Every year, more than two million Americans receive a cancer diagnosis and are offered the promise of precision medicine. Yet for a startling majority, that promise goes unfulfilled. Despite decades of investment in genomic profiling and the regulatory approval of over 200 oncology therapeutics since 2000, real-world data consistently show that only 30 to 50 percent of patients who undergo comprehensive genomic profiling (CGP) carry a guideline-recommended actionable mutation — and of those, fewer than one in five ultimately receives a matched targeted therapy that yields clinical benefit. For the remaining majority, the prevailing answer from conventional biomarker testing is silence. OncoDxRx's Patient-derived Gene expression-informed Anticancer drug efficacy (PGA) assay was conceived precisely to break that silence.

The Invisible Patient: Who Is Left Behind by DNA-Centric Precision Oncology?

The architecture of modern precision oncology is built almost entirely on somatic DNA mutations. This assumption has generated transformative therapies — but it has also created a vast and structurally overlooked patient population for whom the genome offers no actionable instruction. A JCO Precision Oncology study of nearly 4,000 patients with advanced non-small cell lung cancer found that only 32 percent of those receiving CGP had at least one actionable biomarker, and even that applied only to the 20 percent who received comprehensive rather than small-panel testing. Only a minority of patients currently benefit from genomics-guided precision cancer medicine — many tumors lack actionable mutations, and even when targets are identified, inherent or acquired treatment resistance is frequently observed. The majority of cancer patients arrive at the end of their standard-of-care options without a single DNA biomarker guiding their next treatment decision. Current biomarker testing cannot speak to what remains: the functional state of the tumor, the transcriptional programmes actively driving cancer cell survival, and the drug sensitivities that emerge not from mutation but from gene expression.

PGA: Listening to the Tumor Where DNA Falls Silent

The PGA assay operates on a fundamentally different biological premise: that the transcriptome — the ensemble of mRNA molecules actively expressed by a tumor at any given moment — encodes functional identity and drug susceptibility with a fidelity that somatic mutations alone cannot capture. Where DNA catalogues what a tumor can do, RNA reports what it is doing. This distinction is clinically decisive. PGA integrates patient-derived gene expression data, profiled non-invasively from circulating cell-free mRNA (cfmRNA) extracted from a blood draw, into a proprietary computational framework that models the functional activity state of the tumor and predicts anticancer drug efficacy against that specific transcriptomic background. Crucially, PGA does not require the patient to carry a targetable mutation — it requires only that the tumor be expressing genes, which every living tumor inevitably does. This biological universality is the foundation of PGA's clinical scope: every cancer patient is, in principle, a candidate.