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Genetic Forecasting May Predict Response to Cetuximab in Colorectal Cancer

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Key Points

  • In 75% of people who initially responded to cetuximab, liquid biopsies picked up changes in the RAS gene before a computed tomography scan was able to show that their colorectal cancer had relapsed.
  • Liquid biopsies also selected 54% of people with colorectal cancer cancer whose tumors already had changes in the RAS gene before they were treated with cetuximab, meaning the drug would have been unlikely to work for them.

Blood tests could predict how long it takes until colorectal cancer becomes resistant to treatment based on the same principle used in forecasting the weather, a new study by Khan et al in Cancer Discovery has found. The liquid biopsies could also predict patients that are unlikely to initially respond to treatment.

Researchers developed a computer model that can track the evolution of cancer from tumor DNA in blood samples when they are taken frequently and at set intervals.

Knowing when treatment is likely to become ineffective could give clinicians more time to prepare for the next step in a patient’s treatment, and to consider offering them alternative therapies or enroll them in a clinical trial.

Researchers at The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust analyzed tumor and blood samples from people with advanced colorectal cancer who took part in the phase II PROSPECT-C trial.

The team combined tumor DNA analysis from frequent liquid biopsies taken at least every 4 weeks with mathematical modelling to track how the genetic make-up of the tumor evolved over time.

Tissue biopsies and blood samples are key tools to help detect changes in tumor DNA, which can signal changes in the way tumors are growing and responding to treatment. When cancer cells contain certain genetic changes, they can be—or evolve to become—resistant to treatment.

Findings

Researchers found that a computer model could predict the estimated waiting time until the tumor would stop responding to the EGFR inhibitor cetuximab (Erbitux). In 75% of people who initially responded to cetuximab, liquid biopsies picked up changes in the RAS gene before a computed tomography scan was able to show that their colorectal cancer had relapsed.

The researchers also looked at the way changes in the RAS gene affect the response and resistance to cetuximab. Liquid biopsies selected 54% of people with colorectal cancer cancer whose tumors already had changes in the RAS gene before they were treated with cetuximab, meaning the drug would have been unlikely to work for them.

David Cunningham, MD, FRCP, FMedSci, Director of the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research, who was chief investigator of the clinical trial associated with the study, said: “Despite tailored selection, we know cetuximab only works for 50% of patients, so it is crucial to identify those who will not respond to this treatment as early as possible. This avoids unnecessary treatment with a drug we know will not work, and means we can consider alternatives at an earlier stage.”

“Tumors shed tiny fragments of DNA into the blood, and these fragments—known as circulating tumour DNA—can be picked up by a…liquid biopsy. Liquid biopsies are quicker, cheaper, and less invasive than taking a sample of body tissue. By analyzing the DNA for genetic alterations, also known as somatic mutations, we can follow the progression of a patient’s tumor over time and predict whether they will respond to a particular treatment.”

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®.


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