Liquid Biopsies Identify Molecular Alterations Driving Drug Resistance in Nearly 80% of Patients With Gastrointestinal Cancers


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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.

—Ryan Corcoran, MD, PhD
This study shows very clearly how liquid biopsy can change the practice of oncology in the coming years.

—Jean-Charles Soria, MD, PhD

Liquid biopsy technologies are increasingly being used to detect genetic mutations in tumors, giving clinicians the opportunity to see in real time how a patient’s cancer may or may not be responding to treatment. In a study presented recently at the 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Munich, Ryan Corcoran, MD, PhD, presented results from a study looking at how gastrointestinal cancers develop resistance to targeted therapies.1 

Dr. Corcoran is Translational Research Director of the Center for Gastrointestinal Cancers at Massachusetts General Hospital Cancer Center in Boston. The annual symposium is hosted by the European Organisation for Research and Treatment of Cancer (EORTC), National Cancer Institute (NCI), and American Association for Cancer Research (AACR).

Study Background

Dr. Corcoran and colleagues at Massachusetts General Hospital used liquid biopsies to analyze circulating tumor DNA for mutations occurring during therapy leading to drug resistance. “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,” said 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.

Key Findings

“In 31 patients [22 with colorectal cancer, 7 with biliary cancer, and 2 with gastroesophageal cancer], 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.

Ryan Corcoran, MD, PhD

Ryan Corcoran, MD, PhD

Jean-Charles Soria, MD, PhD

Jean-Charles Soria, MD, PhD

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.”

‘Patient-Friendly Approach’

Chair of the Scientific Committee for the Symposium, Jean-Charles Soria, MD, PhD, of the Institut Gustave Roussy, told Symposium attendees, “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.”

Dr. Soria commented, “This study shows very clearly how liquid biopsy can change the practice of oncology in the coming years.” ■

Disclosure: For full disclosures of the study presenters, view the abstracts available at http://www.ecco-org.eu/ENA.

Reference

1. Parikh A, Kwak E, Goyal L, et al: A systematic liquid biopsy program identifies novel and heterogeneous mechanisms of acquired resistance in gastrointestinal (GI) cancer patients. 2016 EORTC-NCI-AACR Symposium. Abstract 4LBA. Presented December 1, 2016.



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