Nelson P S, Gleason T P, Brawer M K
Department of Medical Oncology, University of Washington, Seattle, Seattle 98108, USA.
Eur Urol. 1996;30(2):269-78. doi: 10.1159/000474180.
To evaluate the potential application of chemoprevention strategies in prostatic intraepithelial neoplasia.
Review of relevant literature on chemoprevention with emphasis on prostate cancer and premalignant lesions.
Chemoprevention represents a strategy designed to inhibit or reverse the process of carcinogenesis by administering one or several noncytotoxic chemical compounds. The epidemiology of prostate carcinoma indicates that this cancer is a prime candidate for a strategy aimed at prevention due to the extremely high prevalence rate, rising annual incidence, and long latent interval between the cancer-initiating events and the development of invasive disease. Chemopreventive agents may exert their inhibitory effects at different stages of the multistep carcinogenic process broadly categorized as initiation, promotion, and progression. The synthetic retinoids, polyamine synthesis inhibitors, and antiandrogens are among the compounds shown to have in vitro or in vivo chemopreventive effects in prostate carcinogenesis. A major limitation in the evaluation of such agents in a human prostate cancer is the long duration of clinical trials required to assess the efficacy with an endpoint of cancer development. Premalignant epithelial changes such as prostate intraepithelial neoplasia, or PIN, are highly associated with prostate cancer, and share many molecular features of invasive cancer. If the reversal or inhibition of intraepithelial neoplasia translates to a concomitant reduction in clinically relevant prostate cancer, then the pharmacological modulation of PIN may provide a rapid means to evaluate the effects and benefits of potential chemopreventive agents.
Men with PIN may represent ideal candidates for chemoprevention protocols. The ideal agent and duration of therapy remains to be defined.
评估化学预防策略在前列腺上皮内瘤变中的潜在应用。
回顾有关化学预防的相关文献，重点关注前列腺癌和癌前病变。
化学预防是一种通过给予一种或几种非细胞毒性化合物来抑制或逆转致癌过程的策略。前列腺癌的流行病学表明，由于其极高的患病率、逐年上升的发病率以及致癌起始事件与侵袭性疾病发生之间的较长潜伏期，这种癌症是预防策略的主要候选对象。化学预防剂可能在多步骤致癌过程的不同阶段发挥抑制作用，该过程大致可分为启动、促进和进展阶段。合成视黄酸、多胺合成抑制剂和抗雄激素等化合物已被证明在前列腺癌发生过程中具有体外或体内化学预防作用。在人类前列腺癌中评估此类药物的一个主要限制是，以癌症发生为终点评估疗效需要进行长时间的临床试验。癌前上皮变化，如前列腺上皮内瘤变（PIN），与前列腺癌高度相关，并且具有侵袭性癌症的许多分子特征。如果上皮内瘤变的逆转或抑制转化为临床相关前列腺癌的相应减少，那么PIN的药理调节可能提供一种快速方法来评估潜在化学预防剂的效果和益处。
患有PIN的男性可能是化学预防方案的理想候选者。理想的药物和治疗持续时间仍有待确定。
