Publications by authors named "S Siena"
Patients diagnosed with metastatic colorectal cancer (mCRC) have a poor prognosis with survival ranging 2-3 years. The prevalence of human epidermal growth factor receptor 2 (HER2) amplification is approximately 3-4% in mCRC and increases up to 8% in patients with // wild-type (WT) CRC tumors. Tucatinib is a highly selective HER2-directed tyrosine kinase inhibitor that, in combination with trastuzumab, has demonstrated clinically meaningful activity in patients with chemotherapy-refractory, HER2-positive (HER2+), WT mCRC in the MOUNTAINEER trial.
View Article and Find Full Text PDFis responsible for the direct repair of O6-methylguanine lesions induced by alkylating agents, including temozolomide. promoter hypermethylation is a well-established biomarker for temozolomide response in glioblastoma patients, also correlated with therapeutic response in colorectal cancer. The ARETHUSA clinical trial aims to stratify colorectal cancer patients based on their mismatch repair status.
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- DESTINY-CRC01 was a multicenter phase 2 study examining the safety and effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic colorectal cancer.
- The exploratory biomarker analysis identified correlations between higher HER2 biomarker levels and improved clinical outcomes, such as response rate and overall survival, in patients with HER2-positive tumors.
- Circulating tumor DNA analysis indicated that T-DXd may also be effective in patients with specific genetic mutations (RAS, PIK3CA, or HER2) detected in their ctDNA.
Article Synopsis
- The study highlights the interest in PARP inhibitors for treating tumors with "BRCAness," particularly in colorectal cancers, as approximately 15% possess defects in the homologous recombination (HR) pathway, presenting new treatment opportunities.
- The researchers developed HRDirect, an advanced tool for predicting HR deficiency (HRD) in tumor samples, which outperformed existing assays by accurately identifying resistant colorectal cancer models.
- The study suggests a composite biomarker approach combining HRDirect scoring with ATM and RAD51C analysis to improve HRD tumor identification and enhance personalized treatment strategies for colorectal cancer patients.
Background: Sustained clinical complete remissions were reported in all of 23 mismatch repair deficient/microsatellite instable (dMMR/MSI) locally advanced rectal cancer (LARC) patients treated with dostarlimab alone in a recent phase II study. These results led to off-label use of dostarlimab or other immune checkpoint inhibitors (ICIs) in dMMR/MSI-LARC even before regulatory approval. The present study [STAR(t)-IT-REDUCE] describes the outcome of dMMR/MSI-LARC patients treated with ICI in Italy.
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