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Issue 167: Cell cycle inhibitor therapies have shown promise in treating metastatic estrogen receptor positive breast cancers. However, its efficacy in treating potentially curable earlier stage tumors is highly variable. To understand the cancer cell phenotypes that convey resistance, we analyzed the gene expression of individual cancer cells extracted from patient biopsies before, during and after treatment. Using hierarchical models, we uncovered that as tumors become resistant (from figure’s left (sensitive) to right (resistant)), estrogen receptor signalling (pink points) is reduced and cancer cells upregulate alternative growth factor receptors (purple points). This activates alternate pathways transducing the proliferative signal to the nucleus (white versus red core), allowing cell cycle inhibition to be bypassed and jointly conveys resistance to standard of care estrogen therapies. See the full publication in Nature Cancer.