Table 1. Examples of genes associated with drug resistance.
Gene | Function | Evidence for role in drug sensitivity | Reference |
---|---|---|---|
Apaf 1 | Proapoptotic, binds and promotes caspase 9 activation | Methylation in melanoma cells can be reversed by DNMT inhibitors and this is associated with increased sensitivity to doxorubicin | Soengas et al (2001) |
Caspase 8 | Proapoptotic | Frequently methylated in tumours. Reversal of methylation associated with increased sensitivity to doxorubicin, etoposide and cisplatin in Ewings sarcoma, neuroblastoma, medulloblastoma and melanoma cell lines | Fulda et al (2001) |
hMLH1 | DNA mismatch repair protein | Methylation and loss of expression associated with resistance to cisplatin in cell lines, which can be reversed by demethylation with decitabine. Increased frequency of methylation after chemotherapy. Acquisition of hMLH1 methylation during chemotherapy is independently associated with poor overall survival in ovarian patients | Gifford et al (2004) |
FancF | Activates DNA repair complex containing BRCA1, and BRCA2 loss cause a decreased ability to repair chemotherapy-induced damage | Methylation observed in cells with a defective BRCA2 pathway and increased sensitivity to cisplatin. Demethylation of FANCF with decitabine reduced sensitivity towards cisplatin in these cell line models | Taniguchi et al (2003) |
MGMT | Removes mutagenic alkyl-groups from the O6-position of guanine | Methylation and associated loss of expression correlates with response to temozolamide and BCNU in primary gliomas and overall and progression-free survival in patients with diffuse large B-cell lymphoma treated with cyclophosphamide-containing regimens | Paz et al (2004) |
MCJ | Unknown | Methylation associated with poor response to therapy and poor overall survival in ovarian patients | Strathdee et al (2005) |
ERβ | Methylated in 50% of invasive breast cancers. Methylation of ERβ less frequent and expression rate was higher in tamoxifen-resistant compared to control tumours | Chang et al (2005) |