WEBINAR ABSTRACT: PTEN gene loss occurs frequently in castration-resistant prostate cancer (CRPC) and may drive progression through activation of the PI3K/AKT pathway. Here, we developed a novel CTC-based assay to determine PTEN status and examined the correlation between PTEN status in CTCs and matched tumour tissue samples. PTEN gene status in CTCs was evaluated on an enrichment-free platform (Epic Sciences) by fluorescence in situ hybridisation (FISH). PTEN status in archival and fresh tumour tissue was evaluated by FISH and immunohistochemistry. Peripheral blood was collected from 76 patients. Matched archival and fresh cancer tissue was available for 48 patients. PTEN gene status detected in CTCs was concordant with PTEN status in matched fresh tissues and archival tissue in 32 of 38 patients (84%) and 24 of 39 patients (62%), respectively. CTC counts were prognostic (continuous, P ¼ 0.001). PTEN loss in CTCs associated with worse survival in univariate analysis (HR 2.05; 95% CI 1.17–3.62; P ¼ 0.01) and with high lactate dehydrogenase (LDH) in metastatic CRPC patients. Our results illustrate the potential use of CTCs as a non-invasive, real-time liquid biopsy to determine PTEN gene status. The prognostic and predictive value of PTEN in CTCs warrants investigation in CRPC clinical trials of PI3K/AKT-targeted therapies.
WEBINAR ABSTRACT: Spatial heterogeneity of tumors has been identified within and between metastatic lesions and can be visualized with targeted PET imaging, biopsy IHC and microdissected-targeted NGS. Tissue biopsies can underestimate clonal and phenotypic differences between metastatic sites, and lack of single cell characterization can homogenize intra-tumoral heterogeneity.
At Epic Sciences, we have developed a platform to characterize single circulating tumor cells (CTCs) for morphologic, protein and genomic targets at the single cell level and have applied the platform to thousands of samples from metastatic cancer patients. In this webinar we present data on the impact of morphology, protein chemistry and genomics of single CTCs in the context of contemporary unmet clinical needs in mCRPC. The impact of this clinical data suggests employment of a rational development of combination therapies to combat disease heterogeneity.