Abstract: The present invention provides, for the first time, the finding that organic cation transporters (OCTs) are major determinants of the anticancer activity of platinum-based drugs such as oxaliplatin, and therefore have clinical significance for selecting oxaliplatin as the preferred therapy for a cancer that expresses one or more OCTs, such as colorectal cancer or liver cancer. In addition, the OCT genotype can also be used to predict oxaliplatin response or to select therapy. The present invention also provides methods of treating or inhibiting cancers that expresses one or more OCTs by administering a therapeutically effective amount of a platinum-based drug such as an oxaliplatin analog having an organic non-leaving group with an increased size. The present invention further provides methods of sensitizing a therapy resistant cancer to a platinum-based drug such as oxaliplatin by administering a therapeutically effective amount of a nucleic acid encoding an OCT.