Molecular imaging for guiding oncologic prognosis and therapy in esophageal adenocarcinoma.
Molecular imaging for guiding oncologic prognosis and therapy in esophageal adenocarcinoma.
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DOI：
10.3810/hp.2011.04.399
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发表时间：
2011-04
影响因子：
--
通讯作者：
Wang TD
中科院分区：
文献类型：
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作者：
Yentz S;Wang TD
在过去的30年里，食管腺癌的发病率急剧上升。不幸的是，治疗的进展并没有遵循同样的趋势，食管腺癌患者的预后仍然很差，5年生存率仅为15%。与大多数癌症一样，早期检测是改善预后的关键，但由于以下几个原因，这种结果在食管中被证明是困难的：1）患者患有晚期疾病，因为“警报症状”，如吞咽困难发生在晚期，2）常规监测内窥镜检查无法看到高度异型增生（HGD）和早期腺癌（ACA）。目前，建议的监测战略涉及随机活检的收集，这是一种不完善的技术，受到抽样误差的限制，由于需要相当多的时间和费用，很少使用。即使在活检证实的异型增生患者中，仍然缺乏足够的临床管理决策指导。单独的异型增生并不是进展为腺癌风险的完全可靠的生物标志物，因为这种疾病的自然史是非常可变的。显然，需要额外的生物标志物来更好地表征这种疾病，从而提高我们对个体患者进行治疗的能力。随着我们更好地了解导致这种癌症发展的分子变化，需要新的分子生物标志物来进行更个性化的诊断，监测和治疗。目前正在评估针对EGFR、HER 2/neu和VEGF的靶向药物在转移性食管腺癌联合化疗中的作用。随着这些研究的进展，确定个体患者受体状态的可靠方法至关重要。分子成像使用靶向特定细胞表面受体的荧光探针，并有可能评估个体患者的基因表达谱。通过在内窥镜检查期间将荧光探针局部应用于发育不良上皮，可以可视化各种受体，并且可以真实的实时监测对治疗的反应。这项技术可以减轻目前监测方案的局限性，改善癌症检测，并在未来用于真正的个性化治疗。
In the last 30 years, the incidence of esophageal adenocarcinoma has skyrocketed. Sadly, advances in treatment have not followed the same trend, and the prognosis for patients with esophageal adenocarcinoma remains poor with a 5-year survival rate of only 15%. Like most cancers, early detection is the key to improving prognosis, but this outcome has proven difficult in the esophagus for several reasons: 1) patients present with advanced disease because “alarm symptoms” such as dysphagia occur at a late stage, and 2) high-grade dysplasia (HGD) and early adenocarcinoma (ACA) are not visible on routine surveillance endoscopy. Currently, the recommended surveillance strategy involves collection of random biopsies, an imperfect technique that is limited by sampling error and is infrequently used because of the considerable time and cost it requires. Even in patients with biopsy-proven dysplasia, adequate guidance for clinical management decisions is still lacking. Dysplasia alone is not an entirely reliable biomarker for the risk of progression to adenocarcinoma because the natural history of this condition is extremely variable. Clearly, there is a need for additional biomarkers that can better characterize this disease, and thus improve our ability to treat patients on an individual basis. As we better understand the molecular changes that lead to the development of this cancer, new molecular biomarkers are needed to allow for more personalized diagnoses, surveillance and treatment. Targeted agents against EGFR, HER2/neu and VEGF are currently being evaluated for their role in combination chemotherapy for metastatic esophageal adenocarcinoma. As these studies progress, a reliable approach for determining receptor status in individual patients is essential. Molecular imaging uses fluorescent probes that target specific cell surface receptors, and has the potential to evaluate an individual patient’s gene expression profile. By topically applying fluorescent probes to dysplastic epithelium during endoscopy, a variety of receptors can be visualized, and the response to treatment can be monitored in real time. This technique can mitigate the limitations of current surveillance protocols, allow for improved cancer detection, and be used for truly personalized treatment in the future.