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PIM kinase inhibition:co-targeted therapeutic approaches in prostate cancer

Signal Transduction and Targeted Therapy 2020年第1期5卷 2430-2439页

作者： Sabina Luszczak Christopher Kumar vignesh krishna sathyadevan Benjamin S.Simpson Kathy A.Gately Hayley C.Whitaker Susan Heavey Molecular Diagnostics and Therapeutics Group University College LondonLondonUK Trinity Translational Medicine Institute St.James’s Hospital DublinDublin 8DublinIreland

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 *** upregulation in prostate cancer has been correlated with decreased patient overall survival and therapy *** 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 ***,we present the rationale and basis for cotargeting 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 *** combined approaches could potentially be used as neoadjuvant therapies,limiting the development of resistance to treatments or sensitizing cells to other *** 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.

关键词： targeted doses viable

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