Tamoxifen Plus Doxorubicin Shows Synergistic Kill of Mutant p53 Triple Negative Breast Cancer
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A preprint from Das et al. posted to bioRxiv on October 23, 2026 identifies a therapeutically actionable vulnerability in triple negative breast cancer (TNBC). Using genetic and pharmacological approaches, the authors show that tamoxifen synergizes with doxorubicin by strengthening the interaction between estrogen receptor beta and mutant p53. This disrupts the p73-mutant p53 complex, reactivating p73 and driving both apoptosis and ferroptosis in TNBC cells. In mutant p53 CDX and PDX models, the combination inhibited tumor growth. The work provides preclinical justification for repurposing tamoxifen alongside doxorubicin in molecularly stratified TNBC. Clinical testing in patients selected for mutant p53 status has not yet been reported.
Written by a model from the reports · updated 3 hours ago
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- biorxiv.orgTamoxifen and Doxorubicin Synergistically Target Estrogen Receptor beta-Mutant p53-p73 Axis, a Therapeutically Actionable Vulnerability in Triple Negative Breast Cancer
Das et al., using genetic and pharmacological approaches, showed that tamoxifen synergizes with doxorubicin in triple negative breast cancer (TNBC). Tamoxifen enhances the interaction between ER beta and mutant p53, disrupting the p73-mutant p53 complex, reactivating p73, and inducing apoptosis and ferroptosis, which inhibits tumor growth in mutant p53 CDX and PDX models. The study provides preclinical rationale for repurposing tamoxifen combined with doxorubicin in molecularly stratified TNBC. DOI: 10.64898/2026.10.21.760572v1.
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