Recent VHIO study reveals that tumor cell sensitivity and resistance to therapy with cetuximab in colorectal cancer can be detected by measuring pEGFR levels in plasma.
Combined use of 3D cell culture and quantitative proteomics to study the response of tumor cells to cetuximab in vitro.
Barcelona, October 30, 2014.– Research led by the Vall d’Hebron Institute of Oncology (VHIO) has established a new, practical, non-invasive method for monitoring treatment with cetuximab in patients with colorectal cancer (CRC). The study, recently published in the journal Clinical Cancer Research, shows a correlation between levels of pEGFR in blood and response to treatment with the drug cetuximab. It seems that the activated form of EGFR (pEGFR) is secreted in response to anti-EGFR therapy. This discovery means it will be possible to monitor what is happening to the tumor and associated metastases during treatment through simple blood tests.
Headed by Josep Villanueva, Principal Investigator of the Vall d´Hebron Institute of Oncology´s (VHIO) Tumor Biomarkers Group, this novel study used three-dimensional (3D) cell culture to enable the researchers to accurately detect the in vitro response of tumor cells to cetuximab, one of the most commonly used drugs in colorectal cancer. This innovative model facilitated the study of how the secreted proteins changed with quantitative proteomics and represents one of the very first projects in proteomics to have led to the discovery of a candidate response biomarker which can be easily measured in blood.
The analysis of the secretome, that is, all the proteins secreted by a cell, by quantitative proteomics presented surprising results. Villanueva’s group found that when tumor cells responded to cetuximab, pEGFR (the activated form of the receptor and the target of this drug) was secreted, and that pEGFR levels correlated with the sensitivity and resistance of the colorectal cancer tumor cells both in vitro and in the plasma of patients receiving cetuximab.
This research has been carried out in collaboration with the Vall d´Hebron University Hospital´s Medical Oncology Department led by Josep Tabernero, who is also both Director of the VHIO and Director of its Clinical Research Program. Thanks to such partnership and connectivity, results at laboratory level were validated in patients, bringing these findings closer to the clinic.
The result of this latest VHIO-led discovery is therefore that measuring pEGFR levels in plasma can immediately reveal whether the treatment is working or not. The researchers validated the in vitro results with plasma samples from CRC patients treated with cetuximab. “The results indicate that we will be able to monitor patients’ response to cetuximab in a non-invasive test by measuring the concentration of pEGFR in their plasma”, summarises Villanueva.
The study had a clear and simple objective: to seek non-invasive and easy-to-measure molecular biomarkers for targeted anti-EGFR therapies. “There is a critical call in oncology to identify markers that indicate whether treatments are effective at the molecular level. This strategy will provide us with a response via a simple blood test”, he explains. If adopted as a biomarker, pEGFR could be used to monitor treatment and track treatment response without the need for repeat CT scans, currently the standard test for monitoring tumor size, which would obviously be less invasive for the patient. “Our preliminary results show great promise. What we have to do now is validate our findings in an extended number of patients”, he concludes.
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For more information please contact: Amanda Wren, Director of Communication, Vall d´Hebron Institute of Oncology (VHIO), Tel.:+34 695207886, Email:awren@vhio.net.
