Publications by authors named "L Gaughan"
Circulating tumor DNA (ctDNA) in plasma cell free DNA (cfDNA) of cancer patients is associated with poor prognosis, but is challenging to detect from low plasma volumes. In metastatic castration-resistant prostate cancer (mCRPC), ctDNA assays are needed to prognosticate outcomes of patients treated with androgen receptor (AR) inhibitors. We develop a custom targeted cfDNA sequencing assay, named AR-ctDETECT, to detect ctDNA in limiting plasma cfDNA available from mCRPC patients in the Alliance A031201 randomized phase 3 trial of enzalutamide with or without abiraterone.
View Article and Find Full Text PDFResistance to androgen receptor (AR)-targeted therapies represents a major challenge in prostate cancer. A key mechanism of treatment resistance in patients who progress to castration-resistant prostate cancer (CRPC) is the generation of alternatively spliced AR variants (AR-V). Unlike full-length AR isoforms, AR-Vs are constitutively active and refractory to current receptor-targeting agents and hence drive tumor progression.
View Article and Find Full Text PDFImmune checkpoint blockade has yet to produce robust anti-cancer responses for prostate cancer. Sialyltransferases have been shown across several solid tumours, including breast, melanoma, colorectal and prostate to promote immune suppression by synthesising sialoglycans, which act as ligands for Siglec receptors. We report that ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) levels negatively correlate with androgen signalling in prostate tumours.
View Article and Find Full Text PDFArticle Synopsis
- * A specific example shows that when histone H3 is phosphorylated at threonine-3 (H3T3ph), it prevents certain reader proteins from binding to adjacent modified histones, particularly affecting TAF3's role in transcription.
- * Genome-wide analysis during cell division reveals that H3T3ph actually reduces the presence of H3K4me2/3 in cells, indicating that H3T3ph is not responsible for inhibiting transcription during mitosis despite expectations from in vitro studies.
Article Synopsis
- * AR-Vs activate androgenic signaling independently and resist existing therapies, highlighting the need for new treatment strategies targeting their function.
- * The study identifies DNA-PKcs as a crucial element in regulating AR-V activity and suggests that targeting this protein may effectively reduce AR-V signaling in advanced PC, offering a promising therapeutic avenue for resistant cases.