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New Molecular Therapeutic Interventions: The Case of Breast Cancers

  • Véronique Marsaud
  • Jack-Michel Renoir
Chapter
Part of the Macromolecular Anticancer Therapeutics book series (CDD&D)

Abstract

Despite enormous progresses made in breast cancer therapy, this disease remains one of those leading to higher number of deaths in western countries. Like other cancers, breast cancers can be treated by classical chemotherapeutic drugs but these molecules, following their administration, largely distribute in the whole body and provoke severe unwanted side effects due to poor specificity. Breast cancers have been classified into two large categories: those which are hormone dependent and those which are hormone independent. Estradiol and estrogenic compounds are responsible for the hormone-dependent growth of breast cancers through activation of the estrogen receptor α (ERα)-transactivation pathway (receptors are macromolecules involved in chemical signaling between and within the cells). ERβ is another ER species which counteracts ERα and is supposed to act as a tumor suppressor. Both ERs’ functions are inhibited by antiestrogens: a number of new molecules targeting directly or indirectly one or both of the above forms of ERs are in various phases of clinical development (proteasome inhibitors, inhibitors suppressing the chaperone activity of the heat shock protein hsp90, or the activity of farnesyl transferases, or histone deacetylases) or inhibitors of the Pi3kinase/Akt pathway and humanized antibodies. Metastasis is the major concern in breast cancer therapy which involves a small population of stem cells present in tumors representing crucial target to be attained. Thus, the potential of various new molecular therapeutic interventions in targeting this estradiol receptor family for the treatment of breast cancer will be discussed in this chapter.

Keywords

Breast Cancer Breast Cancer Estrogen Receptor Hyaluronic Acid Aromatase Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

Ab

Antibody

ABC

Advanced breast cancer

AE

Antiestrogen

AF

Activating function

AI

Aromatase inhibitor

AIB1

Amplified in BC

Akt/PKB

Protein kinases B

ATP

Adenosine triphosphate

BC

Breast cancer

CARM1

Coactivator-associated arginine methyltransferase 1

CBP

CREB-binding protein

CDK

Cyclin-dependent kinase

CKI

Cyclin-dependent kinase inhibitor

E2

Estradiol

EGFR

Epidermal growth factor receptor

ER

Estrogen receptor

Erb-B2

Erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma-derived oncogene homolog

FTI

Farnesyl transferase inhibitor

HAT

Histone acetyl transferase

HA

Hyaluronic acid

HDAC

Histone deacetylase

Hip

Hsp70-interacting protein

Hop

Hsp70-hsp90 organizing protein

IGF1-R

Insulin-like growth factor 1 receptor

IGFR

Insulin growth factor receptor

LABC

Locally advanced BC

MAPK

Mitogen-activated protein kinase

MBC

Metastatic breast cancer

Mdm2

Mouse double minute 2

MNAR

Modulator of non-genomic action of estrogen receptor

MPS

Mononuclear phagocyte system

mTOR

Mammalian target of rapamycin

N-CoR

Nuclear receptor corepressor

OH-T

4-Hydroxytamoxifen

pCAF

Protein-associated factor

PGC-1

PPARγ coactivator-1

Pi3-K

Phosphatidylinositol-3 kinase

PKA

Protein kinase A

PKC

Protein kinase C

PR

Progesterone receptor

RU

RU 58668 or (11β-[4-[5-[4,4,5,5,5-pentafluoropentyl)sulfonyl]pentyloxy]phenyl]-estra-1,3,5(10)-triene-3,17β-diol

SERD

Selective estrogen receptor disruptor

SERM

Selective estrogen receptor modulator

SHBG or SBP

Sex hormone-binding globulin or sex steroid-binding plasma protein

SMRT

Silencing mediator for retinoid and thyroid hormone receptor

Src

Sarcoma virus tyrosine kinase

SRC-1

Steroid receptor coactivator 1

Tam

Tamoxifen

TGF

Tumor growth factor

TKI

Tyrosine kinase inhibitor; SIRT, sirtuin

VEGF

Vascular endothelial growth factor

Notes

Acknowledgments

Supported by The Ligue Nationale contre le Cancer – Indre and Hauts de Seine departments committees [to Jack-Michel Renoir]

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Véronique Marsaud
    • 1
  • Jack-Michel Renoir
    • 1
  1. 1.CNRS, UMR 8612, Physico-Chimie, Pharmacotechnie, BiopharmaciePharmacologie Cellulaire et Moléculaire des AnticancéreuxChâtenay-MalabryFrance

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