Personalized Drug Screening and Risk Assessment in Patient-Derived Gastroenteropancreatic Neuroendocrine Neoplasms

Area of Science:

• Oncology
• Translational Medicine
• Pharmacology

Background:

• Precision medicine has advanced oncology care but is underutilized in metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs).
• There is a critical need for novel therapeutic strategies in GEP-NENs.

Purpose of the Study:

• To establish and validate a standardized platform for personalized drug screening and risk assessment in GEP-NENs.
• To evaluate individual tumor responses to a range of therapeutic agents.

Main Methods:

• Utilized patient-derived GEP-NEN primary cultures (n=23) from metastatic tumors.
• Performed systematic drug testing on 27 agents, including signaling inhibitors, DNA damage response inhibitors, and chemotherapeutics.
• Assessed cell viability, signaling pathways via Automated Western blotting, and tumor composition via immunohistochemistry.

Main Results:

• Demonstrated significant group effects and individualized drug responsiveness/resistance.
• Identified distinct drug response patterns between pancreatic NETs (pNETs) and small intestinal NETs (siNETs).
• Observed differential responses between GEP-NETs and GEP-NEC.

Conclusions:

• Provided novel efficacy data for various therapies in patient-derived GEP-NEN cultures.
• Established a standardized platform for personalized drug screening and risk assessment in GEP-NENs.
• The platform enables prediction of individual tumor treatment response for this orphan disease.