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

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 IC₅₀ 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 IC₅₀ 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 GI₁₀₀. Additionally, the GR₁₀₀ allows different cell populations to be calibrated on the same basis when multiple experimental results are compared.

Conclusion

Since the GR₁₀₀ has properties that indicate the efficiency of anti-cancer drugs, both the efficacy and GR₁₀₀ of a particular anti-cancer drug can be used to effectively assess the resistance.