[分子诊断和靶向治疗——“吠叫的狗会咬人”:来自美国临床肿瘤学会第42届年会上的报告,亚特兰大,2006]。

A Rody, S Loibl, M Kaufmann
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引用次数: 1

摘要

本届asco会议强化了近年来从经验治疗概念转向量身定制和个性化诊断和治疗的趋势。然而,个体治疗的基础是特定的分子诊断,这可以反映在乳腺癌的激素受体,HER-1, HER-2和拓扑异构酶iα的分析中。所有这些标志物不仅能够预测疾病的进程,而且还可以预测特定治疗方法的成功。曲妥珠单抗是HER-2阳性乳腺癌的标准治疗,无论是辅助治疗还是姑息治疗。但新的治疗药物,如拉帕替尼,在治疗HER-2阳性乳腺癌方面很有希望,即使曲妥珠单抗失败。否则,它可能是另一种选择,但需要等待足够的临床结果。吉非替尼对egfr相关信号转导通路的靶向失活,无论是单独使用还是与内分泌治疗联合使用,都没有显示出实质性的改善。然而,即使分子数据表明ER阳性和PR阴性乳腺癌患者可能是这样一个群体,也必须确定可能从这种治疗中受益的适当亚组。随着对骨转移生物学知识的不断增加,新的治疗方案应运而生,如denosumab,一种人源化的RANK配体单克隆抗体。两项辅助细胞毒性治疗试验显示紫杉烷类药物可改善淋巴结阳性乳腺癌的预后,应按顺序给予治疗。两项临床试验(IES, ARNO)证明,在使用他莫昔芬治疗2 - 3年后改用芳香化酶抑制剂对绝经后患者的内分泌治疗有好处,这可能会证明生存获益。总之,似乎很明显,新的靶向治疗方案是有效的,并将在不久的将来为乳腺癌患者的治疗设定新的标准。卵巢癌的报告重点是在卡铂和紫杉醇作为卵巢癌主要治疗的标准疗法的基础上添加第三种细胞毒性药物。介绍了贝伐单抗治疗原发性和复发性卵巢癌的新数据。然而,这还不是一种适用于所有患者的标准治疗方法,需要在大型、多中心、随机试验中进一步研究。淋巴切除术作为子宫内膜癌主要治疗的一部分似乎至少对晚期疾病或高风险I期肿瘤患者有益。子宫肉瘤的辅助治疗尚未得到很好的研究和明确。一项为期12年的试验表明,对总体生存有好处,但必须谨慎解释。今年,来自德国的有趣的捐款也越来越多,这些捐款也受到了国际关注。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Molecular diagnostic and targeted therapy--"Barking dogs are going to bite": presentations from the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta 2006].

This years ASCO-meeting reinforced the trend of the recent years to get off from empirical treatment concepts to tailored and individualized diagnostics and therapy. However, the basis for an individual therapy is a specific molecular diagnostic which can be reflected in the analysis of hormonal receptor, HER-1, HER-2 and topoisomerase IIalpha in breast cancer. All these markers are not only able to prognosticate the course of disease but they also can predict the success of specific treatment approaches. Trastuzumab is standard therapy in HER-2 positive breast cancer both in the adjuvant and palliative setting. But new therapeutic agents, as e. g. lapatinib, are promising in the treatment of HER-2 positive breast cancer even if trastuzumab is failing. Otherwise it might possibly be an alternative option but adequate clinical results have to be awaited. The targeted inactivation of EGFR-related signal transduction pathways by e. g. gefitinib did not show a substantial improvement neither as a single agent nor in combination with endocrine treatment. However, the appropriate subgroup which might benefit from this therapy has to be defined even if molecular data suggest that patients with ER positive and PR negative breast cancer might be such a group. The increasing knowledge in terms of the biology of bone metastasis led to the development of new treatment options as e. g. denosumab, a humanized monoclonal antibody for RANK ligand. Two adjuvant cytotoxic treatment trials revealed that taxanes improve the prognosis of node positive breast cancer and should be administered sequentially. The advantage of switching to an aromatase inhibitor after two to three years of tamoxifen in endocrine treatment of postmenopausal patients is proved by two clinical trials (IES, ARNO) which could demonstrate a survival benefit. In conclusion it seems to be evident that new targeted therapy options are effective and will set new standards for the treatment of breast cancer patients in the near future. The presentation for the ovarian cancer focused on the addition of a third cytotoxic agent to carboplatin and paclitaxel as the standard therapy for the primary treatment of ovarian cancer. New data of Bevacizumab in the treatment of primary and recurrent ovarian cancer were presented. However, this is not yet a standard treatment for all patients and needs further investigations within large, multicentre, randomised trials. The lymphonodectomy as part of the primary therapy of the endometrial cancer seems to be a benefit at least in patients with advanced disease or high risk stage I tumours. The adjuvant therapy of uterine sarcomas is still not yet very well investigated and clear. A trial which recruited 12 years demonstrated a benefit in overall survival which has to be interpreted with caution. In this year again there have been registered an increasing number of interesting contributions from Germany, which also received international attention.

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