Headway and Hurdles in the Clinical Development of Dietary Phytochemicals for Cancer Therapy and Prevention: Lessons Learned from Vitamin A Derivatives
Journal Title: The AAPS Journal - Year 2014, Vol 16, Issue 2
Abstract
Accumulating epidemiologic and preclinical evidence support the pharmacologic use of a variety of dietary chemicals for the prevention and treatment of cancer. However, it will be challenging to translate these findings into routine clinical practice since phytochemicals have pleiotropic biological activities that have to be balanced for optimal efficacy without unacceptable and potentially unanticipated toxicities. Correctly matching patient populations and settings with optimal, natural product-based phytochemical therapies will require a greater understanding of the specific mechanisms underlying the efficacy, toxicity, and resistance of each agent in a variety of normal, premalignant, and malignant settings. This, in turn, necessitates continued commitment from the basic research community to guide carefully designed and informed clinical trials. The most developed class of anticancer phytochemicals consists of the derivatives of vitamin A called retinoids. Unlike other natural product chemicals currently under study, the retinoids have been extensively tested in humans. Over 30 years of clinical investigation has resulted in several disappointments, but there were some spectacular successes where certain retinoid-based protocols are now FDA-approved standard of care therapies to treat specific malignancies. Furthermore, retinoids are one of the most evaluated pharmacologic agents in the ultra-challenging setting of interventional cancer prevention. This review will summarize the development of retinoids in cancer therapy and prevention with an emphasis on currently proposed mechanisms mediating their efficacy, toxicity, and resistance.
Authors and Affiliations
Christina Y. Yim, Pingping Mao, Michael J. Spinella
Keywords
Related Articles
- EP ID EP681069
- DOI 10.1208/s12248-014-9562-2
- Views 53
- Downloads 0
Tumoricidal effects of etoposide incorporated into solid lipid nanoparticles after intraperitoneal administration in Dalton's lymphoma bearing mice
The tumoricidal effects of etoposide incorporated into lipid nanoparticles after single-dose administration were investigated in Dalton's lymphoma ascites bearing mice. Etoposide and its nanoparticle formulations were ad...
Apigenin Reactivates Nrf2 Anti-oxidative Stress Signaling in Mouse Skin Epidermal JB6 P + Cells Through Epigenetics Modifications
Nrf2 is a crucial transcription factor that controls a critical anti-oxidative stress defense system and is implicated in skin homeostasis. Apigenin (API), a potent cancer chemopreventive agent, protects against skin car...
Pharmacokinetic and Pharmacodynamic Modeling of a Monoclonal Antibody Antagonist of Glucagon Receptor in Male ob/ob Mice
Elevated basal concentrations of glucagon and reduced postprandial glucagon suppression are partly responsible for the increased hepatic glucose production seen in type 2 diabetic patients. Recently, it was demonstrated...
Varying polymer architecture to deliver drugs
Variable architecture polymers are of considerable interest for the delivery of therapeutic biopolymers, such as DNA and proteins, to their site of action. Polymers that can respond with a change in conformation to biolo...
Current Methods for Predicting Human Food Effect
Food can impact the pharmacokinetics of a drug product through several mechanisms, including but not limited to, enhancement in drug solubility, changes in GI physiology, or direct interaction with the drug. Significant...