These sensitivity differences may be explained either by previous systemic chemotherapy for metastatic disease or by observations that CTCs from 35% of patients exhibited significant ERCC1 and GST over-expression (> 10%), involved in resistance to platinum compounds (Yu et al. 2009), CTCs from 34.8% of patients showed ≥ 5% TYMS, or DHFR, or SHMT1 expression, involved in resistance to 5-fluorouracil (Jensen et al. 2008; Di Paolo and Chu 2004), and CTCs from 77% of patients showed very high multi-drug resistance gene (MDR1) overexpression (≥ 65%). The gene discussed is DHFR; the disease is metastatic neoplasm.