Knocking out a target can improve effect of cancer drugs

Recently scientists find in the process of studying skin cancer, leukemia and other types of tumors that some anti-cancer drugs which block the Hedgehog signaling pathway also have great potential in terms of blocking tumor proliferation, and many anticancer drugs take this signaling pathway as a target. But according to some research using recombinant mouse proteins, some with the clinical use of drugs, people gradually found that some tumors become resistant to this.

A * STAR cellular and molecular biology researchers have discovered a new target - once the target was knocked out, it will remove the resistance of cells to Hedgehog signaling pathway drug and improve the therapeutic effect. The main director of the project Philip Ingham said, "Inhibiting the activity of the target protein can block the Hedgehog activity in cells. Then we can greatly reduce drug resistance of tumors by the combination therapy of several drugs."

Hedgehog signaling pathway plays an important role in the growth and differentiation of embryonic cells, but the elevation of its activity in adult tissue can easily cause cells to become cancerous. Currently, vismodegib and sonidegib are important cancer drugs aiming at Smoothened protein in the Hedgehog signaling pathway and are mainly used in skin cancer. To avoid resistance of these drugs, the drugs in the downstream of Smoothened protein are also under research and development. Ingham and his colleagues focus on the GRK2 protein. Through experiments on zebrafish model, they have fully understood the functions of in this protein.

In early stage of experiments, scientists silenced the gene and found a lot of changes in the Hedgehog signaling pathway. Ingham said, "Our study emphasizes the importance of the mutant allele, GRK2 protein phosphorylation by way of regulation of Hedgehog signaling activity path. But with further research, we feel GRK2 protein can link with other proteins and regulate backwards signaling pathway."

Research indicates that since the GRK2 protein won't directly interact with Hedgehog, there may be some side effects in the end. Flarebio provides high-quality recombinant proteins such as recombinant Cdh9 at competitive prices.