2 research outputs found
Molecular purging of multiple myeloma cells by culture and retroviral transduction of mobilized-blood CD34cells-2
<p><b>Copyright information:</b></p><p>Taken from "Molecular purging of multiple myeloma cells by culture and retroviral transduction of mobilized-blood CD34cells"</p><p>http://www.translational-medicine.com/content/5/1/35</p><p>Journal of Translational Medicine 2007;5():35-35.</p><p>Published online 12 Jul 2007</p><p>PMCID:PMC1948885.</p><p></p>transduced cells. (B) Relative fold expansion in culture, and recovery after transduction and selection of total cells (open bars) and CD34+ cells (black bars), were measured, in comparison with the initial cell population (fresh cells)
Codon-specific KRAS mutations predict survival benefit of trifluridine/tipiracil in metastatic colorectal cancer.
Genomics has greatly improved how patients with cancer are being treated; however, clinical-grade genomic biomarkers for chemotherapies are currently lacking. Using whole-genome analysis of 37 patients with metastatic colorectal cancer (mCRC) treated with the chemotherapy trifluridine/tipiracil (FTD/TPI), we identified KRAS codon G12 (KRASG12) mutations as a potential biomarker of resistance. Next, we collected real-world data of 960 patients with mCRC receiving FTD/TPI and validated that KRASG12 mutations were significantly associated with poor survival, also in analyses restricted to the RAS/RAF mutant subgroup. We next analyzed the data of the global, double-blind, placebo-controlled, phase 3 RECOURSE trial (nβ=β800 patients) and found that KRASG12 mutations (nβ=β279) were predictive biomarkers for reduced overall survival (OS) benefit of FTD/TPI versus placebo (unadjusted interaction Pβ=β0.0031, adjusted interaction Pβ=β0.015). For patients with KRASG12 mutations in the RECOURSE trial, OS was not prolonged with FTD/TPI versus placebo (nβ=β279; hazard ratio (HR)β=β0.97; 95% confidence interval (CI)β=β0.73-1.20; Pβ=β0.85). In contrast, patients with KRASG13 mutant tumors showed significantly improved OS with FTD/TPI versus placebo (nβ=β60; HRβ=β0.29; 95% CIβ=β0.15-0.55; PβG12 mutations were associated with increased resistance to FTD-based genotoxicity. In conclusion, these data show that KRASG12 mutations are biomarkers for reduced OS benefit of FTD/TPI treatment, with potential implications for approximately 28% of patients with mCRC under consideration for treatment with FTD/TPI. Furthermore, our data suggest that genomics-based precision medicine may be possible for a subset of chemotherapies