A patient with medulloblastoma caused
by loss of heterozygosity (LOH) of PTCH is treated with a Smoothened (SMO)
inhibitor. The tumour initially shrinks, but over time it resumes growth.
Molecular analysis reveals that the Hedgehog pathway is reactivated, despite
drug treatment.

Which mechanism most likely explains
the development of drug resistance?

Question

A patient with medulloblastoma caused
by loss of heterozygosity (LOH) of PTCH is treated with a Smoothened (SMO)
inhibitor. The tumour initially shrinks, but over time it resumes growth.
Molecular analysis reveals that the Hedgehog pathway is reactivated, despite
drug treatment.

Which mechanism most likely explains
the development of drug resistance?

Answer

Reversion of the PTCH
mutation back to wild-type

Answer

Acquisition
of a mutation in Smoothened that prevents inhibitor activity

Answer

Inactivation of an
alternative receptor tyrosine kinase pathway, such as EGFR

Answer

Increased expression
of multidrug efflux pumps that enhance intracellular inhibitor concentration

Crowdly

A patient with medulloblastoma caused by loss of heterozygosity (LOH) of PTCH i...

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