Halozyme Therapeutics, San Diego, CA 94121, USA.
Anticancer Res. 2012 Apr;32(4):1203-12.
The tumor microenvironment is an emerging source of novel therapeutic targets in cancer. The glycosaminoglycan hyaluronan (HA) accumulates in 20-30% of tumors and is often associated with poor prognosis.
We developed a digitized, semiquantitative scoring system for tumor-associated HA content, then grouped tumors (from animal models or patients) according to the degree of HA accumulation (HA+1,2,3). The antitumor response to HA-depletion by pegylated PH20 hyaluronidase (PEGPH20) was then characterized as a function of HA accumulation.
Semiquantitative grouping of tumors demonstrated that HA accumulation predicts the response of tumors in animal models to PEGPH20. Prospective analysis of HA content was used to predict response to PEGPH20 of squamous cell-type explants from patients with non-small cell lung cancer in nude mice.
Measurement of HA is a viable biomarker approach for predicting antitumor response in animal models to the HA-depleting agent, PEGPH20.
肿瘤微环境是癌症中新兴的治疗靶点来源。糖胺聚糖透明质酸（HA）在 20-30%的肿瘤中积累，并且通常与预后不良相关。
我们开发了一种用于肿瘤相关 HA 含量的数字化、半定量评分系统，然后根据 HA 积累程度（HA+1、2、3）对肿瘤（来自动物模型或患者）进行分组。然后，根据 HA 消耗对 PEGPH20 聚乙二醇化 PH20 透明质酸酶的抗肿瘤反应进行了特征描述。
肿瘤的半定量分组表明，HA 积累可预测动物模型中 PEGPH20 的抗肿瘤反应。前瞻性分析 HA 含量用于预测 PEGPH20 对裸鼠中非小细胞肺癌患者鳞状细胞型外植体的反应。
HA 的测量是一种可行的生物标志物方法，可预测动物模型中 HA 耗竭剂 PEGPH20 的抗肿瘤反应。
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