Abstract
Ovarian cancer is the most lethal gynecological malignancy. Cisplatin and its derivatives are first-line chemotherapeutics, and their resistance is a major hurdle in successful ovarian cancer treatment. Understanding the molecular dysregulation underlying chemoresistance is important for enhancing therapeutic outcome. Here, we review two established pathways in cancer chemoresistance. p53 is a major tumor suppressor regulating proliferation and apoptosis, and its mutation is a frequent event in human malignancies. The PI3K/Akt axis is a key oncogenic pathway regulating survival and tumorigenesis by controlling several tumor suppressors, including p53. The interplay between these pathways is well established, although the oncogenic phosphatase PPM1D adds a new layer to this intricate relationship and provides new insights into the processes determining cell fate. Inhibition of the PI3K/Akt pathway by functional food compounds as an adjunct to chemotherapeutics may tip the balance in favor of apoptosis rather than survival, enhancing therapeutic efficacy, and reducing side effects.
© 2012 New York Academy of Sciences.
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Animals
-
Anticarcinogenic Agents / adverse effects
-
Anticarcinogenic Agents / metabolism
-
Anticarcinogenic Agents / pharmacology
-
Anticarcinogenic Agents / therapeutic use
-
Antineoplastic Agents / adverse effects*
-
Antineoplastic Agents / metabolism
-
Antineoplastic Agents / pharmacology
-
Antineoplastic Agents / therapeutic use*
-
Antineoplastic Agents, Phytogenic / adverse effects
-
Antineoplastic Agents, Phytogenic / metabolism
-
Antineoplastic Agents, Phytogenic / pharmacology
-
Antineoplastic Agents, Phytogenic / therapeutic use
-
Apoptosis / drug effects
-
Cell Survival / drug effects
-
DNA Damage
-
Drug Resistance, Neoplasm*
-
Female
-
Food, Fortified
-
Functional Food
-
Humans
-
Molecular Targeted Therapy*
-
Ovarian Neoplasms / drug therapy*
-
Ovarian Neoplasms / metabolism*
-
Ovarian Neoplasms / prevention & control
-
Phosphoprotein Phosphatases / metabolism
-
Protein Kinase Inhibitors / adverse effects
-
Protein Kinase Inhibitors / metabolism
-
Protein Kinase Inhibitors / pharmacology
-
Protein Kinase Inhibitors / therapeutic use
-
Protein Phosphatase 2C
-
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
-
Proto-Oncogene Proteins c-akt / metabolism
-
Signal Transduction / drug effects
-
Tumor Suppressor Protein p53 / metabolism
Substances
-
Anticarcinogenic Agents
-
Antineoplastic Agents
-
Antineoplastic Agents, Phytogenic
-
Protein Kinase Inhibitors
-
TP53 protein, human
-
Tumor Suppressor Protein p53
-
Proto-Oncogene Proteins c-akt
-
PPM1D protein, human
-
Phosphoprotein Phosphatases
-
Protein Phosphatase 2C