RNA-Based Liquid Biopsy Strategy Enables Early Detection of Multiple Cancers

Scientists have discovered and validated tumor-specific, orphan non-coding RNAs (oncRNAs), as well as artificial intelligence (AI) profiling of the oncRNAs to accurately detect cancers of diverse tissue origins. This paves the way for the development of blood tests for the early detection and monitoring of residual disease of many commonly seen cancers.

Exai Bio (Palo Alto, CA, USA) conducted a large study program encompassing more than 10,000 samples (7,942 cancer and 3,021 normal samples) from three large independent cancer cohorts that validated a large class of novel oncRNAs and the utility of AI-based oncRNA profiling for predicting cancer tissue-of-origin. Exai Bio’s technology is based on its unique, proprietary repertoire of oncRNAs, which are an abundant class of small non-coding RNA sequences that are actively secreted only by cancer cells and not normal tissues. As such, oncRNAs can provide a robust disease signal with high sensitivity, low background and, as a result, high specificity, giving the Exai Bio oncRNA platform several advantages over currently employed mutational or epigenomic analyses of circulating tumor-derived DNA.

Image: Next gen liquid biopsy offers insight into cancer and disease biology from standard, non-invasive blood samples (Photo courtesy of Pexels)

Exai Bio first identified a large class of distinct oncRNAs that were significantly present in six key cancer types, using samples from The Cancer Genome Atlas (TCGA). These six cancers (breast, colorectal, gastric, kidney, liver, and lung) represent the majority of cancer mortality worldwide. Next, the oncRNAs from this library were independently validated in two unique IndivuType cohorts, containing 2,245 and 1,252 cancer samples, respectively, and over half of oncRNAs in the library were validated in at least one of the IndivuType cohorts. Finally, Exai Bio developed AI algorithms in the TCGA cohort for predicting the tissue-of-origin of a cancer sample by analyzing its oncRNA profile. The algorithm was validated and had high accuracy (>91%) in each IndivuType cohort, showing that cancer tissues-of-origin are identifiable based on oncRNA profiles alone.

These results demonstrate that oncRNAs are a unique and generalizable feature of cancers that may be applied to improve the care of cancer patients. Exai Bio is focused on early cancer detection for multiple types of cancer, including the 28 cancer types explored in the TCGA cohort, for which it has identified a proprietary library of more than 250,000 novel oncRNAs. The Exai program aims to build on the current data to translate these findings into a liquid biopsy test with broad utility for early detection of cancer and monitoring of minimal residual disease.

“We’re proud of the scientific rigor we are applying to the development and validation of an RNA-based liquid biopsy approach for early cancer detection,” said Patrick Arensdorf, Chief Executive Officer, Exai Bio. “The evidence reported today demonstrates that Exai Bio’s oncRNA platform is biologically valid, clinically oriented and highly accurate in its ability to predict cancer tissue-of-origin. These results build upon our initial discoveries of tumor-specific oncRNAs in neoadjuvant breast cancer patients and validate the presence of further specific oncRNAs across multiple tumor types. We look forward to translating these findings and advancing the development of our RNA-based liquid biopsy diagnostics platform for early cancer detection and minimal disease monitoring.”

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