Prostate cancer: potential targets of anti-proliferative and apoptotic signaling pathways.

Prostate cancers are genetically and phenotypically heterogenous. The heterogeneous nature of prostate cancer may be a consequence of mutations in different cell types (basal stem, transit amplifying or luminal cells) resulting in different malignant maturation pathways. One consistent characterization of these cancers, however, is their eventual progression to a hormonal refractory state. The development of effective novel therapeutic strategies requires an understanding of the mechanisms for the development of such a refractory state. Targeting proliferative and survival pathways provides a rationale for drug design and development for hormone refractory prostate cancer. Prostate cancer cells, however, develop an enhanced redundancy in downstream survival signaling. Hence, new combinational therapies must be developed with the understanding that compensatory mechanisms evolve under selective pressure.

[1]  T. Stamey,et al.  Zonal Distribution of Prostatic Adenocarcinoma: Correlation with Histologic Pattern and Direction of Spread , 1988, The American journal of surgical pathology.

[2]  R. Millikan,et al.  Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumors with observations in androgen-independent prostate cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  M. Campbell,et al.  Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. , 1992, Cancer research.

[4]  J. Hicks,et al.  Hypermethylation of the human glutathione S-transferase-pi gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the prostate: a detailed study using laser-capture microdissection. , 2003, The American journal of pathology.

[5]  G. Jenster Ligand‐independent activation of the androgen receptor in prostate cancer by growth factors and cytokines , 2000, The Journal of pathology.

[6]  S. Steinberg,et al.  A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients with androgen-independent prostate cancer. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[7]  J T Arnold,et al.  Mechanisms involved in the progression of androgen-independent prostate cancers: it is not only the cancer cell's fault. , 2002, Endocrine-related cancer.

[8]  A. Jemal,et al.  Cancer Statistics, 2004 , 2004, CA: a cancer journal for clinicians.

[9]  Marty W. Mayo,et al.  TNF- and Cancer Therapy-Induced Apoptosis: Potentiation by Inhibition of NF-κB , 1996, Science.

[10]  M. Gleave,et al.  Intermittent androgen suppression in prostate cancer: an update of the Vancouver experience. , 2003, The Canadian journal of urology.

[11]  Karen L. Siedlecki,et al.  Phase I trial of BCL-2 antisense oligonucleotide (G3139) administered by continuous intravenous infusion in patients with advanced cancer. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[12]  M. Shen,et al.  Molecular genetics of prostate cancer. , 2000, Genes & development.

[13]  J. Isaacs,et al.  Enhanced Redundancy in Akt and Mitogen-activated Protein Kinase-induced Survival of Malignant versus Normal Prostate Epithelial Cells , 2004, Cancer Research.

[14]  A. D. De Marzo,et al.  Is the Achilles' heel for prostate cancer therapy a gain of function in androgen receptor signaling? , 2003, The Journal of clinical endocrinology and metabolism.

[15]  J. Isaacs,et al.  The biology of hormone refractory prostate cancer. Why does it develop? , 1999, The Urologic clinics of North America.

[16]  A. Weeraratna,et al.  Pan-trk inhibition decreases metastasis and enhances host survival in experimental models as a result of its selective induction of apoptosis of prostate cancer cells. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[17]  A. Deitch,et al.  Very frequent p53 mutations in metastatic prostate carcinoma and in matched primary tumors , 1998, Cancer.

[18]  J. Isaacs,et al.  A history of prostate cancer treatment , 2002, Nature Reviews Cancer.

[19]  R. Vessella,et al.  Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Carducci,et al.  Complete androgen blockade for prostate cancer: what went wrong? , 2000, The Journal of urology.

[21]  D. S. Coffey,et al.  Adaptation versus selection as the mechanism responsible for the relapse of prostatic cancer to androgen ablation therapy as studied in the Dunning R-3327-H adenocarcinoma. , 1981, Cancer research.

[22]  J. Isaacs,et al.  Conversion from a paracrine to an autocrine mechanism of androgen-stimulated growth during malignant transformation of prostatic epithelial cells. , 2001, Cancer research.

[23]  W. Isaacs,et al.  Androgen receptor outwits prostate cancer drugs , 2004, Nature Medicine.

[24]  J. Nelson,et al.  Endothelin-1 as a Target for Therapeutic Intervention in Prostate Cancer , 2002, Investigational New Drugs.

[25]  H. Scher,et al.  Prostate cancer: a dynamic illness with shifting targets. , 2003, The Lancet. Oncology.

[26]  P. LoRusso Phase I studies of ZD1839 in patients with common solid tumors. , 2003, Seminars in oncology.

[27]  H. Lilja,et al.  Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer. , 2003, Journal of the National Cancer Institute.

[28]  D. Amanatullah,et al.  Cell-cycle dysregulation and the molecular mechanisms of prostate cancer. , 2000, Frontiers in bioscience : a journal and virtual library.

[29]  H. Scher,et al.  Flutamide withdrawal syndrome: its impact on clinical trials in hormone-refractory prostate cancer. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  J. Nelson,et al.  Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: a randomized, phase II, placebo-controlled trial. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  J. Isaacs,et al.  In vitro culturing and characteristics of transit amplifying epithelial cells from human prostate tissue , 2004, Journal of cellular biochemistry.

[32]  E. Small,et al.  Docetaxel, estramustine, plus trastuzumab in patients with metastatic androgen-independent prostate cancer. , 2001, Seminars in oncology.

[33]  F. Saad,et al.  Effects of atrasentan on disease progression and biological markers in men with metastatic hormone-refractory prostate cancer: Phase 3 study. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.