Co-evolution of atypical BRAF and KRAS mutations in colorectal tumorigenesis.

BRAF mutations in colorectal cancer (CRC) comprise three functional classes: Class 1 (V600E) with strong constitutive activation, Class 2 with pathogenic kinase activity lower than Class 1, and Class 3 which paradoxically lacks kinase activity. Non-Class 1 mutations associate with better prognosis, microsatellite stability, distal tumour location and better anti-EGFR response. Analysis of 13 CRC cohorts (n=6,605 tumours) compared Class 1 (n=709, 10.

Tumour purity assessment with deep learning in colorectal cancer and impact on molecular analysis.

Tumour content plays a pivotal role in directing the bioinformatic analysis of molecular profiles such as copy number variation (CNV). In clinical application, tumour purity estimation (TPE) is achieved either through visual pathological review [conventional pathology (CP)] or the deconvolution of molecular data. While CP provides a direct measurement, it demonstrates modest reproducibility and lacks standardisation.

TEX264 drives selective autophagy of DNA lesions to promote DNA repair and cell survival.

DNA repair and autophagy are distinct biological processes vital for cell survival. Although autophagy helps maintain genome stability, there is no evidence of its direct role in the repair of DNA lesions. We discovered that lysosomes process topoisomerase 1 cleavage complexes (TOP1cc) DNA lesions in vertebrates.

Standard or high dose chemoradiotherapy, with or without the protease inhibitor nelfinavir, in patients with locally advanced pancreatic cancer: The phase 1/randomised phase 2 SCALOP-2 trial.

Background: The multi-centre two-stage SCALOP-2 trial (ISRCTN50083238) assessed whether dose escalation of consolidative chemoradiotherapy (CRT) or concurrent sensitization using the protease inhibitor nelfinavir improve outcomes in locally advanced pancreatic cancer (LAPC) following four cycles of gemcitabine/nab-paclitaxel.

Methods: In stage 1, the maximum tolerated dose (MTD) of nelfinavir concurrent with standard-dose CRT (50.4 Gy in 28 fractions) was identified from a cohort of 27 patients.