biostudies-literatureVarady AÖsterreichische ForschungsförderungsgesellschaftAustrian Science Fund FWFAlex's Lemonade Stand Foundation for Childhood CancerÖsterreichischen Akademie der WissenschaftenSt. Anna Children's Cancer Research InstituteDMM052016https://www.ebi.ac.uk/biostudies/studies/S-EPMC11892682biostudies-literatureUnknown18(2)Owing to their high efficacy, antimitotic chemotherapeutics are the mainstay for most cancer treatments. However, these drugs do not discriminate between tumor and healthy cells, thus show dose-limiting toxicity and severe adverse effects. To improve treatments, rendering chemotherapeutics tumor-cell specific is highly desirable. Although various strategies, such as targeted antibody-drug conjugates, aim to achieve this goal, the identification of a tumor-specific 'Achilles' heel' remains a challenge. Here, we followed an alternative approach, which does not rely on tumor-specific characteristics, but rather uses spatially confined illumination of the light-activatable microtubule inhibitor SBTubA4P to target its cytotoxic activity to tumor cells. We demonstrate that localized illuminationDisease models & mechanismsPrecise photopharmacological eradication of metastatic tumor cells.PMC11892682794062820-17258P30038-BBLVarady ASchmitner NPoplimont HSturtzel CGao LDistel MKimmel RAGrissenberger SWenninger-Weinzierl AfalsePrecise photopharmacological eradication of metastatic tumor cells.Owing to their high efficacy, antimitotic chemotherapeutics are the mainstay for most cancer treatments. However, these drugs do not discriminate between tumor and healthy cells, thus show dose-limiting toxicity and severe adverse effects. To improve treatments, rendering chemotherapeutics tumor-cell specific is highly desirable. Although various strategies, such as targeted antibody-drug conjugates, aim to achieve this goal, the identification of a tumor-specific 'Achilles' heel' remains a challenge. Here, we followed an alternative approach, which does not rely on tumor-specific characteristics, but rather uses spatially confined illumination of the light-activatable microtubule inhibitor SBTubA4P to target its cytotoxic activity to tumor cells. We demonstrate that localized illumination2025-01-01T00:00:00Z2025 Feb2026-05-29T12:46:29.662Z2025-04-05T23:53:16.938ZS-EPMC118926824001405110.1242/dmm.052016