Researchers Outline Ongoing Potential of ctDNA Analysis in GEA

Unlike the success seen in other cancer types, biomarker-driven treatment advances in gastroesophageal adenocarcinoma (GEA) have been hindered by its genomic heterogeneity. A significant proportion of patients also develop resistant subclones through selective pressure, resulting in disease progression.

A recently published paper is taking a look at the current role and future potential of using circulating tumor DNA (ctDNA) analysis in gastroesophageal adenocarcinoma (GEA), the third-leading cause of cancer death and a need for improved survival.

Unlike the success seen in other cancer types, biomarker-driven treatment advances in GEA have been hindered by its genomic heterogeneity. A significant proportion of patients also develop resistant subclones through selective pressure, resulting in disease progression.

“The rapidly evolving field of blood-based molecular approaches, among which is ctDNA, is ushering in a new era for GEA oncology as multiple applications throughout different disease stages are showing promising results and some have potential transformative value,” commented the researchers, writing in Future Medicine. “MRD detection, molecular selection, treatment monitoring and clonal evolution study appear the most compelling.”

For example, through molecular profiling, ctDNA analysis can be used to measure the plasmatic levels of various biomarkers in order to predict how a patient will respond to treatment and if they will likely relapse following surgery, which in turn can better improve patient selection for treatment.

In one phase 2 study of pembrolizumab used in patients with GEA, researchers showed that ctDNA analysis was effective at determining patients who would likely respond to the treatment by identifying microsatellite instability.

“In parallel, ctDNA may serve as a biomarker for real-time monitoring of treatment efficacy because its levels have been shown to correlate with changes in tumor burden after the administration of effective treatments,” explained the researchers. “Of note, serial blood-based genotyping may lead to the identification of acquired resistance as well as patients’ prognostication, therefore assisting in the selection of later-line treatments. The detection of MRD after potentially curative interventions may allow for the identification of patients at increased risk of relapse and for whom adjuvant therapy may be of greatest value.”

In addition to predicting and tracking response to treatment, ctDNA may also be leveraged to track resistance to treatment among these patients. Several published studies have shown that ctDNA analysis detected mechanisms of resistance, such as HER2 and MET amplification, as well as PI3KCA, NF1, and KRAS mutations.

Reference

Salati M, Venetis K, Fassan M, et al. ctDNA analysis in the personalized clinical management of gastroesophageal adenocarcinoma: turning hope into reality. Future Oncol. Published online August 18, 2021. doi:10.2217/fon-2021-0228.