Overview of the essential kinase screening strategy. SCLC tumor specimens were injected subcutaneously into NSG mice to obtain primary PDX. PDX were harvested, infected with the shRNA kinome library and cultured in vitro, or reimplanted into NSG mice. DNA was extracted from shRNA infected cells at specified time points (in vitro) or tumor volumes (in vivo), shRNAs PCR amplified, and next generation sequencing performed to quantify the retained shRNAs. Lost, or depleted, shRNAs were considered as essential kinase candidates and validated for their essential function in vitro and in vivo.