Liquid biopsy to identify resistance to GI cancer therapy

Parikh AR, Leshchiner I, Elagina L et al. Liquid vs tissue biopsy for detecting acquired resistance and tumour heterogeneity in gastrointestinal cancers. Nature Medicine 2019;25(9):1415–1421.

Tumour heterogeneity and the development of resistant subclones can lead to resistance to therapy. Liquid biopsy (sampling blood plasma to obtain circulating tumour DNA) may be able to capture this acquired resistance more effectively than solid tumour biopsy. Forty-two patients with partial response to targeted therapy underwent liquid biopsy. Twenty-three of these patients had a matched tumour biopsy. Oesophageal, gastric, colorectal and bile duct tumours were included, of seven molecular subtypes. Targeted next-generation sequencing and parallel whole-exome sequencing were used to identify validated resistance mechanisms. Cell-free DNA (cfDNA) identified resistance alterations in 76% of patients and 53% of these exhibited >1 resistance alteration. In the 23 patients who underwent both types of biopsy, 87% of cfDNA identified a resistance alteration versus 48% of tumour biopsies. Multiple alterations were only found in 9% of tumour biopsies. There was one resistance alteration detected by tumour biopsy which was not seen in cfDNA, although this was detected using a high-sensitivity assay. Five patients who underwent subsequent tumour biopsies showed the same resistance alterations seen in the earlier cfDNA. Patients who progressed on standard chemotherapy did not develop resistance alterations, hence these occur only under selective pressure. cfDNA represents resistance alterations from both the tumour and multiple metastatic lesions. Novel and non-genetic resistance mechanisms would not be detected by cfDNA, hence tumour biopsy continues to play a role. Liquid biopsy adds important information about acquired resistance and may be a tool to guide targeted molecular therapy in the future.

LECT2-Tie1 interactions are a novel therapeutic target for liver fibrosis

Xu M, Xu H-H, Lin Y, et al. LECT2, a ligand for Tie1, plays a crucial role in liver fibrogenesis. Cell 2019 Sep 5;178(6):1478–1492.e20. doi: 10.1016/j.cell.2019.07.021. (Epub ahead …