ΠΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π°Ρ K-ras, B-raf ΠΈ APC ΠΏΡΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΡ
![ΠΠΈΡΡΠ΅ΡΡΠ°ΡΠΈΡ: ΠΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π°Ρ
K-ras, B-raf ΠΈ APC ΠΏΡΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΡ](https://niscu.ru/work/5010294/cover.png)
Π ΡΠ²ΡΠ·ΠΈ Ρ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΊΠ°ΠΌΠΈ Π²ΡΡΠ΅ΠΏΠ΅ΡΠ΅ΡΠΈΡΠ»Π΅Π½Π½ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π²ΠΎΠ·Π½ΠΈΠΊΠ°Π΅Ρ Π·Π°Π΄Π°ΡΠ° ΠΏΠΎΠΈΡΠΊΠ° Π½ΠΎΠ²ΡΡ , Π±ΠΎΠ»Π΅Π΅ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΡΡ ΠΈ Π½Π°Π΄Π΅ΠΆΠ½ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΈ ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³Π° ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. Π ΡΠΈΡΠ»Ρ ΡΠ°ΠΊΠΈΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΎΡΠ½ΠΎΡΠΈΡΡΡ Π½ΠΎΠ²ΠΎΠ΅ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ Π² ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΉ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½Π΅ — ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠ°Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ°. Π ΠΎΡΠ»ΠΈΡΠΈΠ΅ ΠΎΡ ΠΈΠΌΠΌΡΠ½ΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ ΠΎΠ½ΠΊΠΎΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ², ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΎΠ½ΠΊΠΎΠΌΠ°ΡΠΊΠ΅ΡΡ ΠΎΠ±ΡΡΠ½ΠΎ ΡΠ²Π»ΡΡΡΡΡ ΠΌΡΡΠ°Π½ΡΠ½ΡΠΌΠΈ… Π§ΠΈΡΠ°ΡΡ Π΅ΡΡ >
- Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- ΠΡΠ΄Π΅ΡΠΆΠΊΠ°
- ΠΠΈΡΠ΅ΡΠ°ΡΡΡΠ°
- ΠΡΡΠ³ΠΈΠ΅ ΡΠ°Π±ΠΎΡΡ
- ΠΠΎΠΌΠΎΡΡ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈ
Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- ΠΠΠΠΠ 1. ΠΠΠΠΠ ΠΠΠ’ΠΠ ΠΠ’Π£Π Π«
- 1. 1. ΠΠ°ΡΡΡΠ΅Π½ΠΈΡ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠΉ ΡΡΠ°Π½ΡΠ΄ΡΠΊΡΠΈΠΈ ΠΊΠ°ΠΊ ΠΎΡΠ½ΠΎΠ²Π° Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΡΠΎΡΡΠ°
- 1. 2. RAS-ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΠΉ ΠΊΠ°ΡΠΊΠ°Π΄
- 1. 3. Ras: ΠΠΠΠ« ΠΈ ΠΠΠΠΠ
