Publications by authors named "J Sipola"
Cell phenotype underlies prostate cancer presentation and treatment resistance and can be regulated by epigenomic features. However, the osteotropic tendency of prostate cancer limits access to metastatic tissue, meaning most prior insights into prostate cancer chromatin biology are from preclinical models that do not fully represent disease complexity. Noninvasive chromatin immunoprecipitation of histones in plasma cell-free in humans may enable capture of disparate prostate cancer phenotypes.
View Article and Find Full Text PDFArticle Synopsis
- * In a study involving 264 plasma samples from 63 EOC patients, ctDNA was found in 93% of samples at diagnosis and 100% at disease progression, indicating its effectiveness for monitoring.
- * Positive ctDNA results after treatment correlated with faster disease progression and lower survival rates, and in some cases, ctDNA detected recurrence earlier than traditional methods by an average of 5.9 months.
De novo metastatic prostate cancer is highly aggressive, but the paucity of routinely collected tissue has hindered genomic stratification and precision oncology. Here, we leveraged a rare study of surgical intervention in 43 de novo metastatic prostate cancers to assess somatic genotypes across 607 synchronous primary and metastatic tissue regions plus circulating tumor DNA. Intra-prostate heterogeneity was pervasive and impacted clinically relevant genes, resulting in discordant genotypes between select primary restricted regions and synchronous metastases.
View Article and Find Full Text PDFArticle Synopsis
- * Although ctDNA and tissue biopsies show some similarities in cancer-driving mutations, most of the ctDNA is contributed by only a small number of individual metastases.
- * The research highlights how ctDNA analysis can track changes in genomic drivers of treatment resistance, particularly the role of androgen receptor augmentation, and suggests the potential for liquid biopsies to aid in comprehensive cancer research and monitoring.
Purpose: Cross-resistance renders multiple lines of androgen receptor (AR) signaling inhibitors increasingly futile in metastatic castration-resistant prostate cancer (mCRPC). We sought to determine acquired genomic contributors to cross-resistance.
Experimental Design: We collected 458 serial plasma cell-free DNA samples at baseline and progression timepoints from 202 patients with mCRPC receiving sequential AR signaling inhibitors (abiraterone and enzalutamide) in a randomized phase II clinical trial (NCT02125357).