Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response: Beyond the Abstract
A new study by Nickerson et al. published in the journal Oncogene examined the genomic sequences of 25 bladder cancer cell lines to look at the mutations, copy number alterations and gene expression to correlate them with drug responses.
The authors identified mutations affecting protein function in 76 cancer related genes that mirrored mutations identified in the TCGA dataset. They also identified alterations in several signaling pathways including the PI3K/mTOR pathway, SYNE1–SYNE2 altered in 60% of lines and BRCA DNA repair altered in 44% of cell lines.
The investigators generated a signature based on altered pathways in cell lines and correlated it with each cell line’s sensitivity to Cisplatin. The same signature was then used this information to build a predictive model for Cisplatin-response in patients treated with chemotherapy from the TCGA dataset. Kaplan–Meier survival analysis showed significant difference among patients treated with platinum-based drugs between those predicted to be sensitive and those predicted to be resistant (P = 0.05, log-rank test).
This pharmacogenomics analysis reveals the importance of understanding the genetic architecture of existing bladder cancer cell line models and is a successful example of how this knowledge can be applied to predict response to chemotherapy in patients.
Written by: Bishoy Faltas, MD
References:
Nickerson ML, Witte N, Im KM, Turan S, Owens C, Misner K, Tsang SX, Cai Z, Wu S, Dean M, Costello JC, Theodorescu D. Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response. Oncogene. 2016 Jun 6. doi: 10.1038/onc.2016.172. [Epub ahead of print]