Affiliation:
1. Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Abstract
As we move into the era of precision medicine, the growing relevance of genetic alterations to prostate cancer (PCa) development and treatment demonstrates the importance of characterizing preclinical models at the genomic level. Our study investigated the genomic characterization of eight PCa cell lines to understand which models are clinically relevant. We designed a custom AmpliSeq DNA gene panel that encompassed key molecular pathways targeting AR signaling, apoptosis, DNA damage repair, and PI3K/AKT/PTEN, in addition to tumor suppressor genes. We examined the relationship between cell line genomic alterations and therapeutic response. In addition, using DepMap’s Celligner tool, we identified which preclinical models are most representative of specific prostate cancer patient populations on cBioPortal. These data will help investigators understand the genetic differences in preclinical models of PCa and determine which ones are relevant for use in their translational research.
Funder
Intramural Research Program of the National Institutes of Health, National Cancer Institute, Bethesda, MD, USA
Reference74 articles.
1. Resistance to second-generation androgen receptor antagonists in prostate cancer;Schmidt;Nat. Rev. Urol.,2021
2. Novel signatures of prostate cancer progression and therapeutic resistance;Wang;Expert. Opin. Ther. Targets,2023
3. Mechanisms of Therapeutic Resistance in Prostate Cancer;Nakazawa;Curr. Oncol. Rep.,2017
4. Chandrasekar, T., Yang, J.C., Gao, A.C., and Evans, C.P. (2015). Targeting molecular resistance in castration-resistant prostate cancer. BMC Med., 13.
5. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: Recommendations of the Prostate Cancer Clinical Trials Working Group;Scher;J. Clin. Oncol.,2008