Quantification of the synergism between HER-targeted drugs with human blood serum and EGF

Finding the optimal combination of drugs for the effective inhibition of cancer cell growth is an extremely important task today, as the number of such drugs continues to grow. There are several approaches to determining the nature of drug interactions, allowing one to establish whether they are additive, synergis tic, or antagonistic. One such approach is described here, and it is demonstrated how to quantitatively meas ure the degree of interaction between two drugs. It is shown that human peripheral blood serum and EGF modulate the activity of HER2-targeted drugs in inhibiting the proliferation of HER2-positive BT474 and SK-BR-3 cells. We compared the effect of blood serum samples from breast cancer (BC) patients and healthy donors on the action of trastuzumab. Using the proposed method, it is possible to calculate the Combination Index (CI). For 17 serum samples from healthy donors, the mean CI was 0.396, while for 19 serum samples from patients with BC, the mean CI was 0.214. These results indicate a synergistic interaction between tras tuzumab and blood serum in both groups. We also found significant differences in CI values between healthy donors and breast cancer patients: blood serum samples from patients enhance the effect of trastuzumab to a greater extent.