Drugs interfering with apoptosis in breast cancer

Curr Pharm Des. 2011;17(3):272-83. doi: 10.2174/138161211795049723.

Abstract

Apoptosis plays an important role in development, growth, differentiation, altered gravity conditions, tissue homeostasis, immune defense, and cancer. It can be initiated by external signals via death receptors, but may also emerge from mitochondria. Today most of the key players in cellular apoptosis regulation are identified and can be targeted by therapeutic strategies. In this review we focus on recent development of drugs, which interfere with apoptosis and are currently used or tested for treatment of breast cancer. These novel agents include those targeting the extrinsic pathway such as Fas, tumor necrosis factor-alpha and tumor necrosis factor related apoptosis-inducing ligand, as well as drugs targeting the intrinsic Bcl-2 family pathway, or drugs inhibiting repair enzymes such as Poly (ADP-ribose) polymerase (PARP) inhibitors. Their function will be explained, their role in tumor biology and actual clinical studies will be discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / physiopathology*
  • Caspases / metabolism
  • Drug Discovery*
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology
  • TNF-Related Apoptosis-Inducing Ligand / therapeutic use
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / therapeutic use
  • Tumor Suppressor Protein p53 / metabolism
  • fas Receptor / metabolism

Substances

  • Antineoplastic Agents
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • fas Receptor
  • Poly(ADP-ribose) Polymerases
  • Caspases