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CRC Molecular Profiling Moves Field Closer to Individualizing Therapy After Disease Resection

In the ongoing pursuit to tailor treatment to an individual’s specific disease, researchers at Duke University are attempting to identify molecular signatures that subclassify colorectal cancers (CRCs) into clinically relevant subgroups based on gene expression profiling. Although the CRC molecular subgroups are not yet ready to be applied to clinical practice, as is already standard practice in breast cancer, the findings push the field closer to being able to predict which CRC subgroups are likely to respond to specific therapies. (Abstract 339)

 “These subgroups have prognostic implications for recurrence following surgical resection and may help to identify therapies in the adjuvant setting after resection of either primary or metastatic disease,” according to lead study investigator Joshua M. Uronis, PhD, of the Institute for Genome Sciences and Policy at Duke University. “The hope is that in the future we’ll be able to use a model like this to profile patients and more accurately guide drug selection, rather than just blindly choosing drugs to treat patients,” he told the Daily News.

 The Duke investigators analyzed microarray data from 850 patients with predominantly primary CRC and 133 patients with predominantly metastatic CRC to identify general patterns of dysregulated pathway signaling. Computer analysis sifted out six distinct molecular subgroups of CRC.

Recurrence-free survival differed markedly across the six subgroups regardless of whether the analysis was restricted to patients with primary CRC (p = 0.0009) or metastatic CRC (p = 0.046).

Patient-derived CRC explant models developed by the Duke research group are being developed to validate drug sensitivity in vivo, with promising early results already seen.