Targeting PI3K signaling in cancer: Challenges and advances

被引：86

作者：

De Santis, Maria Chiara ^{[1
]}

Gulluni, Federico ^{[1
]}

Campa, Carlo Cosimo ^{[2
]}

Martini, Miriam ^{[1
]}

Hirsch, Emilio ^{[1
]}

机构：

[1] Univ Torino, Dept Mol Biotechnol & Hlth Sci, Turin, Italy

[2] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER | 2019年 / 1871卷 / 02期

关键词：

PI3K; Pathway inhibitors; Systemic toxicity; Combination therapy; PHOSPHATIDYLINOSITOL; 3-KINASE; PHOSPHOINOSITIDE; DOSE-ESCALATION; DUAL INHIBITOR; PHASE IB; IDELALISIB; PATHWAY; KINASE; COMBINATION; GROWTH;

D O I：

10.1016/j.bbcan.2019.03.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The key role of phosphoinositide 3-kinase (PI3K) pathway in different cellular processes and several disorders, together with the presence of targetable proteins, opened the way to promising studies for the development of small molecule inhibitors. Despite the high expectation, the shift of PI3K inhibitors to the clinic met several limitations due to the emergence of dose-limiting, on-target adverse effects. In this review, we will summarize the main issues and recent advances in PI3K inhibitors clinical trials. The effort to develop isoform-specific inhibitors, together with novel therapeutic strategies aimed at reducing the toxicity and adverse effects, opened a new promising era for PI3K inhibitors. In addition, we will focus on the recent emergence of class II and III PI3K inhibitors, which helped to define their class I non-redundant role.

引用

页码：361 / 366

页数：6

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