The majority of drugs either affect, inhibit, or eliminate gene-encoded proteins. Many are, themselves, proteins. To that end, functional genomics is making important contributions to drug discovery, whether it’s deconvoluting targets or elucidating mechanism of actions. Now, a novel technology, PGA (Patient-derived Gene expression-informed Anticancer drug efficacy), takes an expression-wide approach to determine the efficacy of anticancer drugs for each individual patient.

Researchers at OncoDxRx screened more than 700 clinical and investigational drugs against each patient’s gene expression profile to obtain the most effective drugs. Their study could help to significantly broaden treatment options for patients who are unresponsive to targeted therapy, and could identify previously unknown potential benefits of existing drugs.

This work is published in Onco in the paper, “A Transformative Technology Linking Patient’s mRNA Expression Profile to Anticancer Drug Efficacy.” (https://www.mdpi.com/2673-7523/4/3/12)

“Many drugs can do more than we think,” said OncoDxRx. “We believe that many widely used cancer drugs will also have off-label effects of which we are still unaware. One of the goals of our research is to systematically seek them out without having to wait for such accidental discoveries.”

The researchers first established patient-unique gene expression signature, then used the data to digitally fish out effective drugs with a 5-day turnaround. Most of the drugs are currently used in cancer treatment or are in the clinical approval stage.

Cancer is a prime example of why uncovering a detailed understanding of cellular networks is so important: Different cancers have very different processes going on at the molecular and gene level. Analysis of each patient’s data provided molecular explanations for known phenotypic drug effects and uncovered new aspects of the MoA of human medicines. With the personalized data, OncoDxRx team was able to show, for example, that the patient’s tumor would highly likely to respond to HDAC inhibitors, followed by MEK inhibitors. Unlike the biomarker testing which is solely based on tumor-specific DNA mutations, PGA could also potentially pick up non-tumor signals (i.e., from TME) thus enhancing the treatment of tumors that leverage the immune system.

OncoDxRx is hoping that the results, and PGA in general, will harbor insights into previously undiscovered effects of widely used cancer drugs. Ultimately, a drug repurposing pipeline that can relieve the everlasting drug shortage problem.