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| Status |
Public on May 31, 2023 |
| Title |
Patient-derived tumor xenograft study with CDK4/6 inhibitor plus AKT inhibitor for management of metastatic castrate resistant prostate cancer |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
We applied DNA content flow cytometry to a series of prostate cancer (PC) patient derived tumor xenografts (PDTXs). We interrogated purified sorted tumor fractions from each sample with whole genome copy number variant (CNV) analyses. These identified a variety of somatic genomic lesions targeting genes and cellular pathways in PC. Of significant interest are lesions that may affect responses to therapies. Guided by the genomic alterations in these models and interrelated mechanisms between androgen signaling axis, the cell cycle, and AKT pathway, we identified and investigated the combination of CDK4/6 inhibitors with AKT inhibitors as a potential therapy for patients with mCRPC. Using 3-D spheroid drug assays followed by in vivo experiments in three unique PDTX models, these preclinical results highlight the potential use of CDK4/6 inhibitor with AKT inhibitors for the treatment of mCRPC who have intact retinoblastoma pathway, thereby, providing the experimental data support and rationale for future clinical investigation
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| Overall design |
We applied DNA content based flow sorting to isolate the nuclei of clonal populations from prostate tumor patient derived tumor xenografts (PDTXs). We coupled this strategy with oligonucleotide array CGH (aCGH) thereby obtaining high definition genomic profiles of clonal populations from each tumor. Response to CDK4/6 and AKT inhibition was assesed with organoid models derived from the PDTXs.
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| Contributor(s) |
Kase A, Gleba J, Miller JL, Miller E, Petit J, Zhou Y, Barrett MT, Parent EE, Cai H, Knight J, Orme J, Reynolds J, Durham WF, Metz TM, Meurice N, Edenfield B, Demirer AA, Bilgili A, Hickman PG, Pawlush ML, Wickland D, Tan W, Copland III JA |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Apr 24, 2023 |
| Last update date |
Jun 02, 2023 |
| Contact name |
Michael Thomas Barrett |
| E-mail(s) |
barrett.michael@mayo.edu
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| Phone |
480-301-6736
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| Organization name |
Mayo Clinic Arizona
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| Department |
Molecular Pharmacology and Experimental Therapeutics
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| Street address |
13400 East Shea Boulevard
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| City |
Scottsdale |
| State/province |
AZ |
| ZIP/Postal code |
85259 |
| Country |
USA |
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| Platforms (1) |
| GPL19387 |
Agilent-021850 SurePrint G3 Human CGH Microarray (Probe Name version) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA961092 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE230411_RAW.tar |
131.0 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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