A patient with HER2-positive
metastatic breast cancer initially responds to trastuzumab therapy, with tumor
shrinkage observed on imaging. After six months, the tumor begins to regrow. A
biopsy of the recurrent tumor shows that the HER2 receptor is still expressed
but lacks the extracellular domain necessary for antibody binding, and
downstream MAPK/PI3K signalling remains active.

Which mechanism best explains the
observed resistance to trastuzumab?

Question

A patient with HER2-positive
metastatic breast cancer initially responds to trastuzumab therapy, with tumor
shrinkage observed on imaging. After six months, the tumor begins to regrow. A
biopsy of the recurrent tumor shows that the HER2 receptor is still expressed
but lacks the extracellular domain necessary for antibody binding, and
downstream MAPK/PI3K signalling remains active.

Which mechanism best explains the
observed resistance to trastuzumab?

Answer

Overexpression of
drug efflux pumps removing trastuzumab from the tumour microenvironment

Answer

Truncation
of the HER2 extracellular domain, preventing trastuzumab from binding and
inhibiting downstream signalling

Answer

Antibody-dependent
cell-mediated cytotoxicity eliminating immune cells rather than tumour cells

Answer

Loss-of-function
mutations in PI3K, reducing sensitivity to trastuzumab

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A patient with HER2-positive metastatic breast cancer initially responds to tra...

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