Liquid biopsy-based assays to monitor residual disease in cancer.

Tumor Biology
Session Type and Session Title: 
General Poster Session, Tumor Biology
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 11096)
Gangwu Mei, Dragan Sebisanovic, Alain Mir, Zulfiqar Gulzar, James D. Brooks, Stefanie S. Jeffrey, AmirAli Talasaz; Guardant Health Inc., Redwood City, CA; Department of Medicine at Stanford University, Stanford, CA; Stanford University, Stanford, CA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: One of the main challenges in cancer management is monitoring the non-organ-confined disease post metastasis. Recently analysis of circulating tumor nucleic acids has generated a new paradigm for monitoring the progression and molecular pathology of the residual disease through a non-invasive test. Methods: We have developed a new sequencing workflow, which increases the sensitivity and specificity of detecting and quantifying rare tumor-derived nucleic acids among healthy fragments by at least ten-fold. Unlike conventional sequencing library preparation protocols, the majority of extracted circulating DNA fragments are hybridized to sequencing flow cells with minimal modifications. The sequencing data are processed using our proprietary bioinformatics pipelines to search for rare genetic abnormalities within the heterogeneous circulating fragments. Results: To study the performance of our technology, we first evaluated its sensitivity in analytical samples. We spiked varying amounts of LNCaP cancer cell line gDNA into a background of normal gDNA and were able to successfully detect somatic mutations down to 0.1% sensitivity. Subsequently, we investigated the correlation of circulating DNA and tumor gDNA in human xenograft models in mice. In seven different mice models of two different human tumors, we found very strong correlation between somatic mutations detected in all pairs of tumor gDNA and mouse blood cfDNA. After preclinical studies, we initiated a pilot study on human samples across different cancer types. We found more than 90% correlation between tumor mutations in stage IIIb CRC cancer patients and the mutations detected in their circulation (n=7). In a pilot study in prostate cancer patients (n=3), we detected chromosomal abnormalities in multi locations in circulating DNA genome in both advanced and post-relapse stages of the disease. Conclusions: The present work indicates the potential of using circulating nucleic acids to facilitate the integration of real-time molecular pathology into routine cancer care. Our assay will be used to identify residual disease after neoadjuvant chemotherapy and/or surgery, but may also identify a subset of patients who may benefit from alternative therapies.