Oxaliplatin: pre-clinical perspectives on the mechanisms of action, response and resistance

Oxaliplatin is a third-generation platinum compound that has shown a wide range of anti-tumour activity in metastatic cancer and in multiple cell lines. It contains a diaminocyclohexane carrier ligand and is one of the least toxic platinum agents. In the past decade, the use of oxaliplatin for the treatment of colorectal cancer has become increasingly popular because neither cisplatin nor carboplatin demonstrate significant activity. Similar to cisplatin, oxaliplatin binds to DNA, leading to GG intra-strand crosslinks. Oxaliplatin differs from its parent compounds in its mechanisms of action, cellular response and development of resistance, which are not fully understood. Like most chemotherapeutic agents, efficacy of oxaliplatin is limited by the development of cellular resistance. ERCC1 (excision repair cross-complementation group 1) mediated nucleotide excision repair pathway appears to be the major pathway involved in processing oxaliplatin, because the loss of mismatch repair does not lead to oxaliplatin resistance. Recent findings support the involvement of many genes and different pathways in developing oxaliplatin resistance. This mini-review focuses on the effects of oxaliplatin treatment on cell lines with special emphasis on colorectal cell lines.