High flowability monomer resists for thermal nanoimprint lithography

International audienc

Clinical Relevance of KRAS-Mutated Subclones Detected with Picodroplet Digital PCR in Advanced Colorectal Cancer Treated with Anti-EGFR Therapy

International audiencePURPOSE:KRAS mutations are predictive of nonresponse to anti-EGFR therapies in metastatic colorectal cancer (mCRC). However, only 50% of nonmutated patients benefit from them. KRAS-mutated subclonal populations nondetectable by conventional methods have been suggested as the cause of early progression. Molecular analysis technology with high sensitivity and precision is required to test this hypothesis.EXPERIMENTAL DESIGN:From two cohorts of patients with mCRC, 136 KRAS, NRAS, and BRAF wild-type tumors with sufficient tumor material to perform highly sensitive picodroplet digital PCR (dPCR) and 41 KRAS-mutated tumors were selected. All these patients were treated by anti-EGFR therapy. dPCR was used for KRAS or BRAF mutation screening and compared with qPCR. Progression-free survival (PFS) and overall survival (OS) were analyzed according to the KRAS-mutated allele fraction.RESULTS:In addition to the confirmation of the 41 patients with KRAS-mutated tumors, dPCR also identified KRAS mutations in 22 samples considered as KRAS wild-type by qPCR. The fraction of KRAS-mutated allele quantified by dPCR was inversely correlated with anti-EGFR therapy response rate (P < 0.001). In a Cox model, the fraction of KRAS-mutated allele was associated with worse PFS and OS. Patients with less than 1% of mutant KRAS allele have similar PFS and OS than those with wild-type KRAS tumors.CONCLUSIONS:This study suggests that patients with mCRC with KRAS-mutated subclones (at least those with a KRAS-mutated subclones fraction lower or equal to 1%) had a benefit from anti-EGFR therapies

Enrichment and analysis of ctDNA

International audienceColorectal cancer is one of the leading cause of death by cancer worldwide in both men and women. Liquid biopsy belongs nowadays to the landscape of cancer management biological tools. In this chapter, we will describe and discuss the actual, potential and future applications of cfDNA analysis in plasma of patients with colorectal cancer in early or metastatic stage. During the last decade, the development of molecular biology assays like digital PCR or next-generation sequencing made the analysis of cfDNA in plasma possible with an excellent sensitivity and applications like early detection, diagnosis, prognosis, response to treatment, monitoring of an emerging resistance, mapping of the disease molecular landscape or evaluation of the residual disease are now feasible. cfDNA detection has several promising applications in the management of patients with colorectal cancer, but prospective randomised clinical trials are still lacking to make liquid biopsy ready for prime-time