Die and let live: harnessing BikDD to combat breast cancer stem cells

Breast Cancer Res. 2012 May 23;14(3):310. doi: 10.1186/bcr3125.

Abstract

One of the possible mechanisms contributing to the intrinsic resistance of cancer stem cells (CSCs) to conventional therapies is the inefficiency of activating the apoptotic machinery. In a recent study by Lang and colleagues, the engineered constitutively active pro-apoptotic protein BikDD, which works by inhibiting multiple Bcl-2 family members, was tested in various preclinical breast cancer models. Delivered to cells via an innovative cancer cell-specific gene-therapy approach, BikDD showed potent activity against CSCs and synergized with lapatinib and paclitaxel treatment. This novel and promising therapy warrants further translation to the clinic.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis Regulatory Proteins / pharmacology*
  • Apoptosis Regulatory Proteins / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • CD24 Antigen / drug effects
  • Female
  • Humans
  • Hyaluronan Receptors / drug effects
  • Lapatinib
  • Membrane Proteins / pharmacology*
  • Membrane Proteins / therapeutic use
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mitochondrial Proteins
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Paclitaxel / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Quinazolines / therapeutic use
  • RNA Interference
  • RNA, Small Interfering

Substances

  • Apoptosis Regulatory Proteins
  • BIK protein, human
  • CD24 Antigen
  • Hyaluronan Receptors
  • Membrane Proteins
  • Mitochondrial Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Quinazolines
  • RNA, Small Interfering
  • Lapatinib
  • Paclitaxel