Employing PGA to Optimize Treatment Selection
OncoDxRx’s PGA test provides access – the ability to find a way around. The one-of-a-kind technology can “re-measure the geometry of the tumor with regard to access to more therapeutic options”.
- (1888PressRelease) February 29, 2024 - Treatments for cancer patients generally follow standard clinical protocols that have the highest response rates or survival rates on average, but each patient presents a unique etiology. A new paradigm is emerging that offers oncologists the opportunity to predict how cancers in the body might respond to specific drugs or their combinations, before patients receive chemotherapy, opening new avenues for personalized therapy with optimal likelihood of success.
OncoDxRx has invented a laboratory technique for generating functional genetic profiles as patient-unique fingerprints to select the most effective regimens from roughly 700 existing anticancer drugs. The company claims this approach is more powerful than DNA-based biomarker testing offered at most centers.
At the individual level, responders are 100% responsive and non-responders are 0% responsive. What patients are looking for is to know, to the best of their knowledge, where they fit into the response expectations,” says OncoDxRx.
The exclusive technology, called PGA (Patient-derived Gene expression-informed Anticancer drug efficacy), predicts drug efficacies and is gaining popularity in the treatment of a variety of cancer patient non-responders.
In addition, the team has compiled a large database of human cancer studies that use the PGA protocol in breast, lung, pancreatic cancers. Using PGA in clinical decision-making, they report a significant increase in clinical response and improved progression-free survival and overall survival.
Genetic abnormalities that lead to cancer result in molecular anomalies that could serve as diagnostic, prognostic, and predictive biomarkers for the disease. Identifying these biomarkers in different tumorigenic pathways makes it possible for clinicians to select the most appropriate therapy for each patient.
When talking of breakthroughs—those technologies that more closely approximate genetic activities are closest to the biological behavior of a cell.
Heterogeneity of cellular architecture in tumors in vivo suggests that the over-activation of specific cancer genes and pathways, in particular, those hyperactive ones, determines how tumor’s drug response would be.
PGA technology seeks to mimic or recreate the patient tumor’s key gene expression patterning. It’s not a perfect reproduction, but it does benefit the patients and improve outcomes clinically.
The problem with tumor xenograft-derived organoids that are propagated and grown into 3D cultures is that they are for the most part, not representative of the actual state of affairs in human tissue. Most significantly, these 3D small aggregates are non-permeable to certain drugs, such as combination therapy, large molecule drugs like therapeutic antibodies or antibody-drug conjugates. As these technologies grow in the cancer field, they may not be predictive.
“Most of our patients come to us at fairly advanced stages. Very often they have liver metastasis or extensive lymphadenopathy. We get a biopsy of that. At this stage, they do become somewhat more resistant. We often feel that since they share the truncal mutation and may have acquired new mutations, if we can find activity in those distant sites, it often characterizes the population as a whole—both primary and metastatic.” OncoDxRx notes.
OncoDxRx’s team explored cell-free mRNA (cfmRNA) expression features that enable cancer cells to stay alive and outsmart the immune system. “These can often be measured in the blood or in tissue culture media. The signatures correlate with drug responses. There is a continuum from the state of a cell gaining a survival advantage, utilizing that survival advantage to remain alive to ultimately propagating and metastasizing. They use those same survival advantages to resist chemotherapy and other targeted therapies.”
“cfmRNA studies may for the first time give us a handle on the tumor phenotype from a drop of blood. We’re extremely excited by the opportunity of applying that in the clinical setting.” The company says.
OncoDxRx’s team has compiled laboratory analyses of cancer patients into a comprehensive proprietary database. The database enables the prediction of which drugs are likely to benefit an individual patient based on his/her cfmRNA signature, with a high degree of accuracy.
Despite robust predictive advantage, OncoDxRx laments that PGA technologies have been underestimated in clinical practice and decried in editorials.
“They continue to suggest PGA test needs to prove it save lives. We have never seen a clinical trial where a genomic platform has been forced to show it saves lives,” OncoDxRx says. “What we prove is the performance characteristics of the test within the standards.”
“Once you use this technology, it’s very hard to go back to clinical oncology as it is practiced.”
OncoDxRx believes guideline-driven medicine is increasingly on a collision course with precision medicine. “We better get on the right side of that,” says the company, “because what we’re seeing is increasing standardization of therapies while patients are clamoring for individualized care.”
“We need to be humble in our scientific pursuits so that we allow this extraordinary biological complexity, redundancy, and promiscuity of events to teach us. In our work, we can get the answer—doctors and patients have to provide the question.” OncoDxRx explains.
OncoDxRx hopes PGA testing platform in combination with its exclusive database could be the key to achieving personalized care so that cancer patients are treated based on the latest research optimized for their specific genetic makeup and not just what has been approved for a narrow, generalized indication.
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