Growth and differentiation of cells including cancer cells have higher requirement in metabolic elements, because they have to produce new proteins, membranes and nucleic acids. Drugs that can interfere with cell metabolism and biosynthesis of the polymer are able to trigger different types of cellular stress signaling pathways, such as the involved stress protein toxicity. Then, the accumulation of unfolded proteins in the endoplasmic reticulum might cause pressure.
As is known, cells can correspond to the overall toxicity of pressure and then might produce pressure, temperature, oxidation and endoplasmic reticulum nutritional deficiency. The overall pressure of cells could suppress the larger part of protein translation, most of which has been regulated by transcription factor ATF4. In fact, sustained protein toxic stress can lead to cell death.
On one hand, the ONC201 has been seen as an important element in modern scientific research, just like tripeptide-10 citrulline. It’s reported that a new drug is already in clinical trials. Actually, in hematological and solid cancers, cell pressure can be the cause for cell death. In terms of solid tumors, the expression of receptors and the ligand gene encoding could be increased to a certain degree, which might inhibit the growth of lymphoma and leukemia cells in promoting kinase complex mTORC1. Apoptosis induced by ONC201 does not demand the tumor suppressor and transcription factor activity of p53.
While on the other hand, HER2-positive and endoplasmic reticulum can also play a significant role in such study. One common way to adapt the cell ER stress is to increase the process known as the endoplasmic reticulum associated degradation. The process can transporter cells out of the endoplasmic reticulum and be degraded as a target of proteasome. Researchers found that growth receptor ( HER2-positive ) of breast cancer cells can increase the signaling pathway of ER stress, as well as the associated degradation in endoplasmic reticulum. Because HER2’s signaling promotes protein synthesis, when cells encounter severe toxic stres, associated degradation of endoplasmic reticulum might be blocked.
In fact, recent studies not only emphasize the importance of being able to kill cancer cells or prevent proliferation of the compound, but also let everyone know how the cells work to identify a particular treatment that cancer patients most likely to respond to. Using a molecular to understand examples associated with signaling pathway of cellular stress may affect the development of new treatments, as well as more effective combination therapies.