The following is a summary of “Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma,” published in the June 2023 issue of the Cancer Cell by Lahtinen et al.
Typically, ovarian high-grade serous carcinoma (HGSC) is diagnosed at an advanced stage, with multiple genetically heterogeneous clones already present in the lesions before the initiation of treatment. The researchers integrate clonal composition and topology using whole-genome sequencing data from 510 samples of 148 patients with HGSC in the prospective, longitudinal, multi-region DECIDER study.
Their findings reveal three evolutionary phases with distinct genomic, biochemical, and morphological phenotypes and a significant correlation with treatment response. Analysis of nested pathways reveals two evolutionary trajectories between states. Experiments with five tumor organoids and three PI3K inhibitors support using alpelisib to target malignancies with an amplified PI3K/AKT pathway.
Heterogeneity analysis of samples from numerous anatomical sites reveals that representatives from the place of origin contain 70% more distinct clones than metastatic tumors or ascites. In conclusion, these analysis and visualization methods enable integrative tumor evolution analysis to identify patient subtypes using longitudinal, multiregional cohort data.