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When triple-negative breast cancer became resistant to sacituzumab govitecan in one patient, one branch of the tumour had changed the drug's payload target and a different branch had changed TROP2 itself.
RNA and whole-exome sequencing of tumour specimens before treatment and after progression on sacituzumab govitecan in triple-negative breast cancer. A patient with de novo progression lacked TROP2 expression, while a patient with a deep, prolonged response had robust TROP2 expression and focal amplification of TACSTD2, the TROP2 gene. At acquired resistance in that patient, one phylogenetic branch carried the canonical TOP1 E418K resistance mutation and a later frameshift TOP1 mutation, while a distinct branch carried a new TACSTD2 T256R missense mutation. Reconstitution experiments showed that T256R causes resistance through defective plasma membrane localisation and reduced cell-surface binding by hRS7, the antibody in the drug.
Resistance can come from different subclones in the same person, each with its own mechanism, and one of them changed the TROP2 protein itself. It is the clearest published link between a residual clone and a TROP2 phenotype, made from tissue at progression rather than from blood.
Shares Read methylation and mutation on the same cell-free DNA fragment to tell what kind of cancer is left, Naming which clone or phenotype is left after treatment, Sacituzumab govitecan, TROP2.
Shares Sacituzumab govitecan, TROP2, Triple-negative breast cancer (TNBC).
Shares Sacituzumab govitecan, TROP2.
Shares Cancer Discovery, Triple-negative breast cancer (TNBC).
Shares Naming which clone or phenotype is left after treatment, TROP2, Triple-negative breast cancer (TNBC).
Shares Sacituzumab govitecan, TROP2.
Shares Sacituzumab govitecan, TROP2.
Shares Read methylation and mutation on the same cell-free DNA fragment to tell what kind of cancer is left, Naming which clone or phenotype is left after treatment.
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