Molecular mechanisms of chemoresistance in medulloblastoma

Abstract

The design of medulloblastoma therapy has become more and more sophisticated over the past 30 years. Despite this, a significant proportion of patients continue to die from this disease, with drug resistance and relapse still observed. Resistance to treatment with anticancer drugs results from a variety of factors including individual genetic variations in patients and acquired resistance. We here review the most common reasons for drug resistance in medulloblastoma cells. We will cover the acquisition of drug resistance towards the classical chemotherapeutic drugs used in medulloblastoma due to modification of enzymatic activities such as alkyl tranferase, gluthatione tranferase, phosphatidyl-inositol-3-kinase or to expression of energy-dependent transporters that eject anticancer drugs from cells. We will also review other mechanisms of resistance including insensitivity to drug-induced cell death due to genetic mutations in crucial signaling pathways such as NF-kappaB and p53.