Fu Weihua, Madan Elena, Yee Marla, Zhang Hongtao
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, USA.
Biochim Biophys Acta. 2012 Apr;1825(2):140-52. doi: 10.1016/j.bbcan.2011.11.003. Epub 2011 Nov 29.
Prostate cancer remains the most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in men in the United States. The current standard of care consists of prostatectomy and radiation therapy, which may often be supplemented with hormonal therapies. Recurrence is common, and many develop metastatic prostate cancer for which chemotherapy is only moderately effective. It is clear that novel therapies are needed for the treatment of the malignant forms of prostate cancer that recur after initial therapies, such as hormone refractory (HRPC) or castration resistant prostate cancer (CRPC). With advances in understanding of the molecular mechanisms of cancer, we have witnessed unprecedented progress in developing new forms of targeted therapy. Several targeted therapeutic agents have been developed and clinically used for the treatment of solid tumors such as breast cancer, non-small cell lung cancer, and renal cancer. Some of these reagents modulate growth factors and/or their receptors, which are abundant in cancer cells. Other reagents target the downstream signal transduction, survival pathways, and angiogenesis pathways that are abnormally activated in transformed cells or metastatic tumors. We will review current developments in this field, focusing specifically on treatments that can be applied to prostate cancers. Finally we will describe aspects of the future direction of the field with respect to discovering biomarkers to aid in identifying responsive prostate cancer patients.
前列腺癌仍然是美国男性中最常被诊断出的恶性肿瘤,也是癌症相关死亡的第二大主要原因。目前的治疗标准包括前列腺切除术和放射治疗,通常还可能辅以激素疗法。复发很常见,许多患者会发展为转移性前列腺癌,而化疗对此仅具有中等疗效。显然,对于初始治疗后复发的恶性前列腺癌形式,如激素难治性前列腺癌(HRPC)或去势抵抗性前列腺癌(CRPC),需要新的治疗方法。随着对癌症分子机制认识的进步,我们见证了新型靶向治疗形式的前所未有的进展。几种靶向治疗药物已被开发并临床用于治疗实体瘤,如乳腺癌、非小细胞肺癌和肾癌。其中一些试剂调节癌细胞中丰富的生长因子和/或其受体。其他试剂靶向在转化细胞或转移性肿瘤中异常激活的下游信号转导、生存途径和血管生成途径。我们将回顾该领域的当前进展,特别关注可应用于前列腺癌的治疗方法。最后,我们将描述该领域未来方向的各个方面,涉及发现生物标志物以帮助识别反应性前列腺癌患者。