Overcoming cisplatin resistance in TP53-null colon cancer organoids
Cisplatin chemotherapy in colorectal cancer (CRC) often fails due to drug resistance, particularly in TP53-deficient tumours as TP53 mutations impair apoptotic responses. By leveraging Oxford Nanopore sequencing and CRISPR-based functional genomics, Khalili et al. uncovered new therapeutic targets for TP53-null CRC. While still in the early stages, this research has the potential to improve patient outcomes through targeted treatment strategies in the future.
Key points:
Tumour cells with TP53 mutations compensate for DNA damage by relying on alternative repair pathways
Using a genome-wide CRISPR knockout screen, researchers pinpointed DNA repair pathway genes, including FANCL, ERCC6, and BRIP1, as key mediators of drug resistance
Oxford Nanopore sequencing validated CRISPR screening results, providing high-resolution confirmation of guide RNA depletion and structural changes in resistant tumour cells
Inhibition of FANCL, ERCC6, and BRIP1 significantly increased cisplatin sensitivity, suggesting that blocking these pathways could potentially enhance chemotherapy effectiveness
This research supports precision oncology, demonstrating how genetic profiling could guide personalised therapies in the future
Sample type: colon cancer organoids
Kit: Native Barcoding Kit