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