Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health.
Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health.
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DOI：
10.18632/oncotarget.240
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
McCubrey JA
中科院分区：
文献类型：
--
作者：
Chappell WH;Steelman LS;Long JM;Kempf RC;Abrams SL;Franklin RA;Bäsecke J;Stivala F;Donia M;Fagone P;Malaponte G;Mazzarino MC;Nicoletti F;Libra M;Maksimovic-Ivanic D;Mijatovic S;Montalto G;Cervello M;Laidler P;Milella M;Tafuri A;Bonati A;Evangelisti C;Cocco L;Martelli AM;McCubrey JA
Ras/Raf/MEK/ERK和PI 3 K/PTEN/Akt/mTOR级联反应通常通过上游信号分子如受体酪氨酸激酶（RTK）的遗传改变来激活。这些途径的组成部分Ras、B-Raf、PI 3 K和PTEN也通过突变激活/失活。这些途径对增殖、凋亡和分化途径具有深远的影响。这些途径的失调可导致化疗药物抗性、癌症起始细胞（CIC）的增殖和过早衰老。本文将评估最近描述的MEK，PI 3 K，Akt和mTOR抑制剂在恶性细胞增殖，抑制CIC，细胞衰老和预防衰老中的潜在用途。Ras/Raf/MEK/ERK和Ras/PI 3 K/PTEN/Akt/mTOR通路在正常和恶性细胞生长的调节中起关键作用。靶向这些通路的抑制剂具有许多潜在用途，如抑制癌症、增殖性疾病以及衰老。
The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of these pathways can contribute to chemotherapeutic drug resistance, proliferation of cancer initiating cells (CICs) and premature aging. This review will evaluate more recently described potential uses of MEK, PI3K, Akt and mTOR inhibitors in the proliferation of malignant cells, suppression of CICs, cellular senescence and prevention of aging. Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways play key roles in the regulation of normal and malignant cell growth. Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging.
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DOI：
10.18632/aging.100040
发表时间：
2009-04-20
期刊：
Aging
影响因子：
--
作者：
Blagosklonny MV;Hall MN
通讯作者：
Hall MN
影响因子：
4.3
作者：
Blagosklonny, Mikhail V.
通讯作者：
Blagosklonny, Mikhail V.
影响因子：
4.3
作者：
Blagosklonny, Mikhail V.
通讯作者：
Blagosklonny, Mikhail V.
DOI：
10.18632/aging.100149
发表时间：
2010-05
期刊：
Aging
影响因子：
--
作者：
Blagosklonny MV
通讯作者：
Blagosklonny MV
影响因子：
4.3
作者：
Anisimov, Vladimir N.;Berstein, Lev M.;Semenchenko, Anna V.
通讯作者：
Semenchenko, Anna V.