Abstract CT209: A clinical trial of cResponse, a functional assay for cancer precision medicine
Authors: Salpeter Seth , Bar Vered , Aharon Sara , Torovsky Luba , Zundelevich Adi , Shachar Hamutal , Shapira Hagit , Gavert Nancy , Straussman Ravid , Golan Shay , Rosenbaum Eli , Golan Talia , Berger Raanan , Dotan Zohar , Leibovici Dan , Breuer Shani , Rotenberg Yakir , Zick Aviad , Hubert Ayala , Nechushtan Hovav , Neev Guy 
Published: July 2021

Precision cancer therapy has the potential to revolutionize treatment outcome. While genomic analysis has become central to cancer personalized medicine, recent studies have not shown that it drastically improves patient survival as compared to standard drug selection. Additionally, genomic mutations may suggest several treatment protocols without elucidating which approach will yield the best clinical response. Moreover, for many drugs no genetic predictive biomarkers are available. To advance cancer precision diagnostics, we have developed cResponse, a functional drug sensitivity platform to determine individualized patient treatment regimens. Fresh patient cancer samples are taken by biopsy or resection and sectioned into 300 uM slices which when cultured in the cResponse platform demonstrate similar architecture and tissue proliferation to those found in vivo. We show that cResponse is able to preserve human cancer tissue in 3D together with its microenvironment, including endothelial and immune cells, at a high viability (&gt;90%) with continued cell division for 7 days in over twenty types of solids tumors. Importantly, the high viability of the tissue over an extended period of time allows for a rapid genomic profiling to help prioritize drugs to be tested by cResponse, as well as the capacity to evaluate the effects of slow acting drugs such as targeted therapy. To validate the capacity of the cResponse platform to predict patient response to cancer treatment, forty two patients with different cancer types receiving diverse chemotherapeutic and targeted agents were recruited to the study and their tumors were tested using cResponse prior to initiation of treatment. Cancer types included bladder, pancreatic, lung, colorectal, breast and sarcoma. After five days of treatment ex-vivo, the samples were fixed and designated a viability score (ranging from 0 to 100) based on an algorithm composed of a panel of histological and morphological markers. The cResponse score was compared to the clinical response to treatment of 27 patients for which this data is already available. The results demonstrated that cResponse could predict the patient's response with a specificity of 82% (9/11) and a sensitivity of 93.75% (15/16) when compared to the patient's imaging results. In the future, the integration of this platform in directing anti-cancer treatment may lead to better response rate of cancer patients to therapy.

Citation Format: Seth Salpeter, Vered Bar, Sara Aharon, Luba Torovsky, Adi Zundelevich, Hamutal Shachar, Hagit Shapira, Nancy Gavert, Ravid Straussman, Shay Golan, Eli Rosenbaum, Talia Golan, Raanan Berger, Zohar Dotan, Dan Leibovici, Shani Breuer, Yakir Rotenberg, Aviad Zick, Ayala Hubert, Hovav Nechushtan, Guy Neev. A clinical trial of cResponse, a functional assay for cancer precision medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT209.