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RON receptor tyrosine kinase in pancreatic ductal adenocarcinoma: Pathogenic mechanism in malignancy and pharmaceutical target for therapy.
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer ( IF 11.2 ) Pub Date : 2020-03-29 , DOI: 10.1016/j.bbcan.2020.188360
Hang-Ping Yao 1 , Rachel Hudson 2 , Ming-Hai Wang 3
Affiliation  

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with poor prognosis and high mortality. Molecular aberrations associated with PDAC pathogenesis and progression have been extensively investigated. Nevertheless, these findings have not been translated into clinical practice. Lack of therapeutics for PDAC treatment is another challenge. Recent application of molecularly targeted and immunoregulatory therapies appears to be disappointing. Thus, discovery of new targets and therapeutics is urgently needed to combat this malignant disease. The RON receptor tyrosine kinase is a tumorigenic determinant in PDAC malignancy, which provides the rationale to target RON for PDAC treatment. In this review, we summarize the latest evidence of RON in PDAC pathogenesis and the development of anti-RON antibody-drug conjugates for potential PDAC therapy. The finding that anti-RON antibody-drug conjugates show efficacy in preclinical animal models highlights the potential of this novel class of anti-cancer biotherapeutics in future clinical trials.

中文翻译:

胰腺导管腺癌中RON受体酪氨酸激酶:恶性肿瘤的发病机制和治疗的药物靶点。

胰腺导管腺癌(PDAC)是预后差,死亡率高的最具侵袭性的癌症之一。与PDAC发病机制和进展相关的分子畸变已得到广泛研究。但是,这些发现尚未转化为临床实践。缺乏用于PDAC治疗的疗法是另一个挑战。分子靶向和免疫调节疗法的最新应用似乎令人失望。因此,迫切需要发现新的靶标和疗法来对抗这种恶性疾病。RON受体酪氨酸激酶是PDAC恶性肿瘤的致癌因素,可为RON靶向PDAC治疗提供依据。在这篇评论中 我们总结了RON在PDAC发病机理中的最新证据以及用于潜在PDAC治疗的抗RON抗体-药物偶联物的发展。抗RON抗体-药物偶联物在临床前动物模型中显示功效的发现凸显了这种新型的抗癌生物治疗药物在未来临床试验中的潜力。
更新日期:2020-04-20
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