The phosphoinositide 3-kinase pathway in human cancer: genetic alterations and therapeutic implications.
The phosphoinositide 3-kinase pathway in human cancer: genetic alterations and therapeutic implications.
复制标题
人类癌症中的磷酸肌醇3-激酶途径：遗传改变和治疗意义。
DOI：
10.2174/138920207782446160
复制
发表时间：
2007-08
期刊：
影响因子：
2.6
通讯作者：
Guerreiro AS
中科院分区：
文献类型：
--
作者：
Arcaro A;Guerreiro AS
磷酸肌醇3-激酶（PI 3 K）通路在人类癌症中经常被激活，并且代表了基于小分子抑制剂的治疗的有吸引力的靶标。PI 3 K亚型在由细胞表面受体（包括受体酪氨酸激酶（RTK）和G蛋白偶联受体（GPCR））激活的信号转导事件中起重要作用。在人类中存在八种已知的PI 3 K同种型，其被细分为三类（I-III）。因此，PI 3 K显示出相当大的多样性，并且仍然不清楚该家族中的哪些激酶应该在癌症中被靶向。IA类PI 3 K包括p110α、p110β和p110δ亚型，它们与活化的RTK相关。在人类癌症中，最近的报告描述了编码p110α的PIK 3CA基因的激活突变，以及磷酸酶和张力蛋白同源物（PTEN）基因（一种PI 3 K通路的肿瘤抑制剂和拮抗剂）的失活突变。在癌症中描述的PIK 3CA突变组成性激活p110α，当在细胞中表达时驱动致癌转化。此外，这些突变引起下游信号分子的组成性激活，例如Akt/蛋白激酶B（PK B）、哺乳动物雷帕霉素靶标（mTOR）和核糖体蛋白S6激酶（S6 K），其通常在癌细胞中观察到。除了p110α，PI 3 K家族的其他亚型也可能在人类癌症中发挥作用，尽管它们的个体功能仍有待精确鉴定。在这篇综述中，我们将讨论的证据表明，个人PI 3 K亚型在人类癌症和他们的潜力，在这种情况下作为药物靶点。
The phosphoinositide 3-kinase (PI3K) pathway is frequently activated in human cancer and represents an attractive target for therapies based on small molecule inhibitors. PI3K isoforms play an essential role in the signal transduction events activated by cell surface receptors including receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs). There are eight known PI3K isoforms in humans, which have been subdivided into three classes (I-III). Therefore PI3Ks show considerable diversity and it remains unclear which kinases in this family should be targeted in cancer. The class IA of PI3K comprises the p110α, p110β and p110δ isoforms, which associate with activated RTKs. In human cancer, recent reports have described activating mutations in the PIK3CA gene encoding p110α, and inactivating mutations in the phosphatase and tensin homologue (PTEN) gene, a tumour suppressor and antagonist of the PI3K pathway. The PIK3CA mutations described in cancer constitutively activate p110α and, when expressed in cells drive oncogenic transformation. Moreover, these mutations cause the constitutive activation of downstream signaling molecules such as Akt/protein kinase B (PKB), mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (S6K) that is commonly observed in cancer cells. In addition to p110α, the other isoforms of the PI3K family may also play a role in human cancer, although their individual functions remain to be precisely identified. In this review we will discuss the evidence implicating individual PI3K isoforms in human cancer and their potential as drug targets in this context.
登录
查看更多内容
影响因子：
8
作者：
Altomare, DA;You, HH;Testa, JR
通讯作者：
Testa, JR
DOI：
10.1073/pnas.95.25.14950
发表时间：
1998-12-08
影响因子：
11.1
作者：
Aoki, M;Batista, O;Vogt, PK
通讯作者：
Vogt, PK
DOI：
10.1073/pnas.0405454101
发表时间：
2004-09-14
影响因子：
11.1
作者：
Aoki, M;Hao, J;Vogt, PK
通讯作者：
Vogt, PK
影响因子：
4.8
作者：
Arcaro, A;Volinia, S;Waterfield, MD
通讯作者：
Waterfield, MD
DOI：
10.1073/pnas.011528498
发表时间：
2001-01-02
影响因子：
11.1
作者：
Aoki, M;Blazek, E;Vogt, PK
通讯作者：
Vogt, PK