Clonal origin and spread of metastatic prostate cancer

Abstract

Metastatic disease is responsible for the majority of prostate cancer deaths. The standard treatment for metastatic disease is surgical or chemical castration in the form of androgen deprivation therapy. Despite initial success and disease regression, resistance to therapy ultimately develops and the disease transitions to castration resistant prostate cancer, which is uniformly fatal. Thus, developing an understanding of genetic evolution in metastasis and in response to therapy has been a focus of recent studies. Large-scale sequencing studies have provided an expansive catalog of the mutation events that occur in the prostate cancer genome at various stages of disease progression. Smaller-scale studies have interrogated the genomic composition of multiple metastatic sites within individual patients, or have tracked clonal evolution longitudinally in tissues, circulating tumor cells, or circulating tumor DNA. Collectively, these efforts have provided a new conceptual framework for understanding the origin of prostate cancer, as well as the origin and evolution of metastatic disease. In this review, we will highlight these recent insights into the spatiotemporal landscape of genetic evolution of prostate cancer.

Does index tumor predominant location influence prognostic factors in radical prostatectomies?

“…However, although the hypothesis that each metastasis originates from a single tumor cell is generally supported, several studies have supported the existence of polyclonal seeding from an interclonal cooperation between multiple subclones. These latter findings bring insights to find the “true” index lesion by looking on genetic, epigenetic and proteomic alterations ( 5 , 6 ).…”

Electron Microscopic Identification of Distant Metastatic Cell in Human Prostate Cancer in Tissue section

“…Several studies have shown that DNA is shed into the blood stream of advanced metastatic castration resistant prostate cancer (CRPC) and this circulating DNA can be used as a marker (Wyatt et al, 2017) (Ritch andWyatt, 2018) (Annala et al, 2018). CRPC is u)niformly fatal disease (Van Etten and Dehm, 2016). These studies did not identify (or categorize metastatic cell.…”

“…Mutation enables cancer cells to sustain chronic proliferation in invasive and metastatic cells whereas benign prostate and benign prostatic hyperplasia (BPH) do not have that advantage (Hanahan and Weinberg, 2011) (Bryden et al, 2001) (Scholzen and Gerdes, 2000) (Lindboe and Torp, 2002). Metastatic disease is responsible for majority of PC deaths (Van Etten and Dehm, 2016). Metastasis usually occurs in about 10% PC patients indicating metastatic inefficiency (Weiss, 1981).…”

New strategy to distinguish clonal origin of RHCC/MHCC between intrahepatic metastasis and multicentric occurrence

“…Currently, it has approved that multiform clonal origins exist in malignant tumor. Identifying the clonal origin is of great significance for exploring tumor occurrence and evaluating tumor evolution [18][19][20][21][22] . For solidary tumor, there are two types of clonal origin, monoclonal origin and polyclonal origin [23] .…”