In 1937, President Roosevelt launched the National Cancer Act. Eighty-nine years later, challenges remain despite progress, with 50–80% of patients being unresponsive to treatment and over 600,000 cases of mortality annually in the United States (U.S.) Biomarker tests enable precision medicine but exclude most patients. A disruptive technology is needed to expand precision treatments and benefit every cancer patient. The revolutionary drug-finding technology, PGA (patient-derived gene expression-informed anticancer drug efficacy), has been developed and validated previously, which integrates a patient’s own gene signature to identify the top-ranking drugs that individual patients are most likely to respond to. In this study, we further conducted a benchmarking reality check to evaluate the clinical utility of PGA in real-world settings. To validate PGA LUNG testing results, the framework incorporates three publicly accessible drug utilization datasets for NSCLC: TCGA, MEDLINE, and NCCN guidelines. To enable a comprehensive assessment of PGA LUNG clinical utility, we defined evaluation metrics by capturing drug usage trends in the best clinical practice. Aligned with TCGA treatment landscapes and real-world NSCLC treatment trends in the U.S., the PGA LUNG test could significantly help oncologists by providing them with reliable predictions to choose the most suitable drugs for their patients. PGA LUNG also highlights the potential for off-label cancer drugs to overcome the challenges of ongoing therapy exhaustion and drug resistance. PGA LUNG’s ability to predict drug efficacies/responses for treatment-unresponsive cancer patients with high accuracy provides a critical clinical advantage.

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