PROBLEM AND PERSPECTIVE TO IMPROVE MOLECULAR TESTING TO CHOOSE APPROPRIATE TARGET THERAPY
In the last decade, molecularly-targeted therapy is the most intensively developing treatment modalities in oncology. The main targets for this therapy are many elements of apoptosis signaling pathways and cell cycle regulation, the damage of which is associated with a malignant growth. One of the a...
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| Format: | Article |
| Language: | Russian |
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Russian Academy of Sciences, Tomsk National Research Medical Center
2016-02-01
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| Series: | Сибирский онкологический журнал |
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| Online Access: | https://www.siboncoj.ru/jour/article/view/32 |
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| author | P. A. Gervas N. V. Litviakov N. O. Popova A. Yu. Dobrodeev A. S. Tarasova E. L. Yumov F. G. Ivanova O. V. Cheremisina S. G. Afanasyev V. E. Goldberg N. V. Cherdyntseva |
| author_facet | P. A. Gervas N. V. Litviakov N. O. Popova A. Yu. Dobrodeev A. S. Tarasova E. L. Yumov F. G. Ivanova O. V. Cheremisina S. G. Afanasyev V. E. Goldberg N. V. Cherdyntseva |
| author_sort | P. A. Gervas |
| collection | DOAJ |
| description | In the last decade, molecularly-targeted therapy is the most intensively developing treatment modalities in oncology. The main targets for this therapy are many elements of apoptosis signaling pathways and cell cycle regulation, the damage of which is associated with a malignant growth. One of the available molecular targets is the epidermal growth factor receptor (EGFR), which activation occurs in lung cancer, colorectal cancer, squamous cell carcinoma of the head and neck , breast cancer, melanomas, etc. To block oncogenic EGFR signaling, target drug as small molecule tyrosine kinase inhibitors, peptide associated cytotoxins and antiEGFR monoclonal antibodies were created. However, there are a number of studies (FLEX, SATURN, INTEREST, IPASS), where the expected and observed clinical cure rates of target drugs are not the same, including primary goal - increasing time to tumor progression. As the cause of inconsistency of treatment results may be lack the selection of patients with the additional molecular damages (mutations or genetic polymorphisms), providing the sensitivity and /or resistance to therapeutic agent. The most important reason for discrepancy between the real and the expected treatment effect of target drugs is the phenomenon of intratumoral heterogeneity, that is manifested as coexist of cells with different biological properties, due to genetic, epigenetic, phenotypic peculiarities of tumor clones within the tumor. Search for new driver targets and the creation of drugs directed against them, development of multitarget approach are perspective to improve the effectiveness of targeted therapy. In addition, it is important to use molecular testing to monitor the treatment efficacy, because therapy can drive the tumor clonal evolution, leading to the emergence of resistant cell clones. |
| format | Article |
| id | doaj-art-a42cd8b6f05f4a57893a9014cc834738 |
| institution | DOAJ |
| issn | 1814-4861 2312-3168 |
| language | Russian |
| publishDate | 2016-02-01 |
| publisher | Russian Academy of Sciences, Tomsk National Research Medical Center |
| record_format | Article |
| series | Сибирский онкологический журнал |
