PGA Identifies Effective Drugs for Non-responder Cancer Patients

A team of multidisciplinary researchers at OncoDxRx has developed a proprietary technology dubbed “PGA” (Patient-derived Gene expression-informed Anticancer drug efficacy) that they suggest may help clinicians bring potentially effective drugs to a wider range of cancer patients. The scientists say the tool has already helped to uncover new drug utility across various cancers, which could pave the way for a new wave of highly focused cancer treatments.

The implications of this discovery are significant. PGA not only presents new drugs for therapy but also challenges and expands our understanding of pathway-driven drug responses. Applied broadly to distinct forms of malignancy, OncoDxRx believes that PGA could be used to identify existing drugs that are effective across malignancies and discover new applications that expand the repertoire of treatment strategy for precision oncology.

Targeted and combination therapy has emerged as “a crucial strategy” for combating cancer. This therapeutic strategy effectively harnesses targeted drug’s specificity to fight cancer, often targeting neoantigens produced from genetic mutations. Unfortunately, the approach typically benefits only those with actionable mutation(s) representing only 20-30% of cases.

PGA aims to expand the universe of effective therapies by identifying drugs arising from patients’ own gene expression signature (GES)—and particularly drug repurposing—which until now have remained largely untapped.

Using new in silico computation approaches, PGA predicts drugs that are most likely to work in each individual patient. This approach is vital in developing combination therapy that engage both tumors and the adaptive immune system.

PGA’s dry-lab approach is an easy-to-use computational tool to identify, prioritize, and interpret distinct classes of cancer drugs. The workflow incorporates advanced mapping and analyses to discover effective drugs.

While cataloging all possible drugs matched from GES, the team found that in patients with lung cancer, the implementation of PGA testing correlated with patient survival.

The team also established cancer type-specific biomarkers through their liquid biopsy-focused profiling. These cell-free mRNA transcripts showed great promise for the development of molecular diagnostics and tailored therapies.

PGA is only the beginning. The testing workflow’s scalability means it can be continuously adapted as we make further inroads into understanding and combating cancer.

OncoDxRx’s study provided evidence that cancer type-specific, patient-derived GES can be confirmed in different patient cohorts and used to predict drug response and survival. The company is now applying the tools in the most difficult-to-treat cancers to find the best drugs for therapy development.