J Cancer
2017; 8(1):140-145.
doi:10.7150/jca.15838 This issueCite
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.
✉ Corresponding author: Luca Mologni, PhD. School of Medicine and Surgery, University of Milan-Bicocca, via Cadore 48, Monza, Italy. Email: luca.mologniit. Tel. +39 0264488148 Or Vera Magistroni, PhD. School of Medicine and Surgery, University of Milan-Bicocca, via Cadore 48, Monza, Italy. Email: vera.magistroniit. Tel. +39 0264488362.More
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
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.
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.