To follow the progression of digestion we further subtracted FTIR spectra of residual cell walls after 72 h of incubation from FTIR spectra of residue of cell walls after 6 h of incubation.
For Patient #2, partial hits are defined as drugs residual cell viability > 25% and ≤ (Staurosporine + 5%) at 1 µM.
Twenty-one out of 34 patients experienced transient fever, possibly due to exposure to residual cell culture or labeling materials.
We found a moderate response, comparable to the effect of Staurosporine (~40% residual cell viability), to EGFR/HER2 inhibitors including Lapatinib and WZ8040 (Table 2).
Hits are determined following three criteria: (1) cell death shows concentration dependency, (2) residual cell viability at 1 µM is ≤ 25%, and (3) average Z-score ≤ − 5.
In our screening, the PDTOs established from this tumor responded to ~3% of all tested kinase inhibitors (7/240, residual cell viability ≤ 25%, and average Z-score ≤ − 1.5), including CDK inhibitors and phosphatidyl inositol 3-kinase (PI3K) inhibitors.
The PDTOs showed a strong response (residual cell viability ≤ 25% and average Z-score ≤ − 5) to only 0.8% of all drugs tested (2/240, Fig. 4a, Table 2, and Supplementary Fig. 7a).
Furthermore, residual cell nuclei did not correlate to residual antigenicity, demonstrating that residual nuclei counts may not be an appropriate indicator of successful AR.
The organoids were however sensitive to ~6% of the protein kinase inhibitors tested (16/240), with sensitivity defined as residual cell viability ≤ 25% and average Z-score ≤ − 5 (Table 1, Supplementary Table 2, Supplementary Fig. 7a; see Methods for Z-score calculations).
The residual cell wall was washed with 70%% ethanol, vortexed and centrifuged at 15,000 rpm for 5 min.