- 1. 3. 1. Ras-ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π°
- 1. 3. 2. Ras-Π³Π΅Π½Ρ ΠΈ Π±Π΅Π»ΠΊΠΈ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡΠ°ΡΡΠΈΡ
- 1. 3. 3. ΠΠΊΡΠΈΠ²Π°ΡΠΈΡ Ras-Π±Π΅Π»ΠΊΠΎΠ² ΠΈ ΡΡΠ°Π½ΡΡΠΎΡΠΌΠΈΡΡΡΡΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π°
- 1. 3. 4. Π Π°Π·Π»ΠΈΡΠΈΡ ΠΌΠ΅ΠΆΠ΄Ρ Π-, Π- ΠΈ N-Ras
- 1. 4. Π Π΅Π³ΡΠ»ΡΡΠΎΡΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ Ras-ΠΊΠ°ΡΠΊΠ°Π΄Π°
- 1. 5. ΠΠ΅Π»ΠΊΠΈ — ΠΌΠΈΡΠ΅Π½ΠΈ Ras
- 1. 6. Raf
- 1. 7. WNT-ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΠΉ ΠΊΠ°ΡΠΊΠ°Π΄
- 1. 8. ΠΠ°ΡΡΡΠ΅Π½ΠΈΡ Π² Π³Π΅Π½Π°Ρ
K-ras, Braf ΠΈ ΠΠ Π‘ ΠΏΡΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΡ
- 1. 8. 1. ΠΠ΅Π½ K-ras
- 1. 8. 2. ΠΠ΅Π½ B-raf
- 1. 8. 3. ΠΠ΅Π½ ΠΠ Π‘
- 1. 9. ΠΡΠΊΠ»Π΅ΠΈΠ½ΠΎΠ²ΡΠ΅ ΠΊΠΈΡΠ»ΠΎΡΡ ΠΊΡΠΎΠ²ΠΈ
- 1. 10. ΠΠ΄ΡΠ΅ΡΠ½Π°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡ (ΡΠ°ΡΠ³Π΅Ρ-ΡΠ΅ΡΠ°ΠΏΠΈΡ)
- ΠΠΠΠΠ 2. ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ
- 2. 1. Π Π°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΎΠ±ΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ Π»ΠΈΡ ΠΏΠΎ Π³ΡΡΠΏΠΏΠ°ΠΌ ΠΈ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ° ΠΈΠ·ΡΡΠ°Π΅ΠΌΡΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΎΠ±ΡΠ°Π·ΡΠΎΠ²
- 2. 2. ΠΠ°Π±ΠΎΡ ΠΊΡΠΎΠ²ΠΈ
- 2. 3. Π Π΅ΠΆΠΈΠΌΡ ΡΠ΅Π½ΡΡΠΈΡΡΠ³ΠΈΡΠΎΠ²Π°Π½ΠΈΡ
- 2. 4. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΠΠ ΠΈΠ· Π±ΠΈΠΎΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π°
- 2. 5. ΠΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½Π°Ρ ΡΠ΅ΠΏΠ½Π°Ρ ΡΠ΅Π°ΠΊΡΠΈΡ (ΠΠ¦Π ): 71 ΠΠΠ K-ras 72 ΠΠΠ B-raf 78 ΠΠΠΠΠ Π‘
- 2. 6. ΠΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π· Π² ΠΏΠΎΠ»ΠΈΠ°ΠΊΡΠΈΠ»Π°ΠΌΠΈΠ΄Π½ΠΎΠΌ Π³Π΅Π»Π΅ (ΠΠΠΠ)
- ΠΠΠΠΠ 3. Π ΠΠΠ£ΠΠ¬Π’ΠΠ’Π« ΠΠ‘Π‘ΠΠΠΠΠΠΠΠΠ―
- 3. 1. ΠΠ΅Π½ΠΠ-ras
- 3. 1. 1. ΠΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΡ ΡΡΠ»ΠΎΠ²ΠΈΠΉ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΎΠ±ΠΎΠ³Π°ΡΠ΅Π½Π½ΠΎΠΉ ΠΠ¦Π Π΄Π»Ρ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΠΌΡΡΠ°ΡΠΈΠΉ Π² 12-ΠΎΠΌ ΠΊΠΎΠ΄ΠΎΠ½Π΅ Π³Π΅Π½Π° K-ras
