A miracle from the point of view of science
Knowledge of the molecular mechanisms of "miraculous recoveries" from cancer will help fight it
Oncological diseases remain one of the leading causes of death in the modern world. A lot of efforts are directed against them, not only by doctors, but also by scientists who are trying to find molecular "keys" to this group of diseases. Along the way, they often turn to the study of cancer-resistant animals in order to understand the mechanisms of resistance and reproduce them, creating anti-cancer therapy for humans. But you can look at the people themselves – those of them whose body gives a persistent and strong response to the treatment of cancer, which is considered incurable.
As part of the national Exceptional Responders Initiative project, which aims to study the biological basis of the body's unusually effective response to cancer treatment, researchers studied the medical histories and tumor samples of 111 patients suffering from various types of cancer who received standard chemotherapy. The work was conducted under the guidance of scientists from the National Institute of Oncology, a division of the US National Institutes of Health (NIH).
Article by Wheeler et al. Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment published in the journal Cancer Cell.
The scientists defined an unusually effective or exceptional response to therapy as lasting at least three times longer than the average, and such a patient as a person who had a partial or complete response to treatment, which is usually effective in less than 10% of such patients.
Most of the patients in this study had metastatic cancer, when cancer cells spread throughout the body and form secondary foci of tumor growth. At this stage, cancer is usually extremely poorly treated, but some people surprisingly stayed alive for many years after therapy. The phenomenon of "miraculous recoveries" from incurable cancer has been known for a long time, but it has not been possible to study the mechanisms underlying them for a long time. And only modern tools of molecular biology allowed us to begin to solve such riddles, as well as try to apply the knowledge gained in practice within the framework of the concept of precision oncology.
To analyze the tumor tissue of patients, the scientists examined mutations in tumor DNA, the level of DNA methylation and the level of RNA of different genes reflecting their activity, as well as the presence and number of different immune cells in the tumor microenvironment. About a quarter of patients were able to identify molecular features that could explain the strangely high effectiveness of treatment.
In some cases, the infiltration of the tumor by certain types of immune cells was detected, which apparently reflected the active work of the patient's immune system aimed at destroying the tumor.
There were also various genetic variations, including rare combinations of mutations that cause a phenomenon known as synthetic lethality, when a mutation in a tumor "helps" a drug to kill cancer cells. For example, the researchers identified mutations in the BRCA1/2 genes in two patients, which play an important role in the processes of DNA repair, regulation of cell division and maintenance of genome stability. Usually mutations in these genes increase the risk of cancer. But in this case, the mutations disrupted the tumor's ability to "repair" DNA in such a way that they increased the effectiveness of chemotherapy with platinum-based drugs that damage the DNA of cancer cells.
Such findings can potentially be used in the development of new effective anti-cancer drugs that will exploit similar vulnerabilities of cancer cells. For example, by examining the tumors of two patients treated with the DNA-damaging drug temozolomide, the researchers determined which two molecular DNA repair pathways needed to be inactivated simultaneously (as happened naturally in these patients) to achieve an effective response. The development of such a drug can make temozolomide treatment more effective.
In addition, the study emphasizes the importance of diagnosing the molecular features of each tumor, which can indicate the optimal treatment method for this patient.
Portal "Eternal youth" http://vechnayamolodost.ru