Researchers identified two biomarkers that predict whether patients with colorectal carcinoma will respond well to treatment with Erbitux (cetuximab) or the chemotherapy agent 5FU, according to a new study.
These findings were published under the title “Molecular Dissection Of Colorectal Cancer In Pre-Clinical Models Identifies Biomarkers Predicting Sensitivity To EGFR Inhibitors” in the journal Nature Communications.
Colorectal carcinoma manifests in different forms, which is why only a fraction of patients respond appropriately to available therapies. More information is needed to understand the molecular mechanisms underlying the development of this disease and provide suitable treatment for each case.
“Colorectal carcinomas are a very heterogeneous group of cancers, and because of this the effectiveness of the available drugs varies,” Marie-Laure Yaspo, study’s first author, said in a news release. “Although we already know about molecular sub-groups, we do not yet fully understand the causal relationships between those molecular patterns and their response to treatment.”
The OncoTrack consortium is a large biobank of cancer samples collected from patient donors, and was created to facilitate the identification of new biomarkers for colon cancer and the development of novel treatments, bringing together academic research and industry.
Researchers collected samples from 106 patients with colorectal carcinomas in stages 1–4 recruited by the consortium. Samples were then grown in lab culture and in mice to test the anticancer effect of 16 drugs and understand the molecular mechanisms involved in the response to treatment.
The team started by analyzing the genetic profile of the samples, thereby obtaining the “molecular fingerprint” of each tumor. In collaboration with Eli Lilly-Madrid, they then tested how tumors responded to different drugs, correlating their response to their molecular fingerprints. In other words, if a tumor responded to a given drug, researchers would analyze the genetic profile of that tumor to identify molecules that can help predict whether other tumors will be responsive to treatment.
Importantly, the analysis identified two biomarkers that predict whether treatment with Erbitux or the chemotherapy agent 5FU will be effective against colorectal carcinoma.
“Through our analyses we learned a lot about the type of colorectal cancer that responds to these drugs,” Yaspo said. “This means that rather than relying on the mutation status alone, we now have much more information on which to base decisions about treatment.”
“This pre-clinical analysis comparing tumors and their models provided us with the most detailed data on colorectal carcinomas available to date,” the researcher added. “Based on these findings it will be possible to develop diagnostic tools that will provide better predictions of the effectiveness of drugs. This means that in the future it may be possible to treat colorectal cancer patients more individually based on the type of tumor they have.”