人表皮生长因子受体2（HER-2）检验开发市场调研报告

人表皮生长因子受体2（HER-2）检验开发市场调研报告

一、人表皮生长因子受体2（HER-2）市场应用背景

1.人表皮生长因子受体2（HER-2）基本信息

人表皮生长因子受体2 (Human epidermal growth factor receptor 2, HER-2)是表皮生长因子受体(epidermal growth factor receptor, EGFR)家族成员之一，是一种定位于细胞膜的酪氨酸激酶[1]。HER-2是一个位于染色体17q12的原癌基因，编码一个185 kDa的跨膜酪氨酸生长因子受体，该基因的主要作用是控制过度或失控的细胞生长、分化和修复[1]。这种糖蛋白与EGFR家族成员具有广泛的同源性，与其他EGFRs不同，HER-2具有固有的酪氨酸激酶活性，可在没有配体的情况下激活受体介导的信号转导[1]。目前，HER-2在多种肿瘤中均有表达，是肿瘤治疗的关键靶点[2, 3]。HER-2通过胞外-胞内信号传导调节细胞生长、分化以及肿瘤的发生发展[4, 5]。曲妥珠单抗和拉帕替尼是靶向HER-2的两种主要治疗药物[6]。

2.人表皮生长因子受体2（HER-2）临床应用

2.1 HER-2与乳腺癌

乳腺癌分为Luminal A型、Luminal B型、HER-2过表达型（HER-2+）和Basal-like型4种分子亚型[7]。其中， HER-2+的乳腺癌占所有乳腺癌患者的20-30%，是一种高度增殖和侵袭性的乳腺癌亚型，通常与耐药性、较高的脑转移发生率和较差的临床结局相关[8-13]。

2.2 HER-2与胃癌

1986年首次发现HER-2在胃癌中过表达[14]。最新报道的胃癌HER-2阳性率为7.3% ~ 20.2%[14]。近年来，HER-2表达与被证实与胃癌预后之间存在关系。Kurokawa等人的研究评估了1148例接受胃切除术的胃癌患者HER-2表达对预后的影响。他们发现，HER-2表达的差异对胃癌的生存率有明显的影响，所有HER-2阳性患者的生存期均短于HER-2阴性患者，提示HER-2过表达是胃癌患者的不良预后因素[16]。此外，HER-2表达状态与Bormann分型、Lauren分型、肿瘤分化程度、淋巴结状态、静脉侵犯、脉管侵犯密切相[17]。

2.3 HER-2与肺癌

肺癌中HER-2的激活主要通过基因突变(1% ~ 4%)、基因扩增(2% ~ 5%)和蛋白过表达(2% ~ 30%)3种机制发生，且不同机制的预后和预测结果不同[18]。相比之下，选择性更强的新型HER-2酪氨酸激酶抑制剂，在既往接受过治疗的HER-2突变的肺癌患者中显示出很有前景的活性，缓解率分别高达38%和44%[18]。试验表明，在既往接受过一种或多种全身性治疗后疾病进展的HER-2突变晚期非鳞状NSCLC患者中，曲妥珠单抗能够有效缓解肿瘤进展[19]。一些HER-2靶向药物，如T-DXd、来那替尼、阿法替尼、波奇替尼和吡咯替尼，已在晚期肺癌患者中进行了评估，其中一些显示出临床获益[20]。

2.4 HER-2与结直肠癌

约5%的转移性结直肠癌患者存在HER-2扩增，其已被研究为抗表皮生长因子受体(EGFR)治疗耐药的机制之一[21]。在RAS野生型转移性结直肠癌患者中，曲妥珠单抗联合拉帕替尼或帕妥珠单抗的双重HER-2抑制已显示出有前景的初步抗肿瘤疗效[22]。此外，HERACLES-A和DESTINY-CRC01试验等研究表明，HER-2阻断对HER-2扩增的转移性结直肠癌患者有显著的临床获益[21]。

2.6 HER-2与胆道癌

HER-2阻断已被建议在部分胆道癌患者中用于缓解肿瘤的进展[23]。Hiraoko等人的研究表明，HER-2异质性在胆道癌中发生率较高(83%)，且HER-2阳性的肿瘤细胞在浸润较深的区域表达降低，同时伴有去分化现象[24]。总的来说，可以考虑对较大的HER-2阳性胆道癌病例进行HER-2靶向治疗[24]。

3．总结

在肿瘤发生过程中，HER-2参与乳腺癌、胃癌、肺癌、结直肠癌和胆道癌的发生和发展，HER-2靶向治疗广泛应用于多种癌症的治疗。

二、人表皮生长因子受体2（HER-2）市场情况调研

1.全国收费情况

2．证书注册情况

国内厂家注册情况

国外厂家注册情况

三、人表皮生长因子受体2（HER-2）开发建议

HER-2在多种肿瘤的诊断、预后和治疗评估上有重要的研究与应用价值。收费方面，有9省份对于该项目有医保收费信息，价格由165~720不等，属于绝对高值项目。有10家中国企业获得该项目NMPA注册证，4个外国企业获得该项目NMPA注册证（5张注册证）。其中使用荧光原位杂交法检测共8项，免疫组化法检测共2项，测序法共2项，PCR法1项，化学发光免疫分析法1项，酶联免疫吸附法检测的1项。由此荧光原位杂交法为HER-2主流检测方法。

Reference

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