Grundy Megan, Narendran Aru
Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
POETIC Laboratory for Preclinical and Drug Discovery Studies, Division of Pediatric Oncology, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
Front Pediatr. 2022 Aug 10;10:910268. doi: 10.3389/fped.2022.910268. eCollection 2022.
Clinical trials completed in the last two decades have contributed significantly to the improved overall survival of children with cancer. In spite of these advancements, disease relapse still remains a significant cause of death in this patient population. Often, increasing the intensity of current protocols is not feasible because of cumulative toxicity and development of drug resistance. Therefore, the identification and clinical validation of novel targets in high-risk and refractory childhood malignancies are essential to develop effective new generation treatment protocols. A number of recent studies have shown that the hepatocyte growth factor (HGF) and its receptor Mesenchymal epithelial transition factor (c-MET) influence the growth, survival, angiogenesis, and metastasis of cancer cells. Therefore, the c-MET receptor tyrosine kinase and HGF have been identified as potential targets for cancer therapeutics and recent years have seen a race to synthesize molecules to block their expression and function. In this review we aim to summarize the literature that explores the potential and biological rationale for targeting the HGF/c-MET pathway in common and high-risk pediatric solid tumors. We also discuss selected recent and ongoing clinical trials with these agents in relapsed pediatric tumors that may provide applicable future treatments for these patients.
过去二十年完成的临床试验对提高癌症患儿的总体生存率做出了重大贡献。尽管有这些进展，但疾病复发仍然是该患者群体死亡的一个重要原因。通常，由于累积毒性和耐药性的产生，增加当前方案的强度并不可行。因此，在高危和难治性儿童恶性肿瘤中识别和临床验证新靶点对于制定有效的新一代治疗方案至关重要。最近的一些研究表明，肝细胞生长因子（HGF）及其受体间充质上皮转化因子（c-MET）会影响癌细胞的生长、存活、血管生成和转移。因此，c-MET受体酪氨酸激酶和HGF已被确定为癌症治疗的潜在靶点，近年来人们竞相合成分子以阻断它们的表达和功能。在这篇综述中，我们旨在总结探索在常见和高危儿科实体瘤中靶向HGF/c-MET通路的潜力和生物学原理的文献。我们还讨论了最近和正在进行的使用这些药物治疗复发儿科肿瘤患者的临床试验，这些试验可能为这些患者提供适用的未来治疗方法。
