Improving the diagnosis and treatment of Cancer of Unknown Primary using genomic profiling and patient-derived organoids

Atara Posner
PhD Student, Rare Disease Oncogenomics
UMCCR

The current thesis investigated the use of genomic tests to improve diagnosis and treatment for Cancer of Unknown Primary (CUP), a metastatic cancer where the origin of the tumor is unknown making treatment a challenge. Applying a gene-expression tissue of origin test and large gene panel DNA sequencing to 215 CUP patients showed that molecular features could help diagnose the tissue of origin and identify molecular biomarkers for immunotherapy treatment.

The study also compared the benefits and feasibility of whole genome sequencing (WGS) to targeted DNA sequencing in a cohort of 30 CUP patients, identifying specific scenarios where WGS could improve diagnosis and identify missed therapies. Additionally, the study demonstrated the development of CUP patient-derived organoids, which were used for in vitro drug screening of genomic-directed therapies and could serve as avatars of diagnostic entities within CUP. Overall, the study provides insights into how genomic tests can improve the diagnosis and treatment of CUP.