Implementation of scientific, scientific-technical program within the framework of results-based budgeting according to the Contract No. 386 for 2024-2026 years from 01.10.2024

Creation and implementation of innovative methods for the treatment of oncological diseases

Relevance

One of the strategic directions of ensuring sustainable socio-economic development of the Republic of Kazakhstan is the preservation of health and labor capacity of the nation. In 2019, the economic losses due to premature death of the able-bodied population of Kazakhstan amounted to 5,483.6 billion tenge, with cancer occupying the third place among the causes of premature mortality, amounting to 572.8 billion tenge. Tracheal, bronchial and lung cancer leads among them with 2,120 cases, while stomach cancer and breast cancer are in second and third place, respectively, with 1,560 and 1,060 cases out of 3,1505 initially detected. In 2022, 13,501 people died in Kazakhstan, which is 68.76 per 100,000 population.

Gastric cancer is one of the most common oncologic pathologies, and peritoneal dissemination is one of the most unfavorable variants of progression and recurrence of this cancer. The standard of treatment for locally advanced gastric cancer is currently complex therapy, including systemic chemotherapy and surgery. However, this technique does not solve the problem of peritoneal carcinomatosis development. Therefore, it is planned to develop a domestic science-based technique and nozzle for an effective mode of intra-abdominal aerosol chemotherapy of complex treatment of gastric cancer.

Effective treatment of pleural tumors, such as malignant pleural mesothelioma and locally advanced lung cancer, is a challenging task. To date, there is no established standard treatment regimen for these diseases worldwide. Multimodal approaches such as hyperthermic intrapleural chemotherapy (HITOC) have been shown to prolong the overall survival of patients. Therefore, it is planned to introduce innovative technologies such as HITOC and develop a clinical protocol for application in domestic medicine based on our medical center.

Breast cancer is also a serious medical problem, and breast removal is considered the primary treatment. However, a traumatic operation can lead to the development of lymphostasis of the upper limb. Therefore, there is a need to develop and implement methods of breast reconstruction using domestic biomaterials and methods aimed at preventing lymphostasis.

The program also involves clinical testing of a highly effective immunomodulator of a new generation based on a combination of monosaccharides for use as a dietary supplement in the treatment, prevention and palliative therapy of oncological diseases of various localization. The drug is based on a mixture of three isomers of monosaccharides (manose, glucose, and fructose) in a strictly defined quantitative ratio in combination with sodium citrate. The composition of the combination of monosaccharides based on a mixture of hexose isomers and the method of synthesis, as well as the mode of its activation by electromagnetic radiation is the subject of KNOW HOW.

Immunomodulatory properties of a combination of monosaccharides (CM) were proved in experiments on mice with inoculated aggressive breast cancer tumor. It is established that the preparation of CM has antitumor activity leading to suppression of tumor growth, development of metastases and increase in life expectancy of animals with solid tumors. It has been shown that the use of CM in experiments on mice with grafted aggressive tumor promotes an increase in the functional activity of immunocompetent cells such as macrophages, T-cells and natural killer cells (NKC).

The pronounced immunomodulatory properties of CM-1 were confirmed when CM-1 was used as a dietary supplement as an additional therapy in combination with traditional cytostatics on doomed patients with advanced forms of cancer (lung cancer, pancreatic cancer, melonoma, etc.). On several dozens of patients were obtained positive effects characteristic of effective immunotherapy based on the use of expensive immunomodulator, expressed in reduced toxicity, improved quality and duration of life.

It is expected that this development will have a significant impact on the level of treatment of oncologic diseases in the country, as well as contribute to the strengthening of the national economy through the development of domestic production of medical drugs.

Aim: Creation and implementation of innovative methods of oncologic diseases treatment.

Program Objectives:

1. Creation and implementation of innovative intra-abdominal pressurized aerosol aerosol chemotherapy in the complex treatment of patients with locally advanced gastric cancer.
2. Creation and introduction of innovative intrapleural hyperthermic chemotherapy to the treatment of patients with primary and metastatic pleural lesions in the complex treatment of patients with tumor lesions of the pleura.
3. Creation and introduction of innovative technology of breast reconstruction with the use of domestic acellular xenogenic matrix.
4. To develop the method of breast reconstruction after radical operations with decellularized xenogeneic matrix in combination with lymphovenular anastomoses in breast cancer.
5. To create production of a new generation immunomodulatory drug based on pharmacopoeial monosaccharides in combination with sodium citrate and its introduction into medical practice for treatment, prevention, rehabilitation and palliative therapy of oncologic diseases of various nosologies, including breast cancer, melanoma, pancreatic cancer, small cell lung cancer.

Expected Program Outcomes.

Direct Results:

The program will result in the following outcomes:

1. An innovative model of intra-abdominal pressurized aerosol chemotherapy with the developed Nozzle in the complex treatment of patients with locally advanced gastric cancer and personalized indications for them were created and implemented.
2. Treatment efficacy of the developed method of intra-abdominal pressurized aerosol chemotherapy was evaluated in comparison with patients who will not receive this treatment method.
3. Innovative intrapleural hyperthermic chemotherapy was created and introduced to the treatment of patients with primary and metastatic pleural lesions in the complex treatment of patients with tumor lesions of the thoracic cavity organs.
4. Personalized indications for intrapleural hyperthermic chemotherapy after cytoreductive surgeries in patients with tumor lesion of pleura were developed.
5. The effectiveness of treatment of patients with primary and metastatic pleural lesions, after cytoreductive surgeries using the developed method of intrapleural pressurized aerosol chemotherapy has been evaluated in comparison with patients who will not be treated with pressurized aerosol chemotherapy.
6. The innovative technology of breast reconstruction with the use of domestic acellular xenogenic matrix has been created and implemented, with the development of the technique of operation of one-stage breast reconstruction after mastectomy with implant fixation with acellular xenogenic matrix.
7. The method of breast reconstruction after radical surgeries with decellularized xenogeneic matrix combined with lymphovascular anastomoses in breast cancer was developed.
8. Production of a new generation immunomodulatory drug based on monosaccharides in combination with sodium citrate was created and introduced into medical practice for treatment, prevention, rehabilitation and palliative therapy of oncologic diseases of various nosologies, including breast cancer, melanoma, pancreatic cancer, small cell lung cancer.

Result: The results of the program will be implemented in the clinical practice of oncology service and surgical departments. The results obtained by us will be used by a wide range of specialists, namely physicians, oncologists, radiologists, surgeons, molecular biologists, geneticists and others.

The results of the program will result in the publication of:

1) Up to 11 articles and (or) reviews in peer-reviewed scientific publications in the scientific direction of the program, included in the 1st, 2nd  quartile on impact factor in the Web of Science database and (or) having a percentile on CiteScore in the Scopus database not less than 50.

2) Up to 12 (twelve) articles in journals recommended by the Science and Higher Education Quality Assurance Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan.

3) Up to 1 (one) monograph or training manual in foreign and (or) Kazakhstani publishing houses recommended by the Scientific Council and (or) Scientific and Technical Council of the applicant's organization;

4) at least 4 patents in foreign patent offices (European, American, Japanese) or up to 4 foreign or international patents included in the Derwent Innovations Index database (Web of Science, Clarivate Analytics) or at least 7 intellectual property objects (patent; for applications in the field of information technologies - copyright certificate) registered in the National Institute of Intellectual Property of the Republic of Kazakhstan.

Program Manager                                                                                              Adylkhanov T.A.