Our results implicate BCL-xL, but not BCL-2 or MCL-1, as a central pro-survival factor of TIS cancer cells, as demonstrated by the BH3 profiling-based apoptotic dependency mapping of A549 TIS cancer cells and the nearly universal sensitivity of all the TIS phenotypes tested to the BCL-xL-specific inhibitor A1331852. Here, BCL2L1 is linked to cancer.