EORTC-NCI-AACR 2016: Liquid Biopsies Identify Molecular Alterations Driving GI Cancer Drug Resistance in Nearly 80% of Patients
Ryan Corcoran, MD, PhD, Translational Research Director of the Center for Gastrointestinal Cancers at Massachusetts General Hospital (MGH) Cancer Center, described to attendees of the 2016 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics the results of a program at MGH focused on uncovering how gastrointestinal (GI) cancers develop resistance to targeted therapies (Abstract 4LBA).
“To understand GI cancers develop resistance to targeted therapies, we employed a systematic ‘liquid biopsy’ program within the GI cancer center at MGH, by which blood was collected at the time that a patient’s disease stopped responding to treatment and the disease started to progress. Circulating tumor DNA was analyzed by next-generation sequencing to identify mutations that emerged during therapy to drive resistance to treatment,” explained Dr. Corcoran.
“Circulating tumor DNA is shed by tumor cells throughout the body into the bloodstream and can be isolated from a routine blood draw. Since tumor cells residing in different metastatic tumor lesions in the same patient can often evolve distinct mechanisms of drug resistance, ‘liquid biopsy’ analysis of circulating tumor DNA can frequently identify the simultaneous presence of multiple resistance alterations that would be missed by a single-lesion tumor biopsy,” he continued.
Findings
“In 31 patients, this liquid biopsy program identified a molecular alteration driving resistance in nearly 80% of patients, and half of these patients were found to have multiple alterations detectable in the blood. In patients in whom biopsies of the tumor had also been taken at the time that their disease started to progress, liquid biopsy identified additional alterations 62% of the time. Systematic liquid biopsy also led to the discovery of several novel mechanisms of resistance, which can help guide the development of therapeutic strategies to overcome resistance. Overall, these data show how routine clinical implementation of liquid biopsy at the time of disease progression on targeted therapy can effectively identify important mechanisms of resistance and may offer certain advantages relative to tumor biopsies,” said Dr. Corcoran.
He concluded, “One of the biggest advantages of liquid biopsies is that they can be performed from a routine blood draw, sparing patients the necessity of undergoing costly and invasive tumor biopsies, which can also pose some procedural risks for patients. Furthermore, liquid biopsies may better capture ‘tumor heterogeneity’, or the evolution of distinct resistance mechanisms in different tumor cells in independent metastases in the same patient, which might be missed by a needle biopsy of a single tumor lesion.”
Chair of the Scientific Committee for the Symposium, Jean Charles Soria, MD, PhD, of the Institut Gustave Roussy, told the Symposium, “Liquid biopsies are a patient-friendly approach to obtaining critical insight into the intrinsic tumor biology in any given patient. In this case, they have allowed rapid and robust identification of the mechanism of acquired resistance that can help clinicians to select further therapies for the patient.”
“This study shows very clearly how liquid biopsy can change the practice of oncology in the coming years.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
