Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM.

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75-78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.

Pyrolysis of Furan and Its Methylated Derivatives: A Shock-Tube/TOF-MS and Modeling Study.

In this study, the pyrolysis of furan (F) and its two methyl-substituted derivatives 2-methylfuran (2-MF) and 2,5-dimethylfuran (2,5-DMF) was investigated behind reflected shock waves at pressures near 1 bar in Ne as the bath gas. Concentration-time profiles of different stable species (reactants, intermediates, and products) were recorded simultaneously with high-repetition time-of-flight mass spectrometry and compared to results from simulations with a recently published, combined F/2-MF/2,5-DMF oxidation mechanism that was slightly modified already in another publication to describe the formation of H atoms in these pyrolysis systems. The temperature ranges covered in our experiments were chosen in line with the different thermal stabilities of the three reactants (F: T = 1050-1920 K; 2-MF: T = 1060-1900 K; 2,5-DMF: T = 1000-1800 K). In general, we obtained satisfactory agreement of the experimental and modeling results. To clarify the most important reaction routes for the formation of the detected species, we performed extensive sensitivity and rate-of-production analyses. The influence of increasing methylation of the furan ring on the formation and consumption of the different species is discussed in detail. Experimental concentration-time profiles are given in tabular form in the Supporting Information to enable tests of future mechanism developments.