Sumiyoshi Takayuki, Akamatsu Shusuke
Dept. of Urology, Kyoto University Graduate School of Medicine.
Gan To Kagaku Ryoho. 2021 Oct;48(10):1203-1208.
With increasing treatment options for metastatic prostate cancer(mPC), there is a growing attention to circulating tumor cells(CTC)and circulating tumor DNA(ctDNA)as minimally invasive biomarkers to facilitate precision medicine. CTC count and ctDNA abundance have been reported to be prognostic factors. In addition, on-treatment changes in these values might also be associated with the treatment response. Androgen receptor gene alterations, including ligand-binding domain mutations, copy number amplification, or structural rearrangements, are identified in most metastatic castration-resistant prostate cancer(mCRPC)and associated with treatment response to androgen receptor pathway inhibitors. Alterations in different DNA damage repair genes, including BRCA2, ATM, CDK12, or mismatch repair genes, are linked to favorable response to targeted therapies such as poly(adenosine diphosphate-ribose)polymerase(PARP)inhibitors or immune checkpoint inhibitors. Overactivation of the PI3K signaling pathway is mainly caused by PTEN loss, and several clinical trials are underway to assess the treatment effect of the targeted therapies such as Akt inhibitors. To disseminate treatment strategies using CTC and ctDNA in clinical practice, we will require prospective biomarker-driven clinical trials, development of novel targeted therapies, and exploration of other molecular characteristics such as epigenome.
随着转移性前列腺癌（mPC）治疗选择的增加，循环肿瘤细胞（CTC）和循环肿瘤DNA（ctDNA）作为促进精准医学的微创生物标志物受到越来越多的关注。据报道，CTC计数和ctDNA丰度是预后因素。此外，这些值在治疗过程中的变化也可能与治疗反应相关。在大多数转移性去势抵抗性前列腺癌（mCRPC）中可检测到雄激素受体基因改变，包括配体结合域突变、拷贝数扩增或结构重排，且这些改变与雄激素受体通路抑制剂的治疗反应相关。不同DNA损伤修复基因的改变，包括BRCA2、ATM、CDK12或错配修复基因，与对聚（腺苷二磷酸核糖）聚合酶（PARP）抑制剂或免疫检查点抑制剂等靶向治疗的良好反应有关。PI3K信号通路的过度激活主要由PTEN缺失引起，目前正在进行多项临床试验以评估Akt抑制剂等靶向治疗的效果。为了在临床实践中推广使用CTC和ctDNA的治疗策略，我们需要开展前瞻性生物标志物驱动的临床试验、开发新型靶向治疗方法，并探索其他分子特征，如表观基因组。
