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Published on: September 19, 2018
Sensitivity Profiles of Human Prostate Cancer Cell Lines to an 80 Kinase Inhibitor Panel
Amy J Burke1, Husnain Ali1, Enda O'Connell2
1Prostate Cancer Institute, National University of Ireland Galway, Galway, Ireland.
Background:
Taxanes and anti-androgen therapies are routinely used for the treatment of metastatic prostate cancer, however the majority of patients eventually develop resistance.
Materials And Methods:
Eighty kinase inhibitors were screened regarding their ability to inhibit cell viability in CWR22, 22Rv1, PC-3 and DU145 prostate cancer cells using automated toxicity assays. Four kinase inhibitors were selected for further investigation.
Results:
No significant difference in sensitivity patterns was found between the androgen receptor wild-type CWR22 and its androgen receptor mutant variant 22Rv1, indicating that androgen receptor mutation did not impact on kinase inhibitor sensitivity in this model. Metastatic PC-3 and DU145 prostate cancer cell lines were less sensitive to kinase inhibitors than the non-metastatic CWR22 and 22Rv1. All four cell lines responded to GSK-3 inhibitor BIO, and MEK inhibitor PD198306. DU145 cells were resistant to p75NTR/TrkA and CHK4 inhibitors, RO-082750 and Ryuvidine.
Conclusion:
Kinase inhibition may be an appropriate strategy for the treatment of prostate cancer.
Insights
Kinase inhibitors show promise for treating metastatic prostate cancer, even when resistance to standard therapies develops. Certain inhibitors effectively reduced cancer cell viability across multiple cell lines.
Area of Science:
- Oncology
- Pharmacology
Background:
- Metastatic prostate cancer treatment commonly involves taxanes and anti-androgen therapies.
- Therapy resistance is a significant challenge in managing metastatic prostate cancer.
Purpose of the Study:
- To screen kinase inhibitors for efficacy against prostate cancer cell lines.
- To identify potential novel therapeutic strategies for prostate cancer.
Main Methods:
- Automated toxicity assays were used to screen 80 kinase inhibitors.
- Four prostate cancer cell lines (CWR22, 22Rv1, PC-3, DU145) were utilized.
Main Results:
- Androgen receptor mutation status did not affect kinase inhibitor sensitivity in CWR22 and 22Rv1 cells.
- Metastatic cell lines (PC-3, DU145) were less sensitive to kinase inhibitors than non-metastatic ones.
- GSK-3 inhibitor BIO and MEK inhibitor PD198306 showed broad efficacy; DU145 cells were resistant to specific inhibitors.
Conclusions:
- Kinase inhibition represents a potential therapeutic strategy for prostate cancer.
- Targeting specific kinases may overcome resistance to current treatments.
