Biomarker Development

The NTAP Biomarker Development Initiative aims to identify and validate biomarkers that are predictive of how plexiform neurofibromas (pNFs) will behave in patients with neurofibromatosis type 1 (NF1).

NF1 patients typically have multiple pNFs that arise over their lifetime, but there is currently no means to predict whether a given tumor will remain stable or cause significant morbidity. In many cases, pNFs grow to substantial volume over time and, depending on their location, cause serious neurological symptoms and disfigurement. Others will not change significantly. A small percentage of pNFs will undergo malignant conversion, transitioning into sarcomas that are often fatal.

This heterogeneity creates challenges in clinical development of novel treatments in multiple ways:

• Without a means to differentiate pNFs that will progress from those that will not, mixed populations of tumors must be evaluated collectively. Consequently, assessing the efficacy of a given treatment is problematic as the effect of treatments can be masked.

• There is a growing body of data that suggests a critical period may exist early in life, during which transient treatment of emerging pNFs may result in prolonged control. To take advantage of this window of opportunity, a mechanism is required to identify which tumors are most likely to respond to benefit from treatment.

The NTAP Biomarker Development Initiative was developed to address these needs by identifying molecular, imaging, or other markers that correlate with pNF behavior.

Working with InnoCentive, an open-source innovation organization that manages prize competitions, NTAP held an idea challenge to identify strategies for the development of reliable biomarkers for pNF. Prizes were awarded to the following ideas:

• Serum exosomal RNA signatures
• Potential metabolic biomarkers for pNF growth using systems biology approaches
• Serum human telomerase reverse transcriptase messenger RNA predictive of pNF growth
• Serum microRNAs: Potential biomarkers for pNF growth
• Imaging: Properties of a stable isotope tracer 13C
• Abnormally hyperactive c-kit pathway detection in NF1 patients to determine the risk of tumor growth