TABLE 2.
Therapy strategy development based on lung organoids.
| Therapy | Drug | Target | Mechanism | Preclinical study or clinical trial | Reference |
|---|---|---|---|---|---|
| PARP inhibitor | Olaparib | BRCA2 p.W2619C NSCLC | NA | NA | PMID: 31488816 |
| EGFR tyrosine kinase inhibitors | Erlotinib | EGFR-mutant NSCLC | NA | NA | PMID: 31488816 |
| c-Met inhibitor | Crizotinib | EGFR-mutant/MET-amplified organoid NSCLC | NA | NA | PMID: 31488816 |
| ERBB2 inhibitor and RET-fusion inhibitor | Poziotinib, pralsetinib | Lung adenocarcinoma harboring ERBB2 exon 20 insertions or RET fusions, respectively | NA | Clinical trial registration: NCT02609776 | PMID: 34083237 |
| EGFR-MET Bispecific Antibody | Amivantamab (JNJ-61186372) | EGFR Exon 20 Insertion NSCLC | Amivantamab Induces Antibody-Dependent Cell-Mediated Cytotoxicity | NA | PMID: 32414908 |
| PMID: 34339292 | |||||
| Targeting the AGO-KRAS interaction | NA | KRASG12D-driven NSCLC | Ago2 ablation suppresses KRAS signaling in NSCLC | NA | PMID: 33972443 |
| Cyclin-dependent kinase 7 inhibitor | YPN-005 | SCLC | YPN-005 significantly decreases the phosphorylation of the carboxyl-terminal domain of RNA polymerase II | NA | PMID: 34224696 |
| Rescuing histone and DNA hypomethylation | SAM | SCLC | SAM rescues KMT2C-loss-initiated epigenetic reprogramming | Clinical trial registration: NCT02535507 | PMID: 35449309 |
| pan-HER receptor tyrosine kinase inhibitor | Pyrotinib | HER2 exon 20 insertions in NSCLC | NA | NA | PMID: 30596880 |
| WEE1 Kinase Inhibitor | AZD1775 | LKB1-Deficient NSCLC | Loss of ATM phosphorylation of LKB1 contributes to AZD1775 + cisplatin sensitivity | NA | PMID: 28652249 |
| MEK inhibitor | Trametinib, selumetinib | KRAS mutation and amplification NSCLC | NA | NA | PMID: 31694835 |
| Combining FGFR and MEK inhibitors | BGJ398+trametinib combination | FGFR1 amplified LUSC | NA | NA | PMID: 31694835 |
| TMPRSS2 as an attractive pan-coronavirus therapeutic target | NA | pan-coronaviruses | Knockout of TMPRSS2 effectively blocks viral replication | NA | PMID: 34535662 |
| Low-dose IFN pre-treatment | IFN | SARS-CoV-2 | NA | NA | PMID: 33128895 |
| Entry inhibitors of SARS-CoV-2 | Imatinib, MPA, and QNHC | SARS-CoV-2 | Imatinib and QNHC bind with ACE2; MPA and QNHC treatment decrease the expression levels of FURIN | NA | PMID: 33116299 |
| Blocking SARS-CoV-2 infection | GW6471 | SARS-CoV-2 | GW6471 inhibits the HIF1ɑ-glycolysis axis | NA | PMID: 34731648 |
| Pan-ErbB inhibitor | Lapatinib | SARS-CoV-2 | ErbB4 is required for SARS-CoV-2 entry | NA | PMID: 34159337 |
| VimIF assembly inhibitor | Withaferin A | IPF | WFA reduces the invasiveness of lung fibroblasts | NA | PMID: 30944258 |
| IL-11 as a therapeutic target | NA | IPF | IL-11 induces fibrosis in WT organoids, while its deletion prevented fibrosis in HPS4−/− organoids | NA | PMID: 31216486 |
| ALK5 inhibitor and integrin ɑVβ6 antagonist | SB525334, GSK3008348 | IPF | ALK5 inhibitors and integrin αVβ6 antagonists suppress TGFβ signaling | NA | PMID: 34798066 |
| Notch2 blockade as a therapeutic strategy | NA | GCM (such as asthma, COPD, and CF) | Antibodies that specifically inhibit Notch2, inhibit IL-13-driven goblet cell metaplasia in vitro and in vivo | NA | PMID: 25558064 |
NA, not available; VimIF, vimentin intermediate filament; MPA, mycophenolic acid; QNHC, quinacrine dihydrochloride; SAM, S-Adenosyl methionine; SCLC, small cell lung cancer; NSCLC, non-small cell lung cancer; LUSC, lung squamous cell carcinoma; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; IPF, idiopathic pulmonary fibrosis; GCM, goblet cell metaplasia; COPD, chronic obstructive pulmonary disease; CF, cystic fibrosis.