New Study into Benefits of RNA Tumor Profiling Provides Hope for More Effective Cancer Treatment

OmiCure is excited about the future of precision oncology treatment, thanks to a recent study, which is currently awaiting publication, conducted by the National Cancer Institute. While there is still a considerable amount of information needed to enhance this approach, this new publication supports the idea that RNA tumor profiling is headed in the right direction to improve the outcomes for cancer patients.

The National Cancer Institute Brings Precision Oncology Medicine to More Patients

Conducted by Kenneth Aldape, M.D., chief of NCI’s Laboratory of Pathology and Eytan Ruppin, M.D.,Ph.d., head of NCI’s Cancer Data Science Laboratory, this study is finding a way to bring precision oncology treatment to a growing number of patients. Through the WINTHER trial, we started to understand how examining the gene expression in patients’ tumors can drastically change the outcomes by providing more effective, targeted treatment options. This new study further confirms the idea that RNA tumor profiling could  increase the number of patients matched to an effective cancer treatment, and brings a deeper level of understanding of tumor biology.

The role of DNA and mRNA

When a gene is expressed, the DNA is copied into mRNA during a process called transcription. That mRNA is then used to make protein through a process of translation. Researchers and doctors continuously study the relationship between tumor molecular profiles and treatment outcomes, to understand and inform individual patient care. Until the WINTHER trial, most clinical trials focused on precision medicine were based solely on the analysis of alterations in DNA. While this did bring significant advances into the field of precision medicine, there was moderate success in positively impacting the outcomes for patients.

The introduction of RNA tumor profiling seemed to close the gap that existed in finding successful outcomes for patients. Despite its potential,RNA-based testing in a clinic setting has so far been held back, mostly because it can be challenging to­­extract and translate any findings into information that the clinicians can use. Aldape and Rupping’s newest study, describe yet another way to bring this information to the clinicians.

NCI researchers take the next step in putting the translation of that data into action by accurately predicting whether patients respond to previous treatment with targeted therapy or immunotherapy. With these significant advances, researchers can reanalyze data to match an increasing number of patients to the most beneficial treatment option for their tumor profile. Although this breakthrough advance in precision medicine is relatively new, NCI researchers are gradually incorporating this new approach into patient care at the National Institute of Health’sClinical Center. This complements the DNA-based methods that are already in place, bringing the entire cancer community one step closer to more effective treatment plans and better outcomes for patients.

Understanding Relationships Between Genes Helps Oncologists Predict Responses to Targeted Therapy

A growing number of voices and publications surface predicting that RNA tumor profiling is the right direction for precision oncology, bringing hope to doctors, patients, and caregivers that it may possible to identify even more effective cancer treatments and for a larger number of patients. The human genome carries over 20000 genes. When looking at cancer cells, analyzing the relationship between those genes can help influence the prediction of drug therapy outcomes. While some connections between these genes help cells survive, others are harmful.Studies find that the relationships between the patient’s genes affect the potential efficacy of drugs against a patient’s cancer. Understanding those relationships is critical for enabling doctors choose the best individual treatment option for each patient.

Dr. Eytan Ruppin, M.D., Ph.D.

Dr. Ruppin has spent the past several years developing computational tools that take information on gene expression and use it to infer relationships between pairs of genes.

By focusing on genes hit by targeted therapies, Ruppin has been able to analyze publicly available data sets containing molecular data from hundreds of patients and search for interactions across the entire genome. Of course, there’s much more work to be done. With 500 million possible gene-pair combos in the human genome, further advances will take more testing, research, and time. But this new approach certainly has us headed in the right direction.

"Understanding interactions like those could help doctors choose the best treatments for individual patients",
explained Eytan Ruppin, M.D., Ph.D., chief of NCI’s Cancer Data Science Laboratory

With 21 different clinical trials of various targeted therapies, this new approach accurately predicted patients’ responses to treatment in 17 of 21 data sets covering several types of cancer. That’s a significant advancement in the field of precision oncology!And, although Ruppin notes that data isn’t sufficiently accurate all the time, this is a clear signal that precision medicine is a useful resource for cancer patients. This brings hope, and gives researchers and oncologists the drive to push for further testing to learn more about targeted therapy and improve the approach altogether

Comparing the NCI’s New Approach to the WINTHER Trial

One of the best ways to test a new approach is to pit it against an established trial to see if it further enhances the treatment options available to patients. That’s precisely what the NCI did with the WINTHER trial. In the WINTHER trial, clinicians matched patients to treatment based on DNA alterations or RNA levels in the patients’ tumors. But RNA-based therapy was only used for patients with no tumor DNA alterations that could be matched to an effective treatment option. As the first clinical trial to use RNA data to influence treatment decisions, the WINTHER trial provided a significant advance in precision oncology.

The WINTHER trial used an RNA-based approach to match a patient to a treatment based on their tumor’s gene expression. Of 107 patients, 38 responded to treatment in the WINTHER trial.

If Ruppin's new approach guided the WINTHER trial, he predicts that 74 patients could be estimated to respond to RNA tumor profiling and targeted therapy. That’s a whopping 86% of patients. Even considering false-positive tests, Ruppin predicts that oncologists could determine which of 32 FDA-approved targeted cancer therapies would work best for 60% of patients in the trial.

What’s Next?

NCI researchers are still testing this new approach. It’s slowly making its way into use in clinical cancer trials at the NIH Clinical Center. But as NCI leaders continue to consider how to incorporate the approach into patient care effectively, the future is looking very promising. NCI researchers are currently collaborating to plan randomized clinical trials of this new approach. This will address questions about its reliability and solidify the potential benefits RNA tumor profiling has for cancer patients. The National Cancer Institute’s overall goal is to gradually and carefully learn more about the potential benefits of RNA tumor profiling for more effective treatment options through precision oncology.

At OmiCure, we’re excited and hopeful for the future of precision oncology. As we continue to assist the entire cancer community in the quest to find the best possible outcomes for patients, these new publications shine a light on the fact that precision medicine brings us one step closer to better treatment.

Illustration's credit: Adapted from OpenStax

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