Prospective pharmacological methodology for establishing and evaluating anti-cancer drug resistant cell lines

Background Cell lines are often used to assess the resistance of anticancer drugs when in vivo analysis is not possible. However, the process for establishing anti-cancer drug resistance in cell cultures in vitro and the subsequent method of then evaluating resistance are not clearly established. Traditionally, the IC.sub.50 is the most commonly used indicator of resistance evaluation but it cannot represent the effectiveness of anti-cancer drugs in a clinical setting and lacks reliability because it is heavily affected by the cell doubling time. Hence, new indicators that can evaluate anti-cancer drug resistance are needed. Methods A novel resistance evaluation methodology was validated in this present study by establishing sunitinib resistance in renal cell carcinoma cells and assessing the cross-resistance of five different anti-cancer drugs. Results It was confirmed in this present study that the IC.sub.50 does not reflect the cell proliferation rates in a way that represents anti-cancer drug resistance. An alternative indicator that can also be clinically meaningful when using in vitro cell line systems is GI.sub.100. Additionally, the GR.sub.100 allows different cell populations to be calibrated on the same basis when multiple experimental results are compared. Conclusion Since the GR.sub.100 has properties that indicate the efficiency of anti-cancer drugs, both the efficacy and GR.sub.100 of a particular anti-cancer drug can be used to effectively assess the resistance. Keywords: Renal cell carcinoma, Sunitinib, Drug resistance, Cross-resistance, IC.sub.50, GR.sub.100