Glycoprotein non-metastatic b (GPNMB): A metastatic mediator and emerging therapeutic target in cancer.
Glycoprotein non-metastatic b (GPNMB): A metastatic mediator and emerging therapeutic target in cancer.
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DOI：
10.2147/ott.s44906
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发表时间：
2013
影响因子：
4
通讯作者：
Siegel PM
中科院分区：
文献类型：
--
作者：
Maric G;Rose AA;Annis MG;Siegel PM
由于其高度选择性的抗肿瘤作用，分子靶向治疗在其临床发展和对癌症治疗的影响方面正在迅速发展。然而，许多侵袭性癌症，如三阴性乳腺癌(TNBC)，目前缺乏明确的治疗靶点，可以针对这些药物进行开发。肿瘤相关抗原的识别和抗体药物结合物的产生是癌症治疗领域中一个新兴的研究领域。糖蛋白非转移性b(GPNMB)是近年来发现的一种在包括TNBC在内的多种肿瘤中高表达的基因，且常与转移表型相关。在乳腺癌中，肿瘤上皮细胞中GPNMB的表达与无病生存率和总生存率的降低有关。基于这些发现，格伦巴单抗维多丁(CDX-011)是一种选择性靶向GPNMB的抗体-药物结合物，目前正在对转移性乳腺癌和无法切除的黑色素瘤患者进行临床试验。该综述分别讨论了GPNMB在正常组织和肿瘤组织中的生理和潜在的病理作用，并详细介绍了靶向表达GPNMB的恶性肿瘤的临床进展和挑战。
Molecularly targeted therapies are rapidly growing with respect to their clinical development and impact on cancer treatment due to their highly selective anti-tumor action. However, many aggressive cancers such as triple-negative breast cancer (TNBC) currently lack well-defined therapeutic targets against which such agents can be developed. The identification of tumor-associated antigens and the generation of antibody drug-conjugates represent an emerging area of intense interest and growth in the field of cancer therapeutics. Glycoprotein non-metastatic b (GPNMB) has recently been identified as a gene that is over-expressed in numerous cancers, including TNBC, and often correlates with the metastatic phenotype. In breast cancer, GPNMB expression in the tumor epithelium is associated with a reduction in disease-free and overall survival. Based on these findings, glembatumumab vedotin (CDX-011), an antibody-drug conjugate that selectively targets GPNMB, is currently being investigated in clinical trials for patients with metastatic breast cancer and unresectable melanoma. This review discusses the physiological and potential pathological roles of GPNMB in normal and cancer tissues, respectively, and details the clinical advances and challenges in targeting GPNMB-expressing malignancies.