In both in vitro proliferation assays and in xenografted tumors, G12V containing SW48 cells were found to be completely unresponsive to Erbitux. However, G13D containing SW48 cells, along with the parental WT SW48 cells, were highly responsive to Erbitux. This experimental data was unambiguous, showing clearly that G13D mutations do not impart resistance to Erbitux therapy in these patient-relevant disease models. Bardelli and colleagues were thus prompted to subsequently perform a new and larger retrospective sequence analysis on colon cancer patient tumor samples for their K-Ras mutational status and compare this with their known clinical response data to Erbitux.
This patient study demonstrated a clear concordance with the X-Man disease model data and confirmed that G13D patients are benefitting from anti-EGFR therapy. Prospective clinical trials will need to be performed to confirm this suspicion and, if conclusive, may lead to a further refinement in the rules for prescribing EGFR-targeted therapies in colon cancer.