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Pharmacological targets of breast cancer stem cells: a review

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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.

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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

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Authors and Affiliations

  1. Department of Pharmacology, JSS College of Pharmacy (Jagadguru Sri Shivarathreeshwara University), Rocklands, Udhagamandalam, Tamil Nadu, 643001, India

    Sai Kiran S. S. Pindiprolu, Praveen T. Krishnamurthy & Pavan Kumar Chintamaneni

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  1. Sai Kiran S. S. Pindiprolu
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  2. Praveen T. Krishnamurthy
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  3. Pavan Kumar Chintamaneni
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Correspondence to Praveen T. Krishnamurthy.

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Pindiprolu, S.K.S.S., Krishnamurthy, P.T. & Chintamaneni, P.K. Pharmacological targets of breast cancer stem cells: a review. Naunyn-Schmiedeberg's Arch Pharmacol 391, 463–479 (2018). https://doi.org/10.1007/s00210-018-1479-3

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  • DOI: https://doi.org/10.1007/s00210-018-1479-3

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