Why target PIM1 for cancer diagnosis and treatment?

作者：Magnuson, Nancy S^*; Wang, Zeping; Ding, Gang; Reeves, Raymond

来源：Future Oncology, 2010, 6(9): 1461-1478.

DOI：10.2217/FON.10.106

• antiapoptotic
• biomarker cell cycle arrest
• DNA repair drug target
• genomic instability
• PIM1 serine/threonine kinase
• SGI-1776

The highly conserved proto-oncogenic protein PIM1 is an unusual serine or threonine kinase, in part because it is constitutively active. Overexpression of PIM1 experimentally leads to tumor formation in mice, while complete knockout of the protein has no observable phenotype. It appears to contribute to cancer development in three major ways when it is overexpressed: by inhibiting apoptosis, by promoting cell proliferation and by promoting genomic instability. Expression in normal tissues is nearly undetectable. However, in hematopoietic malignancies and in a variety of solid tumors, increased PIM1 expression has been shown to correlate with the stage of disease. This characteristic suggests it can serve as a useful biomarker for cancer diagnosis and prognosis. Several specific and potent inhibitors of PIM1 's kinase activity have also been shown to induce apoptotic death of cancer cells, to sensitize cancer cells to chemotherapy and to synergize with other anti-tumor agents, thus making it an attractive therapeutic target.

• 出版日期2010-9
• 单位上海交通大学