Szostak M J, Kyprianou N
Division of Urology, Department of Surgery, University of Maryland Medical Center, Baltimore, MD, USA.
Oncol Rep. 2000 Jul-Aug;7(4):699-706. doi: 10.3892/or.7.4.699.
Current therapy for advanced prostate cancer is hampered by the propensity of the disease to progress from an androgen-dependent state to an androgen-independent state. Current treatment for advanced disease is palliative. Therefore, the therapeutic goal for prostate cancer treatment today is to arrest the disease at an early state when it is still localized to the gland. The standard treatment for clinically localized disease is radical prostatectomy or radiation therapy by way of external beam irradiation or local radioactive seed implants (brachytherapy). In advanced disease, the use of radiation therapy is limited to palliation of pain secondary to bone metastases and for spinal cord compression. Tracking residual disease and predicting outcome is limited to following the level of prostate specific antigen (PSA) production, evaluating for bone or solid organ metastasis, and analyzing their preoperative clinical stage, PSA and Gleason's score. Apoptosis as a molecular process of genetically regulated cell death has a critical endpoint that coincides with the goal of successful treatment of human malignancies. Since in cancer treatment the therapeutic goal is to trigger tumor-selective cell death, activation of the apoptotic pathway in prostatic tumor cells offers attractive and potentially effective therapeutic targets. As our understanding of the vital role of apoptosis in the development and growth of the prostate gland has expanded, numerous genes that encode apoptotic regulators have been identified that are severely impaired in prostate tumors. Human prostate cancer cells undergo apoptosis in response to androgen ablation, chemotherapeutic agents and ionizing irradiation. The expression of apoptotic modulators within individual prostate tumors appears to correlate with the cancer cell's sensitivity to traditional therapeutic modalities, including radiotherapy. No strict correlation between radiation-induced apoptosis and longevity of prostate cancer patients has emerged, possibly because the ability to achieve an initial remission alone does not adequately predict long-term outcome and patient survival. In this review we summarize the current understanding of the effects of radiation therapy on prostatic tumor cells within the context of the therapeutic significance of radiation-induced apoptosis in the effective elimination of androgen independent prostate cancer cells. As we enter a new millenium, identification of distinct molecular markers predictive of therapeutic response of prostatic tumors to radiation therapy may afford alternative prognostic indicators in optimizing our treatment protocols for advanced disease.
晚期前列腺癌的当前治疗受到该疾病从雄激素依赖状态进展为雄激素非依赖状态倾向的阻碍。晚期疾病的当前治疗是姑息性的。因此，当今前列腺癌治疗的目标是在疾病仍局限于腺体的早期阶段阻止其发展。临床局限性疾病的标准治疗方法是根治性前列腺切除术或通过外照射或局部放射性粒子植入（近距离放射治疗）进行放射治疗。在晚期疾病中，放射治疗的使用仅限于缓解骨转移引起的疼痛以及脊髓压迫。追踪残留疾病和预测结果仅限于跟踪前列腺特异性抗原（PSA）的产生水平、评估骨或实体器官转移情况以及分析其术前临床分期、PSA和 Gleason评分。细胞凋亡作为基因调控细胞死亡的分子过程，其关键终点与成功治疗人类恶性肿瘤的目标一致。由于在癌症治疗中，治疗目标是引发肿瘤选择性细胞死亡，因此激活前列腺肿瘤细胞中的凋亡途径提供了有吸引力且可能有效的治疗靶点。随着我们对细胞凋亡在前列腺发育和生长中的重要作用的理解不断扩展，已鉴定出许多编码凋亡调节因子的基因，这些基因在前列腺肿瘤中严重受损。人前列腺癌细胞会因雄激素去除、化疗药物和电离辐射而发生凋亡。单个前列腺肿瘤内凋亡调节因子的表达似乎与癌细胞对包括放疗在内的传统治疗方式的敏感性相关。辐射诱导的凋亡与前列腺癌患者的生存期之间尚未出现严格的相关性，这可能是因为仅实现初始缓解的能力并不能充分预测长期结果和患者生存情况。在本综述中，我们在辐射诱导的凋亡在有效消除雄激素非依赖性前列腺癌细胞中的治疗意义的背景下，总结了目前对放射治疗对前列腺肿瘤细胞影响的理解。随着我们进入新千年，鉴定预测前列腺肿瘤对放射治疗反应的独特分子标志物可能为优化我们的晚期疾病治疗方案提供替代的预后指标。
