CSK and breast carcinoma: Once an interesting hit, CSK, was identified, the authors performed a second screen to find genes synthetically lethal with loss of CSK. Ultimately, they identified a feedback loop that limits the efficacy of endocrine therapies where CSK is induced by oestrogen, and in the absence of oestrogen, cells have low levels of CSK, which activates protein-activated kinase 2 (PAK2), driving breast cancer growth.