BRAF V600E

The frequencies of dMMR and Lynch syndrome in patients under 50 years old was comparable to our previous report in which testing was conducted as part of research. Our results suggest that in patients under 50 years old(, 1)the utility of BRAF testing as an adjunctive diagnostic tool for Lynch syndrome is limited, and (2)BRAFV600E or KRASG12C was not detected;however, a larger accumulation of cases is necessary.

P1/2, N=50, Recruiting, St. Justine's Hospital | Not yet recruiting --> Recruiting

Using high-throughput screening, we established that combining p38 inhibitors with the BRAF inhibitor dabrafenib showed strong synergy in vitro, including in cells resistant to dabrafenib and trametinib that had acquired a secondary TP53 mutation. Overall, our findings suggest an oncogenic link between the MAPK and p38/MAPK14 pathways and that combining p38 pathway inhibitors with dabrafenib-targeted therapy could improve treatment outcomes for aggressive thyroid cancers. However, more specific and effective p38 inhibitors are required to fully harness this potential.

BRAF-mut PTC is associated with a pro-inflammatory TME milieu compared to BRAF-wt PTC. However, in this limited data set, treatment choice was not associated with differences in OS in BRAF-mut PTC.

Multigene testing is underutilized in this population. While many targeted therapies carry a high risk of pneumonitis, sotorasib appeared relatively safe. Despite the risks, identifying and treating actionable oncogenic drivers may improve survival.

The greatest benefits of encorafenib plus binimetinib were observed in patients with evidence of high TMB and/or tumor immune infiltration, suggesting potential immune contributions to efficacy, which were not observed with vemurafenib. BRAF V600 detectability in ctDNA appears to have utility as a marker of prognosis and response in this population.

Advanced anal AD exhibited a distinct genomic profile compared with advanced rectal AD. CGP is a useful approach for identifying druggable GAs in advanced anal AD to expand therapeutic opportunities.

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

The data are in line with current literature that targeted treatment is being applied for selected LC patients in CZ. It can be expected that LC patients benefit from therapeutic and other clinical improvements, which however do not reduce the primary importance of anti-smoking campaigns.

However, SOX2 is uniquely upregulated in progenitor-derived tumours and is expressed in 20% of human cSCC, indicating it might mark tumours arising from committed progenitors. Here, we show that SOX2 overexpression, along with MAPK activation, in progenitors induces a stem-like state and renders this otherwise resistant population permissive to rapid transformation.

To our knowledge, this is the first report of dual TERTp mutations detected in the preoperative setting in thyroid carcinoma. Clinical correlation with future cases will be of interest, particularly if cases with monoallelic dual TERTp mutations are discovered.