AUTHOR=Al Assaad Majd , Shin Nara , Sigouros Michael , Manohar Jyothi , Antysheva Zoia , Kotlov Nikita , Kiriy Daria , Nikitina Anastasiia , Kleimenov Mikhail , Tsareva Anastasiya , Makarova Anastasiya , Fomchenkova Victoria , Dubinina Julia , Boyko Alexandra , Almog Nava , Wilkes David , Escalon Joanna G. , Saxena Ashish , Elemento Olivier , Sternberg Cora N. , Nanus David M. , Mosquera Juan Miguel TITLE=Deciphering the origin and therapeutic targets of cancer of unknown primary: a case report that illustrates the power of integrative whole-exome and transcriptome sequencing analysis JOURNAL=Frontiers in Oncology VOLUME=13 YEAR=2024 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1274163 DOI=10.3389/fonc.2023.1274163 ISSN=2234-943X ABSTRACT=

Cancer of unknown primary (CUP) represents a significant diagnostic and therapeutic challenge, being the third to fourth leading cause of cancer death, despite advances in diagnostic tools. This article presents a successful approach using a novel genomic analysis in the evaluation and treatment of a CUP patient, leveraging whole-exome sequencing (WES) and RNA sequencing (RNA-seq). The patient, with a history of multiple primary tumors including urothelial cancer, exhibited a history of rapid progression on empirical chemotherapy. The application of our approach identified a molecular target, characterized the tumor expression profile and the tumor microenvironment, and analyzed the origin of the tumor, leading to a tailored treatment. This resulted in a substantial radiological response across all metastatic sites and the predicted primary site of the tumor. We argue that a comprehensive genomic and molecular profiling approach, like the BostonGene© Tumor Portrait, can provide a more definitive, personalized treatment strategy, overcoming the limitations of current predictive assays. This approach offers a potential solution to an unmet clinical need for a standardized approach in identifying the tumor origin for the effective management of CUP.