Evaluating New Drugs against K-Ras4B/PDE6δ Using an in Vitro Approach

Abstract

Cancer represents the leading cause of global mortality worldwide. Recent estimates have shown that approximately 25% of all cancer types exhibiting KRAS mutations, making these mutations one of the most reported so far. Given the important role played by KRas during the progression of different tumors, the search for new therapeutic compounds that can reduce the adverse effects of this oncogene becomes evident. However, discovering effective anticancer compounds is a complex and time-consuming task. These compounds should ideally exhibit potent anticancer properties at low concentrations, with minimal impact on healthy cells. The validation of potential candidates involves several stages and methods, including in vitro techniques such as cell lines or primary cell cultures grown under 2D and 3D conditions. This chapter provides a comprehensive review of in vitro methods to support the effectiveness of two compounds, C14 and P8, specifically targeting mutant KRas as potential antitumor agents. Cytotoxicity assays were employed on breast and pancreatic cancer cell lines and primary cell cultures grown in 2D and 3D conditions to evaluate the effectiveness of these compounds. The use of multiple cell culture systems provides more pertinent data, enhancing our understanding and assessment of the potential benefits of new therapeutic molecules.