Ziv will trace the evolution of pancreatic NETs to a higher grade and more aggressive forms using techniques used to study evolutionary biology.
What problem/questions will researchers try to answer?
Tumor grade remains the most important prognostic variable driving patient outcomes but little is known about how tumor grade changes over time and in response to treatment. Ziv will try to determine if higher grade tumors evolve from lower-grade tumors over time or arise independently and if certain treatments drive tumors to a higher grade.
Why is this important?
Understanding how aggressive tumors arise can inform one of the most pressing dilemmas in current pancreatic NET clinical management including treatment sequencing, the role of surgical debulking and locoregional therapy and surveillance.
What will researchers do?
Analyses of whole-exome and targeted deep sequencing of specimens from multiple time points will be performed to reconstruct tumor cell histories to identify and study why certain tumor cells become more aggressive.
How might this improve the treatment of NETs?
If higher grade tumors can be identified, these tumors can potentially be targeted and eradicated earlier in the course of the disease.
What is the next step?
Data generated by this study will provide the community with information about how and when aggressive tumor cells of pancreatic NETs arise, which can then be used to discover new biomarkers of disease aggressiveness and to test treatment sequencing strategies and inform new therapeutic strategies.