Researchers at the Institute of Cytology (INC) of the Russian Academy of Sciences were able to increase the effectiveness of rectal cancer cell therapy by 20% using chloroquine, a well-known antimalarial drug that has recently been found to be able to fight tumors. Previously, this drug was tried to be used to treat coronavirus, but it did not show the desired effect. In the case of tumors, the drug not only showed good results, but also turned out to be less toxic than standard chemotherapy. Doctors highly appreciate the results obtained by Russian researchers and are confident that the medicine will be in demand among patients.
Colorectal cancer is a disease characterized by the appearance of a tumor in the large intestine and rectum. Up to 1 million patients with this disease are registered annually in the world. Mostly it is diagnosed in people over 50 years of age; in recent years, patients with such a tumor have become “younger”.
At an advanced stage, this type of cancer is highly resistant to widely used chemotherapy drugs, which increases the risk of death. Therefore, scientific teams around the world are looking for drugs and therapy regimens that can cure this disease at different stages. Scientists from the Institute of Cytology of the Russian Academy of Sciences, subordinate to the Ministry of Education and Science, used chloroquine for these purposes. During the pandemic, they tried to treat the coronavirus, but it did not show the desired effect.
“We have developed a new treatment regimen for rectal cancer based on chloroquine. Today it is actively used by physicians as a drug against malaria. However, relatively recently, scientists have found that this medicine has antitumor properties. In addition, in therapy we used a compound called CL-43, which significantly increased the effectiveness of chloroquine. Experiments on tumor cells of the human rectum have shown the effectiveness of the proposed therapy,” Alina Nicotina, a researcher at the Laboratory of Cell Defense Mechanisms of the Institute of Scientific Centers of the Russian Academy of Sciences, told Izvestia.
The compound CL-43 belongs to cardenolides, a group of toxic substances, some of which can block the synthesis of heat shock proteins. Such proteins are found in cancer cells and can increase their resistance to chemotherapy. In 2018, scientists from the Institute of Research Center of the Russian Academy of Sciences showed that, unlike other similar substances, CL-43 has low toxicity, which means it can be considered as a potential antitumor agent.
Experiments on the use of new therapy were carried out on cell lines of human rectal cancer. The samples were provided by the Clinic of High Medical Technologies named after. N.I. Pirogov St. Petersburg State University. The scientists first found that these cell lines were resistant to standard chemotherapy compounds. Then they monitored in real time for several days how chloroquine acts on cancer cells and what effect CL-43 has on its medicinal properties. It turned out that the drug is able to destroy cancer cells at different stages of the disease, and its use in conjunction with CL-43 enhances this effect by 20%.
“Our proposed therapy confirms the effectiveness of chloroquine as an antitumor drug, and we have shown this on cell lines obtained from patients with different stages of cancer development. Its effectiveness is increased by CL-43, which means that during chemotherapy it is possible to reduce the dosage of drugs, which, in turn, will reduce the manifestations of side effects, ”explained Alina Nicotina.
Colon cancer is a fairly common pathology: the individual risk of its development reaches 5-6%. About 1 million new cases are diagnosed annually in the world, Roman Yevstratov, an oncologist at Guta Clinic, told Izvestia. According to him, the five-year survival rate for this disease is about 60% in developed countries and less than 40% in countries with limited resources.
Scheme for analysis of the level of heat shock protein Hsp70 and its localization in colon tumor cells. Source: Press Service of the Institute of Cytology of the Russian Academy of Sciences
“Based on the results of this work, it can be concluded that a certain mechanism leads to the efficient death of the patient's colon cancer cells that are resistant to standard anticancer drugs. The combination of CL-43 and chloroquine led to almost 100% death of the population of colorectal cancer cells of different stages, which indicates the potential use of this regimen in clinical practice, ”the specialist is sure.
It is noteworthy that tumor cultures with established drug resistance to standard anticancer drugs were used for the study.“The results of the study are very encouraging, since rectal cancer is one of the most resistant to chemotherapy localizations. Chloroquine has previously been considered as an antitumor agent, but its effectiveness was insufficient, and toxicity in large doses was high. That is why the research conducted at the Institute of Scientific Centers of the Russian Academy of Sciences is of particular interest. Nevertheless, before considering such a combination as a possible way to treat patients, a lot of research is required, ”an oncologist, head of the department of antitumor drug therapy at the Clinical Center of Sechenov University Anastasia Fatyanova, told Izvestia.
The development of a new treatment regimen is currently underway. In the long term, scientists will be engaged in its introduction into wide medical practice, but this will require many years of preclinical trials. The project was supported by the Russian Science Foundation. The results of the study are published in the scientific journal Pharmaceuticals.
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