Potential roles for the PIM1 kinase in human cancer - a molecular and therapeutic appraisal.
In vitro experiments have shown the PIM1 kinase to have diverse biological roles in cell survival, proliferation and differentiation. In humans, PIM1 is often expressed in both normal and transformed cells. The PIM1 kinase is a true oncogene implicated in early transformation and tumour progression in haematopoietic malignancies and prostate carcinomas. It is associated with aggressive subgroups of lymphoma, is a marker of poor prognosis in prostate carcinomas and has been suggested to have a role in hormone insensitivity of prostate malignancies. PIM1 has a possible role in other carcinomas with 6p21 genomic alterations. On one hand, PIM1 (due to its role in malignancy) appears to be a promising target for drug development programmes but, on the other hand, the complexity of its molecular structure has posed challenges in the development of PIM1 inhibitors. In this review we discuss PIM1 expression in human tissues (including some new data from our laboratory), its role in human malignancies, as well as the possibilities and challenges in the development of target therapy for PIM1.
Shah
Nilesh
N
Oncology Research Institute, National University of Singapore, Singapore.
Pang
Brendan
B
Yeoh
Khay-Guan
KG
Thorn
Shannon
S
Chen
Chien Shing
CS
Lilly
Michael B
MB
Salto-Tellez
Manuel
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D051573:Proto-Oncogene Proteins c-pim-1