Abstract
Cancer genomics and translational medicine rely on the molecular profiling of patient's tumor obtained during surgery or biopsy. Alternatively, blood is a less invasive source of tumor DNA shed, amongst other ways, as cell-free DNA (cfDNA). Highly-sensitive assays capable to detect cancer genetic events from patient's blood plasma became popularly known as liquid biopsy (LqB). Importantly, retrospective studies including small number of selected patients with metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapy have shown LqB capable to detect the acquired clonal mutations in RAS genes leading to therapy resistance. However, the usefulness of LqB in the real-life clinical monitoring of these patients still lack additional validation on controlled studies. In this context, we designed a prospective LqB clinical trial to monitor newly diagnosed KRAS wild-type (wt) mCRC patients who received a standard FOLFIRI-cetuximab regimen. We used BEAMing technique for evaluate cfDNA mutations in KRAS, NRAS, BRAF, and PIK3CA in twenty-five patients during a 2-y period. A total of 2,178 cfDNA mutation analyses were performed and we observed that: a) continued wt circulating status was correlated with a prolonged response; b) smoldering increases in mutant cfDNA were correlated with acquired resistance; while c) mutation upsurge/explosion anticipated a remarkable clinical deterioration. The current study provides evidences, obtained for the first time in an unbiased and prospective manner, that reinforces the utility of LqB for monitoring mCRC patients.
Highlights
Colorectal cancer (CRC) is the second most common neoplasm in humans, accounting for more than 1.3 million new cases and approximately 700,000 deaths per year [1]
Liquid biopsy (LqB) is a blood exam that is capable of detecting circulating tumor cells (CTCs) and/ or small fragments of cell-free tumor DNA, which are shed into the bloodstream from both primary www.impactjournals.com/oncotarget
The present study summarizes the results of a prospective study of liquid biopsies performed on KRAS wt metastatic CRC (mCRC) patients who were treated with Folinic acid (FOLFIRI)-cetuximab as a frontline treatment
Summary
Colorectal cancer (CRC) is the second most common neoplasm in humans, accounting for more than 1.3 million new cases and approximately 700,000 deaths per year [1]. Treatment with anti-EGFR antibodies prolongs overall survival in RAS wt mCRC patients. These patients progress, at least partially because of the emergence of mutations that occur in genes in the RAS pathway during treatment [2,3,4,5]. Liquid biopsy (LqB) is a blood exam that is capable of detecting circulating tumor cells (CTCs) and/ or small fragments of cell-free tumor DNA (cfDNA), which are shed into the bloodstream from both primary www.impactjournals.com/oncotarget Patient Primary tumor. Liquid biopsy and clinical results Best response.
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