Translation. Region: Russian Federation –
Source: Peoples'Friendship University of Russia
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Enar Dzhumaniyazova, an assistant in the Department of Histology, Cytology, and Embryology at the RUDN Medical Institute and a research fellow at the Research Institute of Molecular and Cellular Medicine, successfully defended her dissertation and became a candidate of medical sciences in two specialties: Cell Biology and Oncology and Radiation Therapy.
Enar Denisovna's dissertation, "A Study of the Cellular Composition and Molecular Signatures of Head and Neck Squamous Cell Carcinoma Before and After Proton Therapy," was conducted under the supervision of Associate Professors Polina Vishnyakova and Konstantin Gordon. The scientist focused on radiation-induced tissue responses in the peritumoral region of head and neck squamous cell carcinoma.
The researcher presented the results of a transcriptome analysis of tumor cells and peritumoral tissue cells before and after proton beam irradiation and described changes in the activity of signaling cascades. The study identified differentially expressed genes KR1, KR6B, and KR16—markers of response to proton therapy.
"I dreamed of research at the intersection of clinical and fundamental medicine, which is why this work turned out to be so scientifically intensive and interesting. I am incredibly grateful to Professor Timur Khaisamudinovich Fatkhutdinov for helping me realize my dream. It was he who invited me to study cell biology as an undergraduate, and then to graduate school. It was he who introduced me to my wonderful and talented supervisors, Polina Aleksandrovna and Konstantin Borisovich, as well as his research team. It is a tremendous honor for me to work under the guidance of such eminent scientists," says Enar Dzhumaniyazova.
About the essence of the study
According to Enar Denisovna, squamous cell carcinoma of the head and neck is the sixth most common malignancy worldwide, characterized by frequent recurrences and a relatively low five-year survival rate. In recent years, there has been a trend toward increasing incidence among young people, lending social significance to the study.
"The primary radiation therapy method used in routine practice is photon therapy. Improvements to this method have significantly increased the precision and effectiveness of radiation delivery. However, this dosimetric gain has led to an increase in the frequency and severity of radiation-related complications. This necessitates the urgent search for an optimal radiation therapy option to improve treatment outcomes and patient quality of life," says Enar Dzhumaniyazova.
According to the scientist, proton therapy is the most promising approach to solving this problem. Due to its physical properties, it allows for reduced radiation doses to surrounding tissues, thereby improving treatment outcomes by reducing the risk of radiation-related complications. However, the lack of fundamental research into the radiobiological effects of proton therapy prevents its introduction into routine clinical practice. Enard emphasizes that the relevance of the study is dictated by the high prevalence of squamous cell carcinoma of the head and neck and its aggressive course, as well as the emerging trend toward personalized antitumor treatment. The study comprehensively examined tumor tissue and the peritumoral tissue (surrounding the tumor), which is considered a source of recurrence. It also describes the biological effects of proton therapy at the cellular and transcriptomic levels.
Practical value of the work
The results obtained by Enar are of fundamental value, as they describe for the first time the response to proton therapy in peritumoral tissue of head and neck squamous cell carcinoma. The practical value lies in the identification of differentially expressed genes.
"These genes act as predictors (parameters) of response to proton therapy and could serve as the basis for the development of a diagnostic test system to personalize antitumor therapy and reduce the burden on proton therapy departments. Given the high cost of proton systems and their relatively low availability, the identified biomarkers are of significant importance for practical medicine," says Enar Dzhumaniyazova.
The researcher clarifies that the results of transcriptome analysis yielded a list of genes whose expression significantly changed after proton therapy in tumor cells and peritumoral tissue. Subsequent enrichment analysis of these genes helped identify numerous signaling cascades that were activated or suppressed after proton irradiation. These data reveal the mechanisms by which tumor cells and peritumoral cells respond or adapt to this type of treatment. To evaluate the clinical effects of proton therapy, patients were divided into two groups: those who responded to treatment and those who remained resistant. Comparison of the transcriptome profiles of both groups revealed differential molecular genetic signatures in peritumoral tissue cells. According to the data obtained, increased expression of the KR1, KR6B, and KR16 genes is associated with a poor patient response to proton therapy, while their decreased expression is associated with a good response. In the latter case, proton therapy would be justified. Regarding the difficulties on the path to her defense, Enar Denisovna admits that working on her dissertation was interesting, and the difficulties were easily overcome: scientific inspiration triumphed over fatigue again and again.
"Surprisingly, the hardest part was the last few days of preparation for the defense. Then, organizational difficulties compounded the department's administrative workload. Mentally, I felt incredibly stressed, perhaps more than I've ever felt in my life," says Enar Dzhumaniyazova.
According to the scientist, a few days before the defense, when her supervisor Polina Aleksandrovna Vishnyakova and Irina Vladimirovna Arutyunyan were listening to her, she could hardly pull herself together and deliver her report properly—mental exhaustion had taken its toll.
"But I knew how much effort had been invested in me and my work by Polina Alexandrovna, Professor Timur Khaisamudinovich Fatkhudinov, Konstantin Borisovich, and Irina Vladimirovna—I simply couldn't let them down. I'm happy to be surrounded by wonderful people, and during those difficult days, Alena Gantsova and Yulia Stepanova came to help with the organization, and I received incredible support from Professor Valeria Vladimirovna Glinkina," Enar Dzhumaniyazova.
Enar Denisovna is delighted that her thesis defense was held at the highest level, and she saw rays of happiness and pride in the eyes of her immensely respected mentors. The response to her work, the positive feedback and recommendations from world-class scientists, and the sincere emotions of her senior colleagues—in her opinion, this was all worth the effort.
The researcher plans to develop this research and continue the project. The resulting biomarkers of response to proton therapy are to be verified in a larger patient sample. Ideally, this will lead to the development of a diagnostic test system that will help guide the appropriate treatment of patients with squamous cell carcinoma of the head and neck.
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