Abstract 5027: Simplified selective electrochemical detection of ctDNA differentiates between cancer progression and regression

Abstract

Abstract Advanced cancers therapies, including personalized ones, often fail. Rapid evaluation of treatment efficacy is therefore critical to reduce medical and financial side effects and, most importantly, facilitate the implementation of a therapy most appropriate for that individual. Current approaches for evaluating treatment are too slow and expensive to rapidly modify therapy. The previously documented selective affinity of DNA to Au surfaces, albeit cumbersome, unsuitable for point-of-care (PoC) applications and having poor discrimination ability, suggested a solution to this clinically important problem. Methods presented herein potentially solve the problem as first illustrated by a studies of plasma from those with and without cancers. Multiple improvements, most notably optimized buffer conditions dramatically changed and enhanced the difference in adsorption between ctDNA and normal cfDNA drastically improving assay performance. The enhanced sensitivity of this Therascape™ assay was not only able to better detect the difference between healthy and cancer cfDNA but demonstrated potential for the monitoring of cancer treatment efficacy. De-identified clinical samples of the few patients that the Scripps Biorepository and University of Colorado supplied had samples before and after treatment, and were known to have progressed or responded in the interim, were analyzed. This initial group included 6 lymphoma patients and two NSCLC patients (in one case the cfDNA was isolated from urine). One of the patient samples taken before initiating therapy was in the healthy range and considered ineligible for the assay. Ten before and after pairs were then evaluated in a blinded fashion. TheraScape correctly correlated with the change in cancer burden in each pair (10/10 times, p = 0.00016, paired t-test). In some cases the “after” specimen was ~1 month after therapy began. The presentation will include additional patients. The CVs of repeat electrodes were less than 10%, interoperator variability did not increase this. The novel method of detecting cfDNA using disposable electrodes presents a significant advancement in monitoring the efficacy of treatments for advanced cancers, and may be particularly critical for immunotherapy. This approach reduced expenses by 10 to 50 times compared to current reimbursement rates for sequence dependent methods, even more critical is the same day turn around would allow rapid, truly individualized, patient therapy optimization. Citation Format: Matthew Jordan Russo, Kirsten Arnold, Shannon Tunney, Suzin Wright, Floyd Taub, Charles S. Henry. Simplified selective electrochemical detection of ctDNA differentiates between cancer progression and regression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5027.