In a cell culture dish, a researcher
studies medulloblastoma cells derived from a patient with PTCH
loss-of-heterozygosity (LOH). When treated with a SMO inhibitor, most cells in
culture die initially. After several weeks, in the presence of the inhibitor, a
small number of cells begins to
proliferate rapidly. Molecular analysis reveals that the Hedgehog pathway is
reactivated despite drug treatment. Which explanation best accounts for
the observed drug resistance?

Question

In a cell culture dish, a researcher
studies medulloblastoma cells derived from a patient with PTCH
loss-of-heterozygosity (LOH). When treated with a SMO inhibitor, most cells in
culture die initially. After several weeks, in the presence of the inhibitor, a
small number of  cells begins to
proliferate rapidly. Molecular analysis reveals that the Hedgehog pathway is
reactivated despite drug treatment. Which explanation best accounts for
the observed drug resistance?

Accepted Answer

Mutations
in Smoothened prevent inhibitor activity, allowing constitutive Hedgehog
pathway activation despite drug treatment

Answer

The PTCH mutation
spontaneously reverted to wild-type, restoring normal Hedgehog inhibition

Answer

The cells bypass
Hedgehog signalling by inactivating EGFR or other receptor tyrosine kinase
pathways

Answer

The surviving cells overexpress
drug efflux pumps, increasing intracellular inhibitor levels

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In a cell culture dish, a researcher studies medulloblastoma cells derived from...

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