IGF-1R可能成为三阴性乳腺癌的治疗靶标

根据癌第四届症治疗发展分子诊断学美国癌症研究学会国际会议上的数据，三阴性乳腺癌患者可能有唯一的可使他们接受更多靶向治疗的生物标志物，其中三阴性乳腺癌是最难治疗的亚型。

三阴性乳腺癌是雌激素受体、孕酮受体和HER2检测皆为阴性的乳腺癌。由于这种生物学特征，这些癌症对内分泌疗法或曲妥珠单抗治疗无响应。

"在其他乳腺癌亚型中，你可以使用这些具有一定疗效的药物。但是，三阴性乳腺癌目前缺乏治疗靶标，而且是用常规的化疗进行治疗"，美国费城托马斯o 杰弗逊大学医院(Thomas Jefferson University Hospital) 病理学副教授Agnieszka K. Witkiewicz医学博士说。

Witkiewicz检查了97位三阴性乳腺癌患者，其中73人是白人，24人是非洲裔美国人。用免疫组织化学技术评估了胰岛素样生长因子1受体（IGF-1R）蛋白质表达，用显色原位杂交技术评估了IGF-1R基因拷贝的数量。

他们发现在25%病例中IGF-1R过度表达。IGF-1R蛋白质过度表达与基因扩增有关联。

此外，这种受体的表达较低与更高的淋巴结转移风险有关，而较高的表达大致与更小的肿瘤尺寸有联系。在55岁以下的患者中间，IGF-1R过度表达与更长的存活期有联系。

由于阻滞IGF-1R已经是一种治疗肉瘤的成功疗法，Witkiewicz提出可能有潜力也在这种乳腺癌亚型中瞄准这种受体。

"眼下，我们知道它的存在而且我们知道这是一个更好的预后标记，" Witkiewicz说。"下一步将了解三阴性乳腺癌患者是否能从瞄准IGF-1R中受益。"（生物谷bioon.com)

ScienceDaily (Sep. 28, 2010) - Patients with triple-negative breast cancer, one of the hardest subtypes to treat, may have a unique biomarker that would enable them to receive more targeted therapy, according to data presented at the Fourth AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

Triple-negative breast cancers are breast cancers that have tested negative for estrogen receptors, progesterone receptors and HER2. Because of this biology, these cancers do not respond to endocrine therapies or trastuzumab.

"In other subsets of breast cancer, you can use these drugs with some success. However, triple-negative breast cancers currently lack therapeutic targets and are managed with conventional chemotherapy," said Agnieszka K. Witkiewicz, M.D., an associate professor of pathology at Thomas Jefferson University Hospital in Philadelphia.

Witkiewicz examined 97 patients with triple-negative breast cancer, of whom 73 were white and 24 were African-American. Insulin-like growth factor 1 receptor (IGF-1R) protein expression was evaluated by immunohistochemistry and IGF-1R gene copy number was assessed by chromogenic in situ hybridization.

They found that IGF-1R was overexpressed in 25 percent of the cases. The IGF-1R protein overexpression correlated with gene amplification.

Moreover, low expression of the receptor was associated with greater risk of lymph node metastasis and high expression showed borderline association with lower tumor size. Among patients younger than 55 years, IGF-1R overexpression was associated with longer survival.

Since IGF-1R blockade has been a successful therapeutic approach in sarcomas, Witkiewicz suggested that there may be potential to target this receptor in this breast cancer subtype as well.

"For now, we know that it is there and we know it is a marker of better prognosis," said Witkiewicz. "The next step is to learn if triple-negative breast cancer patients benefit from targeting IGF-1R."