当前位置： SCI文献检索 > CURRENT CANCER DRUG TARGETS期刊下所有文献 > Novel approaches for molecular targeted therapy of breast cancer: interfering with PI3K/AKT/mTOR signaling.

Novel approaches for molecular targeted therapy of breast cancer: interfering with PI3K/AKT/mTOR signaling.

Abstract：

:Breast cancer is one of the most prevalent and devastating malignant diseases in women worldwide. Fortunately, while breast cancer incidence is still increasing, its death rate is declining. This is mainly due to early diagnosis and potent therapies such as blockade of estrogen receptor- or of ErbB2 (HER2-neu) membrane receptor signaling.In recent years, the PI3K/AKT/mTOR pathway, which transmits signals from the cell membrane into the nucleus and activates multiple oncogenic programs, has been found to play a crucial role in the regulation of breast cancer cell growth. This pathway is densely interconnected with a multitude of other important regulatory systems for glucose-,lipid- and amino acid-metabolism, for energy balance, and for autophagy. It has been found that PI3K/AKT/mTOR signaling modulates estrogen receptor function. Using transverse and feedback regulatory loops the PI3K/AKT/mTOR cascade can communicate with concurrent and with upstream systems. Thus, PI3K/AKT/mTOR is a crucial element within a complicated signaling network. This pathway is hyperactive in more than 70% of breast tumors. Hence, the protein kinases located along this route represent very attractive and promising drug targets for breast cancer therapy. Currently, numerous small molecular drugs that inhibit PI3K, AKT and/or mTOR are being developed in preclinical and clinical models of breast cancer. Some of these compounds are highly selective blocking only one particular kinase complex, whereas others interfere with two (mTORC1+mTORC2) or even three effectors (PI3K+mTORC1+mTORC2) of the pathway. Due to the many interactions with other regulatory systems, silencing of the pathway can cause unexpected results. Therefore, detailed preclinical and clinical evaluation of these compounds as single drugs and in combination is required to achieve optimal results with maximal clinical benefit and acceptable toxicity. Also, reliable biomarkers for the identification of patient subsets that will maximally benefit from PI3K/AKT/mTOR inhibition need to be developed. Thus, selective silencing of PI3K/AKT/mTOR signaling represents a promising approach for breast cancer and might prove useful when combined with other drugs. Here we review the current preclinical and clinical data and compare the potential benefits of multi- versus single-targeting PI3K/AKT/mTOR drugs.

journal_name

Curr Cancer Drug Targets

journal_title

Current cancer drug targets

authors

Grunt TW,Mariani GL

doi

10.2174/1568009611313020008

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

188-204

issue

eissn

1568-0096

issn

1873-5576

pii

CCDT-EPUB-20121121-3

journal_volume

pub_type

杂志文章,评审

在线工具

Novel approaches for molecular targeted therapy of breast cancer: interfering with PI3K/AKT/mTOR signaling.