The role of signaling pathways in cervical cancer and molecular therapeutic targets

Arch Med Res. 2014 Oct;45(7):525-39. doi: 10.1016/j.arcmed.2014.10.008. Epub 2014 Nov 11.

Abstract

Cervical cancer is a public health issue in developing countries. Although the Pap smear and colposcopy remain the major strategies for detection, most cases are diagnosed in the late stages. Therefore, a major concern has been to develop early diagnostic approaches and more effective treatments. Molecular pathways that participate in cervical malignant transformation have emerged as promising directed therapeutic targets. In this review, we explore some of the major pathways implicated in cervical cancer development, including RAF/MEK/ERK, phosphatidylinositol-3 kinase (PI3K/AKT), Wnt/b-catenin, apoptosis and coupled membrane receptor signaling. We focus on the role of these pathways in cervical carcinogenesis, their alterations and the consequences of these abnormalities. In addition, the most recent preclinical and clinical data on the rationally designed target-based agents that are currently being tested against elements of these pathways are reviewed.

Keywords: Carcinogenesis; Cervical cancer; Inhibitors; Signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis
  • Cell Transformation, Neoplastic / pathology
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Molecular Targeted Therapy*
  • Phosphatidylethanolamine Binding Protein / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Wnt Proteins / antagonists & inhibitors
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / drug effects
  • Wnt Signaling Pathway / physiology*
  • beta Catenin / antagonists & inhibitors
  • beta Catenin / metabolism

Substances

  • PEBP1 protein, human
  • Phosphatidylethanolamine Binding Protein
  • Phosphoinositide-3 Kinase Inhibitors
  • Wnt Proteins
  • beta Catenin
  • Extracellular Signal-Regulated MAP Kinases