Autor: |
Luszczak S; Molecular Diagnostics and Therapeutics Group, University College London, London, UK., Kumar C; Molecular Diagnostics and Therapeutics Group, University College London, London, UK., Sathyadevan VK; Molecular Diagnostics and Therapeutics Group, University College London, London, UK., Simpson BS; Molecular Diagnostics and Therapeutics Group, University College London, London, UK., Gately KA; Trinity Translational Medicine Institute, St. James's Hospital Dublin, Dublin 8, Dublin, Ireland., Whitaker HC; Molecular Diagnostics and Therapeutics Group, University College London, London, UK., Heavey S; Molecular Diagnostics and Therapeutics Group, University College London, London, UK. s.heavey@ucl.ac.uk. |
Jazyk: |
angličtina |
Zdroj: |
Signal transduction and targeted therapy [Signal Transduct Target Ther] 2020 Jan 31; Vol. 5 (1), pp. 7. Date of Electronic Publication: 2020 Jan 31. |
DOI: |
10.1038/s41392-020-0109-y |
Abstrakt: |
PIM kinases have been shown to play a role in prostate cancer development and progression, as well as in some of the hallmarks of cancer, especially proliferation and apoptosis. Their upregulation in prostate cancer has been correlated with decreased patient overall survival and therapy resistance. Initial efforts to inhibit PIM with monotherapies have been hampered by compensatory upregulation of other pathways and drug toxicity, and as such, it has been suggested that co-targeting PIM with other treatment approaches may permit lower doses and be a more viable option in the clinic. Here, we present the rationale and basis for co-targeting PIM with inhibitors of PI3K/mTOR/AKT, JAK/STAT, MYC, stemness, and RNA Polymerase I transcription, along with other therapies, including androgen deprivation, radiotherapy, chemotherapy, and immunotherapy. Such combined approaches could potentially be used as neoadjuvant therapies, limiting the development of resistance to treatments or sensitizing cells to other therapeutics. To determine which drugs should be combined with PIM inhibitors for each patient, it will be key to develop companion diagnostics that predict response to each co-targeted option, hopefully providing a personalized medicine pathway for subsets of prostate cancer patients in the future. |
Databáze: |
MEDLINE |
Externí odkaz: |
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