a Heterogeneous responses of organoids derived from lung adenocarcinomas to the cisplatin-based chemotherapies. The fitted dose–response curves illustrate the responses of the AC organoids to pemetrexed + cisplatin (PC) and gemcitabin + cisplatin (GC) (n = 3 biologically independent cells, data are presented as mean ± SD). The heat map on the right are examples of two organoids sensitive to PC and the other two sensitive to GC. R means the IC50 is not available. b LCO-based on-chip drug sensitivity tests representing the responses of patient tumors to chemotherapies. The CT images on the left are a lung squamous cell carcinoma sensitive to the GC therapy. The red circles indicate the primary tumor and the red arrows point to the metastatic lymph nodes, both of which shrank upon the GC treatment. The CT scan images on the right showed a lung squamous cell carcinoma resists the GC therapy. The red arrows point to the station L2 lymph nodes where new metastasis was discovered after two cycles of adjuvant chemotherapy with GC. c Fitted the dose–response curves of the LCOs representing the diverse responses of the in vivo tumors to the chemotherapy (n = 3 biologically independent cells, data are presented as mean ± SD). d LCO-based on-chip screening of anticancer drugs effective to individual patients. e On-chip drug screening using the organoid line (LC96-O). The CT scan images showed the patient tumor metastasized to bone (red circles) and lymph node (red arrows) during chemotherapy with PC. f Drug–response curves on the left showing the results of the on-chip screening of three chemotherapies (PC, GC, and paclitaxel + cisplatin) using the LC96-O. The line charts on the right represent the tumor volume of the PDX exposed to the same chemotherapies as the LCOs. Both of the results consistently showed that none of the drug combinations could inhibit the growth of the tumor effectively (n = 3 biologically independent LCOs in the left panel; n = 4 biologically independent animals in the right panel, data are presented as mean ± SD).