Hebrew University researchers cracked the mechanism of a new anti-cancer drug that shows more anti-cancer activity and no signs of toxicity * Pre-clinical research led by Hebrew University researchers, Prof. Idit Tshuva and Dr. Yuval Tabah, opens the door to modern chemotherapy based on molecules containing a center Titanium-type metallic that operate in a unique and effective mechanism
Chemotherapy is the first line of aggressive drug treatment, which broadly and effectively kills cancer cells of various types. The main disadvantage of chemotherapy is some damage to normal cells as well, and this is where the severe side effects of the drug come from. The side effects can over time cause damage to the patient and are the main factor that prevents the continuation of the effective chemotherapy treatment. Identifying a drug with broad anti-cancer activity on the one hand and minimal toxicity to the normal cells in the patient's body is the ultimate goal.
Today, over fifty percent of cancer patients in the world receive chemotherapies based on platinum, which has severe side effects. Prof. Idit Tshuva from the Institute of Chemistry at the Hebrew University has been developing in recent years innovative molecules for cancer treatment, based on the titanium atom. Titanium is a metal that is more friendly to the human body and is used today in a variety of everyday products, from Ekamoly for children to orthopedic implants. The use of titanium has become popular due to its being a metal that is not toxic to biological systems, and on the other hand provides mechanical strength. "Titanium is not a toxic metal and yet it apparently kills cancer cells specifically. Therefore, it will have fewer side effects than existing drugs. However, the compounds that have been developed to date were not stable enough, and therefore were not effective either," Prof. Tshuva previously told about her research on the subject. As part of her research, Prof. Tshuva developed a potential and promising drug based on titanium that is in pre-clinical research (which has long been registered as a patent in the USA). In a new study conducted by Prof. Tshuva together with Dr. Yuval Tabah from the Faculty of Medicine at the Hebrew University, and published in the journal iscience from the well-regarded scientific magazine Cell, the mechanism of action of this drug was explained.
In a genomic study that took about six years, the mechanism of action of the new drug was investigated in depth, and the findings were a milestone for them in understanding the anti-cancer activity. The researchers discovered that this drug works by damaging an important mechanism found in most cells called the 'endoplasmic reticulum'. The endoplasmic reticulum is important in the quality control of the folding, processing and modification of the proteins in the cell and it is also active in the synthesis of lipids and detoxification. In fact, the cancer cells that have undergone many genetic changes are more sensitive to manipulations on the endoplasmic reticulum, and the new drug knows how to take advantage of this. Another important conclusion that emerges from the article is that the mechanism of action of the titanium-based drug is different from that of the platinum compounds and does not work by binding to DNA, and that the mechanism allows for a wider treatment range and new combinations with drugs that work by other mechanisms.
Although the road to the approval of the new drug is still long, understanding its mechanism of action is a significant step towards the transition of the drug to clinical trials in humans. It is worth noting that the newly discovered findings are the result of combining research works by researchers from different fields. The chemists in this work opened the molecule, characterized it and its anti-cancer activity, the genomics and big data people characterized the genetic changes in the cells exposed to the drug and yielded the mechanistic information, and the biologists confirmed the findings with direct biological measurements. Dr. Tabah concludes: "This multidisciplinary study managed to reveal a mechanism of great potential importance in the development of new chemotherapy drugs based on titanium. In addition, this discovery is a significant step towards the application of titanium complexes in clinics."
Among others, Dr. Maya Miller and two medical and research students Maya Brown and Anna Malol participated in the study.
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