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The PIM kinases in hematological cancers
Yesid Alvarado1, Francis J Giles, Ronan T Swords
1Department of Hematology/Oncology, Cancer Therapy & Research Center, The University of Texas Health Science Center San Antonio, 7979 Wurzbach Road, MC8232, San Antonio, 78229, TX, USA.
Expert Review of Hematology
|January 26, 2012
Summary
PIM kinases are overexpressed in blood cancers, driving tumor growth and drug resistance. New small-molecule inhibitors targeting these constitutively active kinases show promise for treating hematologic malignancies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- PIM kinases (PIM1, PIM2, PIM3) are serine/threonine protein kinases involved in cell survival, proliferation, and drug resistance.
- Overexpression of PIM kinases is observed in various hematopoietic tumors, supporting malignant cell growth and survival.
- These kinases are constitutively active due to the absence of a regulatory domain and act as effectors of oncoproteins.
Purpose of the Study:
- To review PIM kinases as therapeutic targets in hematologic malignancies.
- To highlight the role of PIM kinases in promoting cancer progression and drug resistance.
- To discuss the development of small-molecule PIM kinase inhibitors.
Main Methods:
- Review of preclinical and clinical studies on PIM kinase inhibitors.
- Analysis of structural information, including crystallography studies of PIM kinases.
- Examination of PIM kinase roles in signal transduction and cancer biology.
Main Results:
- PIM kinases contribute to malignant cell growth, survival, and resistance to therapies like rapamycin.
- Unique structural features, such as a hinge region, create a specific ATP-binding pocket.
- Potent small-molecule PIM kinase inhibitors have been developed, showing promising preclinical activity.
Conclusions:
- PIM kinases represent a promising therapeutic target for hematologic malignancies.
- Novel small-molecule inhibitors targeting PIM kinases are under clinical investigation.
- Targeting PIM kinases offers a potential strategy to overcome drug resistance in blood cancers.
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