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Pursuing Precision: Receptor Tyrosine Kinase Inhibitors for Treatment of Pediatric Solid Tumors
Andrew J Bellantoni1, Lars M Wagner1
1Division of Pediatric Hematology/Oncology, Duke University, Durham, NC 27710, USA.
Abstract:
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.
Insights
Small molecule inhibitors targeting receptor tyrosine kinases show promise for pediatric solid tumors, especially those with specific genetic alterations. Further research is needed to identify optimal patient populations and treatment strategies.
Area of Science:
- Oncology
- Pharmacology
Background:
- Receptor tyrosine kinases (RTKs) are crucial for cancer cell growth and proliferation.
- Numerous small molecule RTK inhibitors are approved for adult cancers, with increasing investigation in pediatric solid tumors.
Purpose of the Study:
- To review the efficacy and limitations of RTK inhibitors in pediatric solid tumors.
- To identify future strategies for precise application of these inhibitors in pediatric extracranial solid tumors.
Main Methods:
- Review of past clinical trials involving RTK inhibitors in pediatric solid tumors.
- Discussion of current challenges, including the absence of predictive biomarkers.
- Identification of future research directions and therapeutic strategies.
Main Results:
- RTK inhibitors demonstrate success in pediatric tumors with specific kinase fusions or mutations.
- Limited efficacy observed when used as single agents in tumors lacking targetable genetic alterations.
- Wider applicability of RTK inhibitors is hindered by the lack of predictive biomarkers.
Conclusions:
- RTK inhibitors hold therapeutic potential for pediatric solid tumors, particularly those with defined genetic drivers.
- Development of predictive biomarkers is essential for optimizing patient selection and treatment outcomes.
- Future strategies should focus on enhancing the precision of RTK inhibitor use in pediatric extracranial solid tumors.
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