Sakellakis Minas, Jacqueline Flores Laura, Ramachandran Sumankalai
Fourth Oncology Department and Comprehensive Clinical Trials Center, Metropolitan Hospital, 18547 Athens, Greece.
Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, University of Texas, Houston, TX 77025, USA.
Exp Ther Med. 2022 May;23(5):351. doi: 10.3892/etm.2022.11278. Epub 2022 Mar 28.
Although prostate cancer is a major cause of cancer-related mortality worldwide, most patients will have a relatively indolent clinical course. Contrary to most other types of cancer, even the diagnosis of locally advanced or metastatic disease is not always lethal. The present review aimed to summarize what is known regarding the underlying mechanisms related to the indolent course of subsets of prostate cancer, at various stages. The data suggested that no specific gene alteration by itself was responsible for carcinogenesis or disease aggressiveness. However, pathway analysis identified genetic aberrations in multiple critical pathways that tend to accumulate over the course of the disease. The progression from indolence into aggressive disease is associated with a complex interplay in which genetic and epigenetic factors are involved. The effect of the immune tumor microenvironment is also very important. Emerging evidence has suggested that the upregulation of pathways related to cellular aging and senescence can identify patients with indolent disease. In addition, a number of tumors enter a long-lasting quiescent state. Further research will determine whether halting tumor evolution is a feasible option, and whether the life of patients can be markedly prolonged by inducing tumor senescence or long-term dormancy.
尽管前列腺癌是全球癌症相关死亡的主要原因，但大多数患者的临床病程相对惰性。与大多数其他类型的癌症不同，即使是局部晚期或转移性疾病的诊断也并非总是致命的。本综述旨在总结关于前列腺癌各阶段惰性病程相关潜在机制的已知情况。数据表明，没有任何一种特定的基因改变本身会导致致癌作用或疾病侵袭性。然而，通路分析确定了多个关键通路中的基因畸变，这些畸变往往会在疾病进程中累积。从惰性状态进展为侵袭性疾病与涉及遗传和表观遗传因素的复杂相互作用有关。免疫肿瘤微环境的作用也非常重要。新出现的证据表明，与细胞衰老相关通路的上调可以识别出惰性疾病患者。此外，许多肿瘤会进入长期静止状态。进一步的研究将确定阻止肿瘤进展是否是一个可行的选择，以及通过诱导肿瘤衰老或长期休眠是否能显著延长患者的生命。
