Michael White's lab at UT Southwestern performed a large siRNA screen looking for genes that were preferentially required for cell viability in a lung tumor cell line model.  The results are interesting.  Few of the essential genes identified in one cell line were also essential across a panel of other lung tumor cell lines.  Further work revealed specific addictions to FLIP (an undruggable target, currently) in the small subset of NLRP3-mutated tumor cell lines, and addiction to lysosomal function in the small subset of KRAS + LBK1 mutant tumor cells.  It is becoming apparent that finding useful synthetic lethal interactions is very difficult and will require the search space to be broadened significantly, especially with respect to the mutations considered actionable.

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