In our previous work, we identified the HSP90 cofactor, CDC37, as one of the top GIST-specific essential genes by parallel genome-scale short-hairpin RNA (shRNA)-mediated gene knockdowns in GIST-T1 and GIST882.35 Subsequent functional evaluations highlighted that CDC37 is a crucial regulator of KIT oncoproteins in both imatinib-sensitive and imatinib-resistant GIST, and thus represents a promising strategy for inactivating the heterogeneous mutant KIT oncoproteins in TKI-resistant GIST patients. The gene discussed is KIT; the disease is gastrointestinal stromal tumor.