September 2023 | George M. Pikler, M.D., Ph.D., FACP

AI Could Help Treat ‘Undiagnosable’ Cancers

Cancer of unknown primary (CUP) encloses a group of heterogeneous tumors, the primary sites for which cannot be identified at the time of diagnosis, despite extensive investigations. CUP accounts for 3–5% of all human malignancies. These patients face obstacles in accessing treatment because many treatments are indicated only for a specific cancer type.

CUP has always posed major challenges both in its diagnosis and management, leading to the hypothesis that it is rather a distinct entity with specific genetic and phenotypic aberrations, considering the regression or dormancy of the primary tumor; the development of early, uncommon systemic metastases; and the resistance to therapy. Multiple case-control and cohort studies have failed to find conclusive risk factors for CUP.

In a recent publication, (1) researchers report the use of artificial intelligence (AI) with the development of OncoNPC, a machine-learning classifier trained on targeted next-generation sequencing (NGS) to categorize cancers that would otherwise defy classification. The study included data from 36,445 tumors across 22 cancer types from three institutions. Patients with these types of ‘undiagnosable’ cancer who were treated in accordance with the AI’s classification had an increased chance of survival compared with those who were not. According to the study authors, OncoNPC can accurately diagnose the source of cancer in more than 40% of patients with CUP, possibly widening their access to effective treatments.

(1) Nat Med 2023 (29), 2057-2067

Erica Cross, PA


Erica is a board certified Physician Assistant. She obtained her Master’s degree in Physician Assistant studies from Our Lady of the Lake College in Baton Rouge, LA. She began practicing in 2011 and has worked clinically in Orthopedics and Dermatology. The majority of her career has been spent in a Dermatology practice where she assisted in Mohs surgery, treating various types of skin cancer. She also teaches in the medical simulation department at the University of South Alabama and enjoys every aspect of medical education.