J Cancer 2017; 8(1):140-145. doi:10.7150/jca.15838 This issue Cite

Short Research Communication

The Novel PIM1 Inhibitor NMS-P645 Reverses PIM1-Dependent Effects on TMPRSS2/ERG Positive Prostate Cancer Cells And Shows Anti-Proliferative Activity in Combination with PI3K Inhibition

Luca Mologni1✉*, Vera Magistroni1✉*, Francesco Casuscelli2, Marisa Montemartini2, Carlo Gambacorti-Passerini1,3

1. School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy;
2. Nerviano Medical Sciences srl, Nerviano, Milan, Italy;
3. Hematology and Clinical Research Unit, San Gerardo Hospital, Monza, Italy.
* These authors contributed equally to the work.

Citation:
Mologni L, Magistroni V, Casuscelli F, Montemartini M, Gambacorti-Passerini C. The Novel PIM1 Inhibitor NMS-P645 Reverses PIM1-Dependent Effects on TMPRSS2/ERG Positive Prostate Cancer Cells And Shows Anti-Proliferative Activity in Combination with PI3K Inhibition. J Cancer 2017; 8(1):140-145. doi:10.7150/jca.15838. https://www.jcancer.org/v08p0140.htm
Other styles

File import instruction

Abstract

PIM1 is over-expressed in multiple tumors, including prostate cancer (PCa). PIM1 upregulation is mediated by direct binding of the ERG transcription factor to its promoter. About 50% of PCa cases are characterized by the presence of the TMPRSS2/ERG fusion, leading to ERG over-expression and thus to PIM1 transcriptional activation. PIM kinases are considered as weak oncogenes, but when combined with additional genetic alterations can induce strong transforming effects. Here we show anti-proliferative activity of the newly described PIM1 inhibitor NMS-P645 in combination with the PI3K inhibitor GDC-0941 in TMPRSS2/ERG positive and negative PCa cells. Treatment with NMS-P645 alone can reverse PIM1-mediated pro-survival signals in prostate cells, such as activation of STAT3 through Tyr705 phosphorylation and resistance to taxane-based treatments, but does not exert a strong anti-tumoral effect. However, the simultaneous treatment with NMS-P645 and GDC-0941 induces a significant anti-proliferative response in PCa cells. These results support the use of combination strategies with PIM and PI3K inhibitors as effective treatment for PCa cases.

Keywords: Prostate cancer, PIM1, PI3K, kinase, inhibitor.


Citation styles

APA
Mologni, L., Magistroni, V., Casuscelli, F., Montemartini, M., Gambacorti-Passerini, C. (2017). The Novel PIM1 Inhibitor NMS-P645 Reverses PIM1-Dependent Effects on TMPRSS2/ERG Positive Prostate Cancer Cells And Shows Anti-Proliferative Activity in Combination with PI3K Inhibition. Journal of Cancer, 8(1), 140-145. https://doi.org/10.7150/jca.15838.

ACS
Mologni, L.; Magistroni, V.; Casuscelli, F.; Montemartini, M.; Gambacorti-Passerini, C. The Novel PIM1 Inhibitor NMS-P645 Reverses PIM1-Dependent Effects on TMPRSS2/ERG Positive Prostate Cancer Cells And Shows Anti-Proliferative Activity in Combination with PI3K Inhibition. J. Cancer 2017, 8 (1), 140-145. DOI: 10.7150/jca.15838.

NLM
Mologni L, Magistroni V, Casuscelli F, Montemartini M, Gambacorti-Passerini C. The Novel PIM1 Inhibitor NMS-P645 Reverses PIM1-Dependent Effects on TMPRSS2/ERG Positive Prostate Cancer Cells And Shows Anti-Proliferative Activity in Combination with PI3K Inhibition. J Cancer 2017; 8(1):140-145. doi:10.7150/jca.15838. https://www.jcancer.org/v08p0140.htm

CSE
Mologni L, Magistroni V, Casuscelli F, Montemartini M, Gambacorti-Passerini C. 2017. The Novel PIM1 Inhibitor NMS-P645 Reverses PIM1-Dependent Effects on TMPRSS2/ERG Positive Prostate Cancer Cells And Shows Anti-Proliferative Activity in Combination with PI3K Inhibition. J Cancer. 8(1):140-145.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
Popup Image