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Target Overview
FRα is a cell surface protein that binds and internalizes folate, a cofactor required for DNA synthesis, cell growth, and proliferation. Normal adult tissues generally lack FRα expression. In contrast, FRα is highly expressed in multiple epithelial tumors, including ovarian cancer and lung adenocarcinoma.1-4
Compound Overview
Torvutatug samrotecan (AZD5335) is a specific, targeted antibody-drug conjugate that binds with high affinity to FRα and delivers a potent topoisomerase 1 inhibitor (TOP1i) payload across a broad range of FRα expression levels. Upon internalization and trafficking to the lysosome, the TOP1i payload is released into the cell where it traps TOP1 on DNA, ultimately resulting in tumor cell death. The TOP1i payload can also diffuse through the cell membrane to exert bystander anti-tumor activity. Torvutatug samrotecan is currently under investigation as a monotherapy and in combination with other therapeutic agents.5,6
Mechanism of Action
References
1. Weitman SD et al. Cancer res. 1992;52(12):3396-3401. 2. Mantovani L et al. Eur J of Cancer. 1994;30(3):363369. 3. Kelemen LE et al. Int J Cancer. 2006;119(2):243250. 4. Elnakat H et al. Adv drug deliv rev. 2004;56(8):10671084. 5. Zoeller JJ et al. Clin Cancer Res. 2025;31(24):5261-5275. 6. Oaknin A. Presented at ESMO; October 17-21, 2025; Berlin, Germany. Abstract: 1065MO.
Target Overview
FRα is a cell surface protein that binds and internalizes folate, a cofactor required for DNA synthesis, cell growth, and proliferation. Normal adult tissues generally lack FRα expression. In contrast, FRα is highly expressed in multiple epithelial tumors, including ovarian cancer and lung adenocarcinoma.1-4
Compound Overview
Torvutatug samrotecan (AZD5335) is a specific, targeted antibody-drug conjugate that binds with high affinity to FRα and delivers a potent topoisomerase 1 inhibitor (TOP1i) payload across a broad range of FRα expression levels. Upon internalization and trafficking to the lysosome, the TOP1i payload is released into the cell where it traps TOP1 on DNA, ultimately resulting in tumor cell death. The TOP1i payload can also diffuse through the cell membrane to exert bystander anti-tumor activity. Torvutatug samrotecan is currently under investigation as a monotherapy and in combination with other therapeutic agents.5,6
Mechanism of Action
References
1. Weitman SD et al. Cancer res. 1992;52(12):3396-3401. 2. Mantovani L et al. Eur J of Cancer. 1994;30(3):363369. 3. Kelemen LE et al. Int J Cancer. 2006;119(2):243250. 4. Elnakat H et al. Adv drug deliv rev. 2004;56(8):10671084. 5. Zoeller JJ et al. Clin Cancer Res. 2025;31(24):5261-5275. 6. Oaknin A. Presented at ESMO; October 17-21, 2025; Berlin, Germany. Abstract: 1065MO.
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Abbreviations
DNA
deoxyribonucleic acid
FRα
folate receptor α
NSCLC
non-small cell lung cancer
TOP1i
topoisomerase 1 inhibitor