Extended Data Fig. 10: Application of PDxO screening to precision oncology.

(a) Representative imaging data (upper panel) and a timeline representing the natural history of individual HCI-043’s breast cancer (lower panel) Events are as follows: A. Diagnosis of early recurrent disease metastatic to the liver (solid arrow). No skeletal metastases (empty arrow). B. No response to capecitabine; new onset skeletal metastases (empty arrow). C. Initiation of cabozantinib and atezolizumab; liver metastases still present (solid arrows). D. No response to cabozantinib and atezolizumab; progression of the hepatic metastases (solid arrow) and production of malignant ascites (empty arrows). E. After 3 cycles of the PDxO-informed eribulin treatment, the patient achieved a complete radiographic remission of the hepatic metastases (solid arrows). The malignant ascites also regressed somewhat (empty arrow). F. After 5 cycles on eribulin, there was complete remission of the malignant ascites (empty arrow) and continued complete remission of the hepatic metastases (solid arrow). However, new onset isolated metastasis in T12 vertebrae (arrowhead) required discontinuation of eribulin and treatment with radiation therapy. G. Recurrence of the hepatic metastases 2 months after withholding the eribulin (solid arrows). (b) H&E staining and PD-L1 staining of HCI-043 patient’s tumor. The tumor tested low but positive for PD-L1 on the basis of an FDA-approved commercially available test. Due to the nature of the test a scalebar is not available. (c) (upper panel) RNA-seq data showing expression of genes associated with the luminal androgen receptor (LAR) subtype in HCI-043 patient tumor. (lower panel) scRNA-seq data showing androgen receptor (AR) expression (red; left side) in all tumor cell clusters (middle) in HCI-043 PDX and PDxOs. Immunohistochemistry for the androgen receptor on the patient tumor was detected by a commercial vendor (PhenoPath; right side). (d-e) Dose response heatmaps showing results of drug screening on the pre-treatment breast tumor biopsy model HCI-043 (d) and the post-treatment metastatic ascites sample (e) from timepoint D on the timeline in panel a, HCI-051. Coloration of these heatmaps indicates CellTiter-Glo 3D cell viability assays that were normalized to day 0 ranging from black (cytotoxic) to yellow (growth), which have been scaled respectively. The drug order on both plots is sorted by GRaoc.