Simon F. Roy

Scientific independence alone does not create a sustainable research program. Drawing on the 2026 Irving Cancer Immunology Symposium, we offer practical strategies for navigating uncertainty and limited resources to build a coherent research program and resilient team across funding systems.

DepMap HMGCR gene expression and gene effect scores for 1,078 cancer cell lines

Mevalonate pathway activity distinguishes treatment response in melanoma tumor cells.

Confocal Z-stack image of cells treated with MEK inhibitor

Confocal Z-stack image of cells treated with DMSO

Statins have been reported to exert anticancer activity, varying with cancer type and specific statins. These findings suggest that more mechanistic insights into the anticancer effects of statins are needed. In this study, we interrogated the ability of statins to induce cell death and ferroptosis in melanoma and colorectal cancer. First, we showed that statins induce cell death in patient-derived melanoma cell lines and that lower expression of mevalonate pathway genes correlates with increased CD8+ T-cell infiltration and improved overall survival in patients with melanoma. We found that lipophilic statins induce cell death with features of ferroptosis. Transcriptional data also revealed system-level changes to a variety of ferroptosis-related pathways. We found that mevalonate rescued statin-induced cell death. Mechanistically, mevalonate-derived isopentyl pyrophosphate is necessary for isopentylation of tRNA [Ser]Sec, which is required for efficient synthesis of the selenoprotein ferroptosis suppressor GPX4. Given the emerging role for ferroptosis in antitumor immunity, we tested lipophilic statins, including simvastatin, alone and in combination with α-PD1 in vivo and found that simvastatin and α-PD1 promoted tumor clearance and extended survival in 20% to 60% of mice alone but in nearly 100% of mice when administered together. Simvastatin also depleted GPX4 in vivo. These results highlight the therapeutic potential of statin use in combination with immunotherapies.

Time-lapse video with and without ERK inhibition

Statins suppress GPX4 expression and mevalonate rescues statin-induced cell death