Researchers have developed a new preclinical platform using patient-derived organoids (PDOs) and xenografts (PDX) to test treatments for pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC). They created 11 “mini-tumors” in the lab that closely mimic the structure, genetics, and biomarkers of the original patient tumors. These models remained stable for over a year, making them ideal for large-scale drug testing.
The study identified potential new treatments beyond standard chemotherapy. Most tumors were sensitive to paclitaxel and SN38 but resistant to cisplatin, while PI3Kα inhibitors, particularly CYH33, showed strong anti-tumor activity. Sensitivity to CYH33 was linked to specific genetic markers like CCND1 amplification.
Researchers also addressed the common KRAS G12D mutation, which often resists single-drug treatments. A combination of a KRAS G12D inhibitor (MRTX1133) with a G9a protein degrader (G9D-4) significantly increased cancer cell death by activating pro-apoptotic pathways. This approach highlights the potential of using tumoroids for precision oncology, guiding tailored treatments, combination therapies, and predictive biomarkers for patients with PDAC and BTC.