| HOME | HELP | CONTACT US | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
a The Norris Cotton Cancer Center and Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA; b Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA
Correspondence: Konstantin H. Dragnev, M.D., Dartmouth Medical School, Department of Pharmacology and Toxicology, 7650 Remsen, Hanover, New Hampshire 03755, USA. Telephone: 603-650-1667; Fax: 603-650-1129; e-mail: Konstantin.H.Dragnev{at}dartmouth.edu
Carcinogenesis is a multistep process that converts normal cells into malignant cells. Once transformed, malignant cells acquire the ability to invade and metastasize, leading to clinically evident disease. During this continuum from normal to metastatic cells, carcinogenic steps can be arrested or reversed through pharmacological treatments, known as cancer chemoprevention. Chemoprevention strategies represent therapeutic interventions at early stages of carcinogenesis, before the onset of invasive cancer. Effective chemoprevention should reduce or avoid the clinical consequences of overt malignancies by treating early neoplastic lesions before development of clinically apparent signs or symptoms. Preclinical, clinical, and epidemiological data provide considerable support for cancer chemoprevention as an attractive therapeutic strategy. This clinical approach was validated in the recent tamoxifen randomized trial, demonstrating that a selective estrogen receptor modulator reduces the risk of breast cancer in women at high risk for this malignancy.
Derivatives of vitamin A, the retinoids, have reported activity in treating specific premalignant lesions and reducing incidence of second primary tumors in patients with prior head and neck, lung or liver cancers. Whether the retinoids will prevent primary cancers at these sites is not yet known. Notably, a carotenoid (ß-carotene) was shown as inactive in primary prevention of lung cancers in high-risk individuals. This underscores the need for relevant in vitro models to identify pathways signaling chemopreventive effects. These models should assess the activity of candidate chemoprevention agents before the conduct of large and costly prevention trials. An improved understanding of cancer prevention mechanisms should aid in the discovery of new therapeutic targets and chemoprevention agents. Ideally, these agents should have tolerable clinical toxicities suitable for chronic administration to individuals at high risk for developing primary or second cancers. This article reviews what is now known from clinical and preclinical studies about the retinoids as cancer prevention agents.
This article has been cited by other articles:
 |
|
 |
|
  H. Orita, J. Coulter, E. Tully, F. P. Kuhajda, and E. Gabrielson Inhibiting Fatty Acid Synthase for Chemoprevention of Chemically Induced Lung Tumors Clin. Cancer Res., April 15, 2008; 14(8): 2458 - 2464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ma, R. Yan, X. Zu, J.-M. Cheng, K. Rao, D.-F. Liao, and D. Cao Aldo-keto Reductase Family 1 B10 Affects Fatty Acid Synthesis by Regulating the Stability of Acetyl-CoA Carboxylase-{alpha} in Breast Cancer Cells J. Biol. Chem., February 8, 2008; 283(6): 3418 - 3423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. H. Dragnev, W. J. Petty, S. J. Shah, L. D. Lewis, C. C. Black, V. Memoli, W. C. Nugent, T. Hermann, A. Negro-Vilar, J. R. Rigas, et al. A Proof-of-Principle Clinical Trial of Bexarotene in Patients with Non-Small Cell Lung Cancer Clin. Cancer Res., March 15, 2007; 13(6): 1794 - 1800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Belosay, A. M.H. Brodie, and V. C.O. Njar Effects of Novel Retinoic Acid Metabolism Blocking Agent (VN/14-1) on Letrozole-Insensitive Breast Cancer Cells Cancer Res., December 1, 2006; 66(23): 11485 - 11493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Villano and L. A. White The Aryl Hydrocarbon Receptor-Signaling Pathway and Tissue Remodeling: Insights from the Zebrafish (Danio rerio) Model System Toxicol. Sci., July 1, 2006; 92(1): 1 - 4. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lambrot, H. Coffigny, C. Pairault, A.-C. Donnadieu, R. Frydman, R. Habert, and V. Rouiller-Fabre Use of Organ Culture to Study the Human Fetal Testis Development: Effect of Retinoic Acid J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2696 - 2703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Wang, A. J. Mendy, G. Dai, H.-R. Luo, L. He, and Y.-J. Y. Wan Retinoids Activate the RXR/SXR-Mediated Pathway and Induce the Endogenous CYP3A4 Activity in Huh7 Human Hepatoma Cells Toxicol. Sci., July 1, 2006; 92(1): 51 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Kaiser, M. Korner, A. Kappeler, and S. Aebi Retinoid receptors in ovarian cancer: expression and prognosis Ann. Onc., September 1, 2005; 16(9): 1477 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tu, D. J. Jerry, B. Pazik, and S. Smith Schneider Sensitivity to DNA Damage Is a Common Component of Hormone-Based Strategies for Protection of the Mammary Gland Mol. Cancer Res., August 1, 2005; 3(8): 435 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Rigas and K. H. Dragnev Emerging Role of Rexinoids in Non-Small Cell Lung Cancer: Focus on Bexarotene Oncologist, January 1, 2005; 10(1): 22 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Winterhalder, F. R. Hirsch, G. K. Kotantoulas, W. A. Franklin, and P. A. Bunn Jr Chemoprevention of lung cancer--from biology to clinical reality Ann. Onc., February 1, 2004; 15(2): 185 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, M. Z. Fang, J. Liao, G.-Y. Yang, Y. Nie, Y. Song, C. So, X. Xu, L.-D. Wang, and C. S. Yang Hypermethylation-Associated Inactivation of Retinoic Acid Receptor {beta} in Human Esophageal Squamous Cell Carcinoma Clin. Cancer Res., November 1, 2003; 9(14): 5257 - 5263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Richards, J. Karpilow, C. Dunn, I. Peterson, A. Maxfield, L. Zharkikh, M. Abedi, A. Hurlburt, J. Hardman, F. Hsu, et al. Genetic Selection for Modulators of a Retinoic-Acid-Responsive Reporter in Human Cells Genetics, March 1, 2003; 163(3): 1047 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G E Goodman Lung cancer * 1: Prevention of lung cancer Thorax, November 1, 2002; 57(11): 994 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lopez-Carballo, L. Moreno, S. Masia, P. Perez, and D. Barettino Activation of the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway by Retinoic Acid Is Required for Neural Differentiation of SH-SY5Y Human Neuroblastoma Cells J. Biol. Chem., July 5, 2002; 277(28): 25297 - 25304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Budhu and N. Noy Direct Channeling of Retinoic Acid between Cellular Retinoic Acid-Binding Protein II and Retinoic Acid Receptor Sensitizes Mammary Carcinoma Cells to Retinoic Acid-Induced Growth Arrest Mol. Cell. Biol., April 15, 2002; 22(8): 2632 - 2641. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | CONTACT US | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| THE ONCOLOGIST | STEM CELLS | CME | ALPHAMED PRESS JOURNALS |