| spelling | doaj-art-a42cd8b6f05f4a57893a9014cc8347382025-08-20T03:18:20ZrusRussian Academy of Sciences, Tomsk National Research Medical CenterСибирский онкологический журнал1814-48612312-31682016-02-0102465532PROBLEM AND PERSPECTIVE TO IMPROVE MOLECULAR TESTING TO CHOOSE APPROPRIATE TARGET THERAPYP. A. Gervas0N. V. Litviakov1N. O. Popova2A. Yu. Dobrodeev3A. S. Tarasova4E. L. Yumov5F. G. Ivanova6O. V. Cheremisina7S. G. Afanasyev8V. E. Goldberg9N. V. Cherdyntseva10Cancer Research Institute, Siberian Branch of the RAMS, TomskCancer Research Institute, Siberian Branch of the RAMS, Tomsk National Research Tomsk State University, TomskCancer Research Institute, Siberian Branch of the RAMS, TomskCancer Research Institute, Siberian Branch of the RAMS, TomskCancer Research Institute, Siberian Branch of the RAMS, TomskCancer Research Institute, Siberian Branch of the RAMS, TomskYakutskRepublic Oncologic Dispensary, Yakutsk, Sakha RepublicCancer Research Institute, Siberian Branch of the RAMS, TomskCancer Research Institute, Siberian Branch of the RAMS, TomskCancer Research Institute, Siberian Branch of the RAMS, TomskCancer Research Institute, Siberian Branch of the RAMS, Tomsk Siberian State Medical University, Tomsk National Research Tomsk State University, TomskIn the last decade, molecularly-targeted therapy is the most intensively developing treatment modalities in oncology. The main targets for this therapy are many elements of apoptosis signaling pathways and cell cycle regulation, the damage of which is associated with a malignant growth. One of the available molecular targets is the epidermal growth factor receptor (EGFR), which activation occurs in lung cancer, colorectal cancer, squamous cell carcinoma of the head and neck , breast cancer, melanomas, etc. To block oncogenic EGFR signaling, target drug as small molecule tyrosine kinase inhibitors, peptide associated cytotoxins and antiEGFR monoclonal antibodies were created. However, there are a number of studies (FLEX, SATURN, INTEREST, IPASS), where the expected and observed clinical cure rates of target drugs are not the same, including primary goal - increasing time to tumor progression. As the cause of inconsistency of treatment results may be lack the selection of patients with the additional molecular damages (mutations or genetic polymorphisms), providing the sensitivity and /or resistance to therapeutic agent. The most important reason for discrepancy between the real and the expected treatment effect of target drugs is the phenomenon of intratumoral heterogeneity, that is manifested as coexist of cells with different biological properties, due to genetic, epigenetic, phenotypic peculiarities of tumor clones within the tumor. Search for new driver targets and the creation of drugs directed against them, development of multitarget approach are perspective to improve the effectiveness of targeted therapy. In addition, it is important to use molecular testing to monitor the treatment efficacy, because therapy can drive the tumor clonal evolution, leading to the emergence of resistant cell clones.https://www.siboncoj.ru/jour/article/view/32epidermal growth factor receptor (egfr)molecular testingtarget therapyintratumor heterogeneity |
| spellingShingle | P. A. Gervas N. V. Litviakov N. O. Popova A. Yu. Dobrodeev A. S. Tarasova E. L. Yumov F. G. Ivanova O. V. Cheremisina S. G. Afanasyev V. E. Goldberg N. V. Cherdyntseva PROBLEM AND PERSPECTIVE TO IMPROVE MOLECULAR TESTING TO CHOOSE APPROPRIATE TARGET THERAPY Сибирский онкологический журнал epidermal growth factor receptor (egfr) molecular testing target therapy intratumor heterogeneity |
| title | PROBLEM AND PERSPECTIVE TO IMPROVE MOLECULAR TESTING TO CHOOSE APPROPRIATE TARGET THERAPY |
| title_full | PROBLEM AND PERSPECTIVE TO IMPROVE MOLECULAR TESTING TO CHOOSE APPROPRIATE TARGET THERAPY |
| title_fullStr | PROBLEM AND PERSPECTIVE TO IMPROVE MOLECULAR TESTING TO CHOOSE APPROPRIATE TARGET THERAPY |
| title_full_unstemmed | PROBLEM AND PERSPECTIVE TO IMPROVE MOLECULAR TESTING TO CHOOSE APPROPRIATE TARGET THERAPY |
| title_short | PROBLEM AND PERSPECTIVE TO IMPROVE MOLECULAR TESTING TO CHOOSE APPROPRIATE TARGET THERAPY |
| title_sort | problem and perspective to improve molecular testing to choose appropriate target therapy |
| topic | epidermal growth factor receptor (egfr) molecular testing target therapy intratumor heterogeneity |
| url | https://www.siboncoj.ru/jour/article/view/32 |
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