Accession Number : ADA549157


Title :   Preclinical Studies of Signaling Pathways in a Mutant Mouse Model of Hormone-Refractory Prostate Cancer


Descriptive Note : Final rept. 28 Jan 2008-27 Jan 2011


Corporate Author : COLUMBIA UNIV NEW YORK


Personal Author(s) : Abate-Shen, Corry


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a549157.pdf


Report Date : Feb 2011


Pagination or Media Count : 59


Abstract : We have been investigating targeted therapies for the treatment of advanced prostate cancer using a genetically-engineered mouse model of the disease. Based on previous studies, we performed pre-clinical studies to examine the consequences of combinatorial inhibition of these signaling pathways for prostate tumorigenesis an androgen-independence. We found that combination therapy using Rapamycin, an inhibitor of mTOR, and PD0325901, a MEK inhibitor, is potently anti-tumorigenic in Nkx3.1; Pten mutant mice, particularly in contexts of limiting androgens. Furthermore, we find that these signaling pathways are coordinately de-regulated during prostate cancer progression in humans, as evident by our comprehensive analyses of their status in human tissue microarrays. Based on these pre-clinical studies in the mutant mice, and our supporting data from human prostate cancer, we propose that combination therapy targeting the Akt/mTOR kinase and Erk Map kinase signaling pathways may be effective for treatment of a broad spectrum of patients with advanced prostate cancer, particularly when used in conjunction with androgen deprivation therapy.


Descriptors :   *HORMONES , *PHOSPHORUS TRANSFERASES , *PROSTATE CANCER , ANATOMICAL MODELS , ANDROGENS , CLINICAL MEDICINE , GROWTH(PHYSIOLOGY) , HUMAN BODY , INHIBITORS , MICE , NEOPLASMS , PROSTATE GLAND , TARGETING , THERAPY , TISSUES(BIOLOGY)


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE