3K/Akt pathway in combination with roscovitine. It is shown that the combination of roscovitine and API-2 (Triciribine) or roscovitine and LY294002 induce the apoptosis of androgen-dependent (LNCaP) and androgen-independent (PC3) prostate cancer cells. Two important results have been observed. First, cells that respond to roscovitine alone (LNCaP) initiate apoptosis sooner when co-treated. Second, cells that do not respond to roscovitine alone (PC3) apoptose when co-treated, although with delayed kinetics. In the absence of roscovitine, AKT inhibitors had no effect on LNCaP or PC3 survival, and in both cell lines, the combined treatment activated the mitochondrial pathway of apoptosis. Importantly, normal epithelial cells (RPWE) remained viable in the presence of roscovitine and AKT inhibitors.

Abstract: The subject invention pertains to a transgenic animal model for tumorigenesis having a genome comprising a ras transgene and which is heterozygous or homozygous for a null p27 gene, and methods of using such animal to screen compounds or evaluate treatments for oncogenic and antitumor activity. The subject invention further concerns a transgenic mouse comprising a ras transgene and which has a genome that is wild-type p27+/+, and wherein the mouse has an FVB/N and C57BLU6 X 129 genetic background; and methods of using such transgenic mice to screen compounds or evaluate treatments for oncogenic or antitumor activity. Advantageously, the female animals of the subject invention are fertile and capable of nursing their young. The subject invention also pertains to in vitro systems including isolated cells or tissues of animal models for tumorigenesis, which can be used to screen compounds and treatments for oncogenic and antitumor activity.