Pharmacological targets of breast cancer stem cells: a review

  • Sai Kiran S. S. Pindiprolu
  • Praveen T. Krishnamurthy
  • Pavan Kumar Chintamaneni
Review

Abstract

Breast cancers contain small population of tumor-initiating cells called breast cancer stem cells (BCSCs), which are spared even after chemotherapy. Recently, BCSCs are implicated to be a cause of metastasis, tumor relapse, and therapy resistance in breast cancer. BCSCs have unique molecular mechanisms, which can be targeted to eliminate them. These include surface biomarkers, proteins involved in self-renewal pathways, drug efflux transporters, apoptotic/antiapoptotic proteins, autophagy, metabolism, and microenvironment regulation. The complex molecular mechanisms behind the survival of BCSCs and pharmacological targets for elimination of BCSCs are described in this review.

Keywords

Breast cancer Breast cancer stem cells Tumor relapse Metastasis Chemoresistance 

Abbreviations

ABC

ATP-binding cassette

ATM

Ataxia telangiectasia-mutated serine/threonine kinase

Bcl2

B cell lymphoma 2

BCRP

Breast cancer resistance protein

BCSCs

Breast cancer stem cells

BIK

Bcl2 interacting killer

Bmi-1

B cell-specific Moloney murine leukemia virus integration site 1

BMP2

Bone morphogenetic protein 2

CAIX

Carbonic anhydrase-IX

CAT

Catalase

CSL

CBF-1/RBPJ-κ in Homo sapiens/Mus musculus, respectively, Suppressor of hairless in Drosophila melanogaster, Lag-1 in Caenorhabditis elegans

CDK

Cyclin-dependent kinases

ChKs

Checkpoint kinases

c-myc

C-terminus of myc protein

DHh

Desert Hedgehog

DLL4

Delta-like 4 ligand

DOX

Doxorubicin

DRs

Death receptors

EMT

Epithelial-to-mesenchymal transition

EpICD

EpCAM intracellular domain

FAS

Fatty acid synthase

FTC

Fumitremorgin C

Gl

Glioma-associated oncogene

GLUT

Glucose transporter

GM-CSF

Granulocyte-macrophage colony-stimulating factor

GPO

Glutathione peroxidase

GSK-3β

Glycogen synthase kinase 3 β

HDR

Homology-directed recombination

Hh

Hedgehog

HK

Hexose kinase

IHh

Indian Hedgehog

IL

Interleukin

JAK

Janus kinase

LRP

Low-density lipoprotein-related receptor

MAML

Mastermind like

m-TOR

Mammalian target of rapamycin

Nanog

Gene named after the Tír na nÓg legend

NHEJ

Nonhomologous end joining

NICD

Notch intracellular domain

non-BCSCs

Non-breast cancer stem cells or bulk tumor cells

Oct-4

Octamer-binding transcription factor

PDZ

Disheveled PDZ domain

PI3-k

Phosphoinositide 3-kinase

PTEN

Phosphatase and tensin homolog

SCs

Normal stem cells

SHh

Sonic Hedgehog

SMADs

Homologs of Sma and MAD proteins

Smo

Smoothened

SOD

Superoxide dismutase

SOX

Sry-related HMG box

STAT

Signal transducers and activators of transcription

STAT3

Signal transducer and activator of transcription factor 3

TGF-β

Transforming growth factor-β

TR

Thio-redoxin

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Sai Kiran S. S. Pindiprolu
    • 1
  • Praveen T. Krishnamurthy
    • 1
  • Pavan Kumar Chintamaneni
    • 1
  1. 1.Department of PharmacologyJSS College of Pharmacy (Jagadguru Sri Shivarathreeshwara University)UdhagamandalamIndia

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