|  Gaps in the Field of Lymphatic Research  |  2026–27 Update  |  7
CLINICAL SCIENCE 
RESEARCH: GAPS AND 
NEEDS FOR RARE 
LYMPHATIC DISEASES
• There are big gaps in the collaborative collection  
of data and biospecimens for rare lymphatic and  
vascular anomalies.
• We need natural history studies.
• We need broader, more comprehensive, and 
collaborative registries.
• Gaps in early diagnosis and therefore with delayed 
diagnosis comes morbidity and mortality. 
• We need more non-invasive diagnostic tests and 
biomarkers for lymphatic and vascular anomalies. 
• Drug mechanism studies: how does sirolimus or  
any drug used currently for CLAs work (e.g., 
trametinib, apelesib). How do we assess pharma-
cokinetics response? How do we evaluate drug 
resistance (pathway investigation) with all  
of these drugs?
• Do we need dual therapy, working on both the  
PIK3 and RAS pathways?
• Better evaluation of response (radiologically) and 
standardized outcome measures. 
• Development of validated patient reported outcomes 
and other clinical outcomes.
• Other assessments for genotype that are safer than 
biopsy (i.e.,circulating free DNA).
• Need federal legislation for clinical trials and 
genomic testing.
• Need more pilot studies for novel therapies.
• Need orphan drug designations of medications.
• Need PK analysis for pediatric dosing.
• Need novel methods for drug delivery directly into 
affected tissue and cells to avoid the toxic side effect 
profile of existing and new drugs (with accompanying 
animal models to test these methods).
• Need to be able to target mutant endothelial  
cells and reduce toxic side effects of drugs used  
for treatment. 
• Is trametinib a better treatment for RAS pathway 
driven CLAs than sirolimus? What other MEK- 
inhibitors may be better with less side effects?
• How do mutations in genes that cause CLAs affect 
initial lymphatics and collecting lymphatics?
• Are there therapies besides obvious targeted 
therapies that would be effective at treating CLAs? 
• Can the lymphatic disease be monitored by  
imaging (e.g., FDG-PET, fMRI, or other novel 
techniques)?
• Why do mutations in PIK3CA cause different 
phenotypes?

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