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

• Published in: Frontiers in oncology 2023, Vol.13, p.1274163-1274163
• Main Authors: 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
• Format: Report
• Language: English
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2023.1274163

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.