期刊
CANCERS
卷 13, 期 14, 页码 -出版社
MDPI
DOI: 10.3390/cancers13143531
关键词
pediatric solid tumors; targeted therapies; precision medicine; personalized medicine; receptor tyrosine kinases; tyrosine kinase inhibitors
类别
Precision oncology offers a more effective treatment option for pediatric solid tumors, particularly those driven by kinase fusions. However, the efficacy of these treatments is limited for tumors without genetic alterations due to the lack of predictive biomarkers.
Simple Summary Children with metastatic or relapsed solid tumors remain in desperate need of better treatment since conventional chemotherapy is often ineffective and can cause long-term complications. Precision oncology offers the possibility of less toxic and more beneficial treatment through the targeting of critical molecular vulnerabilities in tumors. Small molecule inhibitors of receptor tyrosine kinases have shown impressive activity in treating tumors with activating kinase fusions that drive oncogenesis and demonstrate the potential promise of precision oncology. However, in the absence of fusions or activating mutations, the activities of these agents have been more modest and are limited by intrinsic or acquired resistance and the lack of predictive biomarkers. In this manuscript, we track the development of receptor tyrosine kinase inhibitors for treating extracranial pediatric solid tumors and discuss relevant strategies to help optimize the use of these agents. Receptor tyrosine kinases are critical for the growth and proliferation of many different cancers and therefore represent a potential vulnerability that can be therapeutically exploited with small molecule inhibitors. Over forty small molecule inhibitors are currently approved for the treatment of adult solid tumors. Their use has been more limited in pediatric solid tumors, although an increasing number of single-agent and combination studies are now being performed. These agents have been quite successful in certain clinical contexts, such as the treatment of pediatric tumors driven by kinase fusions or activating mutations. By contrast, only modest activity has been observed when inhibitors are used as single agents for solid tumors that do not have genetically defined alterations in the target genes. The absence of predictive biomarkers has limited the wider applicability of these drugs and much work remains to define the appropriate patient population and clinical situation in which receptor tyrosine kinase inhibitors are most beneficial. In this manuscript, we discuss these issues by highlighting past trials and identifying future strategies that may help add precision to the use of these agents for pediatric extracranial solid tumors.
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