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Inhibitors of phosphatidylinositol signalling as antiproliferative agents
Abstract:
Intracellular signalling pathways mediating the effects of oncogenes on cell growth and transformation offer novel targets for the development of anticancer drugs. With this approach it may be sufficient to target a component of the signalling pathway activated by the oncogene rather than the oncogene product itself. Phosphatidylinositol (PtdIns) is a key component of two growth factor signalling pathways. It acts as a substrate for PtdIns specific phospholipase C (PtdInsPLC) and for PtdIns-3-kinase. In this review the antiproliferative properties of some inhibitors of PtdInsPLC and PtdIns-3-kinase are considered. There are some compounds already in clinical trial as anticancer drugs that may act by inhibiting PtdIns signalling, as well as several compounds in preclinical development. Some problems that may be encountered in developing this new class of anticancer drugs are discussed.
Insights
Targeting intracellular signalling pathways, such as phosphatidylinositol (PtdIns) pathways, offers a novel strategy for anticancer drug development. Inhibitors of PtdIns-3-kinase and PtdIns specific phospholipase C show antiproliferative effects.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Oncogenes drive cell growth and transformation through intracellular signaling pathways.
- Phosphatidylinositol (PtdIns) is crucial in growth factor signaling, acting as a substrate for PtdIns-3-kinase and PtdIns specific phospholipase C (PtdInsPLC).
Purpose of the Study:
- To review the antiproliferative properties of inhibitors targeting PtdIns-3-kinase and PtdInsPLC.
- To discuss the potential of targeting PtdIns signaling pathways for novel anticancer drug development.
Main Methods:
- Review of existing literature on PtdIns signaling pathways.
- Analysis of compounds inhibiting PtdInsPLC and PtdIns-3-kinase.
- Consideration of compounds in clinical trials and preclinical development.
Main Results:
- Inhibitors of PtdInsPLC and PtdIns-3-kinase demonstrate antiproliferative effects.
- Several compounds targeting PtdIns signaling are in clinical trials or preclinical development for cancer treatment.
Conclusions:
- Targeting components of oncogene-activated signaling pathways, like PtdIns signaling, is a promising anticancer drug development strategy.
- Challenges in developing this new class of anticancer drugs are acknowledged.