Gourdin Theodore, Sonpavde Guru
Medical University of South Carolina, Charleston, SC 29425, USA.
Dana Farber Cancer Institute, Genitourinary Oncology Section, Boston, MA 02215, USA.
Asian J Androl. 2018 May-Jun;20(3):230-237. doi: 10.4103/aja.aja_1_18.
Prostate cancer is characterized by bone metastases and difficulty of objectively measuring disease burden. In this context, cell-free circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) quantitation and genomic profiling afford the ability to noninvasively and serially monitor the tumor. Recent data suggest that ctDNA and CTC quantitation are prognostic for survival. Indeed, CTC enumeration using the CellSearch platform is validated as a prognostic factor and warrants consideration as a stratification factor in randomized trials. Changes in quantities of CTCs using CellSearch also are prognostic and may be employed to detect a signal of activity of new agents. Molecular profiling of both CTCs and ctDNA for androgen receptor (AR) variants has been associated with outcomes in the setting of novel androgen inhibitors. Serial profiling to detect the evolution of new alterations may inform drug development and help develop precision medicine. The costs of these assays and the small quantities in which they are detectable in blood are a limitation, and novel platforms are required to address this challenge. The presence of multiple platforms to assay CTCs and ctDNA also warrants the consideration of a mechanism to allow comparison of data across platforms. Further validation and the continued development and standardization of these promising modalities will facilitate their adoption in the clinic.
前列腺癌的特征是骨转移以及客观测量疾病负担存在困难。在此背景下，游离循环肿瘤DNA（ctDNA）和循环肿瘤细胞（CTC）的定量分析及基因组图谱分析能够实现对肿瘤的无创且连续监测。近期数据表明，ctDNA和CTC定量分析对生存具有预后价值。事实上，使用CellSearch平台进行的CTC计数已被确认为一种预后因素，在随机试验中也有必要作为分层因素加以考虑。使用CellSearch检测到的CTC数量变化同样具有预后价值，可用于检测新药物的活性信号。对CTC和ctDNA进行雄激素受体（AR）变异体的分子图谱分析与新型雄激素抑制剂治疗效果相关。进行连续图谱分析以检测新变异的演变情况，可为药物研发提供信息并助力精准医学的发展。这些检测方法的成本以及在血液中可检测到的量较少是一个限制因素，因此需要新的平台来应对这一挑战。用于检测CTC和ctDNA的多种平台的存在，也有必要考虑建立一种机制，以便能够跨平台比较数据。对这些有前景的检测方法进行进一步验证以及持续开发和标准化，将有助于它们在临床中的应用。
