Molecular biology of breast cancer stem cells: potential clinical applications.
Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy.
Department of Radiation Oncology, University of Arizona, N. Campbell Ave, Tucson, AZ 85724-5081, USA. NamPhong.Nguyen@yahoo.com
Nam P
NP
Nguyen
Fabio S
FS
Almeida
Alex
A
Chi
Ly M
LM
Nguyen
Deirdre
D
Cohen
Ulf
U
Karlsson
Vincent
V
Vinh-Hung
D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D008967:Molecular Biology / Q000379:methods / Q000639:trends; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D050504:Oncolytic Viruses / Q000378:metabolism; D011836:Radiation Tolerance / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
D000970:Antineoplastic Agents