- 3. 1. 2. Π‘ΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΡΡΡ ΠΠ¦Π Π³Π΅Π½Π° K-ras Ρ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² 12-ΠΌ ΠΊΠΎΠ΄ΠΎΠ½Π΅ ΠΈ Ρ Π°ΡΠ°ΠΊΡΠ΅Ρ ΡΠΎΡΠΊΠΎΠ²ΡΡ ΠΌΡΡΠ°ΡΠΈΠΉ
- 3. 2. ΠΠ΅Π½ B-raf. 121 3.2.1 ΠΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΡ ΡΡΠ»ΠΎΠ²ΠΈΠΉ ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π·Π° ΠΏΡΠΈ ΠΎΡΠ΅Π½ΠΊΠ΅ Π΄Π΅ΡΠ΅ΠΊΡΠΎΠ² Π³Π΅Π½Π° B-raf
- 3. 3. ΠΠ΅Π½ ΠΠ Π‘
- 3. 3. 1. Π‘ΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΡΡΡ ΠΠ¦Π
- 3. 3. 2. ΠΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΡ ΡΡΠ»ΠΎΠ²ΠΈΠΉ ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π·Π°
- 3. 1. ΠΠ΅Π½ΠΠ-ras
ΠΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π°Ρ K-ras, B-raf ΠΈ APC ΠΏΡΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΡ (ΡΠ΅ΡΠ΅ΡΠ°Ρ, ΠΊΡΡΡΠΎΠ²Π°Ρ, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½Π°Ρ)
ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ ΡΠ΅ΠΌΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. Π ΡΡΡΠ°Π½Π°Ρ ΠΠ²ΡΠΎΠΏΡ ΠΈ Π‘Π΅Π²Π΅ΡΠ½ΠΎΠΉ ΠΠΌΠ΅ΡΠΈΠΊΠΈ ΡΠΌΠ΅ΡΡΠ½ΠΎΡΡΡ ΠΎΡ ΡΠ°ΠΊΠ° ΡΡΠΎΠΈΡ Π½Π° Π²ΡΠΎΡΠΎΠΌ ΠΌΠ΅ΡΡΠ΅ ΠΏΠΎΡΠ»Π΅ ΡΠΌΠ΅ΡΡΠ½ΠΎΡΡΠΈ ΠΎΡ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎ-ΡΠΎΡΡΠ΄ΠΈΡΡΡΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. Π’Π°ΠΊ, Π½Π°ΠΏΡΠΈΠΌΠ΅Ρ, ΡΠΎΠ»ΡΠΊΠΎ Π² Π‘Π¨Π ΡΠΈΡΠ»ΠΎ ΡΠΌΠ΅ΡΡΠ΅ΠΉ ΠΎΡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Π² 1994 Π³ΠΎΠ΄Ρ Π±ΡΠ»ΠΎ Π±ΠΎΠ»ΡΡΠ΅ Π½Π° 6% ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ 1970 Π³ΠΎΠ΄ΠΎΠΌ. ΠΠ·Π²Π΅ΡΡΠ½ΠΎ, ΡΡΠΎ ΠΏΡΠΈ Π²ΡΡΠ²Π»Π΅Π½ΠΈΠΈ ΠΎΠΏΡΡ ΠΎΠ»ΠΈ Π½Π° ΡΠ°Π½Π½ΠΈΡ ΡΡΠ°ΠΏΠ°Ρ ΡΠ°Π·Π²ΠΈΡΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΏΡΠΎΠ³Π½ΠΎΠ· ΡΠ²Π»ΡΠ΅ΡΡΡ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ Π±Π»Π°Π³ΠΎΠΏΡΠΈΡΡΠ½ΡΠΌ, Π²Π΅ΡΠΎΡΡΠ½ΠΎΡΡΡ ΠΈΠ·Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΌΠ½ΠΎΠ³ΠΈΡ ΡΠΎΡΠΌ ΡΠ°ΠΊΠ° ΠΏΡΠΈ ΡΡΠΎΠΌ Π²ΡΡΠΎΠΊΠ°, ΠΎΠ±ΡΠ΅ΠΌ ΠΎΠΏΠ΅ΡΠ°ΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΠΈΠ»ΠΈ ΠΈΠ½ΠΎΠ³ΠΎ Π»Π΅ΡΠ΅Π±Π½ΠΎΠ³ΠΎ Π²ΠΌΠ΅ΡΠ°ΡΠ΅Π»ΡΡΡΠ²Π° Π² ΡΠ°ΠΊΠΈΡ ΡΠ»ΡΡΠ°ΡΡ ΠΈΠΌΠ΅Π΅Ρ ΠΎΠ³ΡΠ°Π½ΠΈΡΠ΅Π½Π½ΡΡ ΡΡΠ°Π²ΠΌΠ°ΡΠΈΡΠ½ΠΎΡΡΡ Π΄Π»Ρ Π±ΠΎΠ»ΡΠ½ΠΎΠ³ΠΎ. ΠΡΠ»Π΅Π΄ΡΡΠ²ΠΈΠ΅ ΡΡΠΎΠ³ΠΎ ΡΠ°Π½Π½ΡΡ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ° Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ Π½ΠΎΠ²ΠΎΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠΉ, ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎ Π½Π° Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ ΡΡΠ°Π΄ΠΈΡΡ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΠΎΠ³ΠΎ ΠΏΡΠΎΡΠ΅ΡΡΠ°, ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΎΠ΄Π½ΠΎΠΉ ΠΈΠ· ΠΏΡΠΈΠΎΡΠΈΡΠ΅ΡΠ½ΡΡ Π·Π°Π΄Π°Ρ Π² ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΉ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΠΈ.
ΠΠ·Π²Π΅ΡΡΠ½ΠΎ, ΡΡΠΎ ΡΠ°ΠΊ — ΡΡΠΎ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΠΎΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅, Π²ΠΎΠ·Π½ΠΈΠΊΠ°ΡΡΠ΅Π΅ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΠ²Π½ΠΎΠ³ΠΎ Π½Π°ΠΊΠΎΠΏΠ»Π΅Π½ΠΈΡ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΠΉ ΠΈ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ Π² ΠΊΠ»Π΅ΡΠΊΠ΅. Π ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΠ΅ Π½Π΅ΡΠΊΠΎΠ»ΡΠΊΠΎ Π΄Π΅ΡΡΡΠΈΠ»Π΅ΡΠΈΠΉ Π½Π°ΡΠΊΠ° Π΄ΠΎΠ±ΠΈΠ»Π°ΡΡ Π±ΠΎΠ»ΡΡΠΈΡ ΡΡΠΏΠ΅Ρ ΠΎΠ² Π² ΡΠ°ΡΠΊΡΡΡΠΈΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΠΊΠ°Π½ΡΠ΅ΡΠΎΠ³Π΅Π½Π΅Π·Π°: Π±ΡΠ»ΠΎ ΠΎΠΏΠΈΡΠ°Π½ΠΎ ΠΎΠΊΠΎΠ»ΠΎ 200 Π³Π΅Π½ΠΎΠ² ΠΈ ΠΈΡ Π±Π΅Π»ΠΊΠΎΠ²ΡΡ ΠΏΡΠΎΠ΄ΡΠΊΡΠΎΠ², Π½Π°ΠΏΡΡΠΌΡΡ ΠΈΠ»ΠΈ ΠΊΠΎΡΠ²Π΅Π½Π½ΠΎ ΡΠ²ΡΠ·Π°Π½Π½ΡΡ Ρ Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΠ΅ΠΌ ΡΠ°ΠΊΠ°, ΠΎΠ΄Π½Π°ΠΊΠΎ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π² Π΄Π°Π½Π½ΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ Π½Π΅ Π²ΡΡ ΠΎΠ΄ΠΈΡ Π·Π° ΡΠ°ΠΌΠΊΠΈ Π°ΠΊΠ°Π΄Π΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ Π½Π°ΡΠΊΠΈ. Π ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΠ΅ Π³ΠΎΠ΄Ρ Π½Π°ΠΌΠ΅ΡΠΈΠ»Π°ΡΡ ΡΠ΅Π½Π΄Π΅Π½ΡΠΈΡ ΠΈΠ½ΡΠ΅Π³ΡΠ°ΡΠΈΠΈ ΡΡΠ½Π΄Π°ΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΡ ΠΈ ΠΏΡΠΈΠΊΠ»Π°Π΄Π½ΡΡ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΈ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠΈ Π΄Π»Ρ Π½ΡΠΆΠ΄ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½Ρ Π² Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ΅ ΠΈ Π²ΡΠ±ΠΎΡΠ΅ ΡΠ°ΠΊΡΠΈΠΊΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΌΠ½ΠΎΠ³ΠΈΡ Π½Π°ΡΡΠ½ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΡΠΈΠΌΠ΅Π½ΡΡΡΡΡ Π² ΠΊΠ»ΠΈΠ½ΠΈΠΊΠ΅, ΠΏΠΎΠ΄Ρ ΠΎΠ΄Ρ ΠΊ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ΅ ΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΌΠ½ΠΎΠ³ΠΈΡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Π±Π°Π·ΠΈΡΡΡΡΡΡ Π½Π° Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΡΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠΉ Π³Π΅Π½Π΅ΡΠΈΠΊΠΈ. Π Π°ΡΠΊΡΡΡΠΈΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΠΊΠ°Π½ΡΠ΅ΡΠΎΠ³Π΅Π½Π΅Π·Π° ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΡΠΎΠ·Π΄Π°Π²Π°ΡΡ Π½ΠΎΠ²ΡΠ΅ Π²ΡΡΠΎΠΊΠΎΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠ΅ Π½Π΅ΡΠΎΠΊΡΠΈΡΠ½ΡΠ΅ Π°Π³Π΅Π½ΡΡ, Π΄Π΅ΠΉΡΡΠ²ΡΡΡΠΈΠ΅ Π½Π΅ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²Π΅Π½Π½ΠΎ ΠΏΡΠΈ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΡΡ ΡΠ΅Ρ ΠΈΠ»ΠΈ ΠΈΠ½ΡΡ Π³Π΅Π½ΠΎΠ², ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π°ΡΡΠΈΡ ΡΡ ΠΏΡΠΈ Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΠΈ Π½Π΅ΠΎΠΏΠ»Π°Π·ΠΈΠΉ. Π’Π°ΠΊ, Π½Π°ΠΏΡΠΈΠΌΠ΅Ρ, ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Ρ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ, Π΄Π΅ΠΉΡΡΠ²ΡΡΡΠΈΠ΅ ΠΏΡΠΈ Π³ΠΈΠΏΠ΅ΡΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΊ ΡΠΏΠΈΠ΄Π΅ΡΠΌΠ°Π»ΡΠ½ΠΎΠΌΡ ΡΠΎΡΡΠΎΠ²ΠΎΠΌΡ ΡΠ°ΠΊΡΠΎΡΡ — ZD 1839 («Iressa»), OSI-774 (Tarceva) — ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΡ ΡΠΈΡΠΎΠ·ΠΈΠ½ΠΊΠΈΠ½Π°Π·Π½ΠΎΠ³ΠΎ Π΄ΠΎΠΌΠ΅Π½Π° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°. BAY 43 9006 — Π½ΠΎΠ²ΡΠΉ Π°Π³Π΅Π½Ρ, ΠΈΠ½Π³ΠΈΠ±ΠΈΡΡΡΡΠΈΠΉ Π±Π΅Π»ΠΊΠΎΠ²ΡΠΉ ΠΏΡΠΎΠ΄ΡΠΊΡ Π³Π΅Π½Π° B-raf, ΡΠ°ΡΡΠΎ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π°ΡΡΠ΅Π³ΠΎΡΡ ΠΏΡΠΈ ΠΌΠ΅Π»Π°Π½ΠΎΠΌΠ°Ρ ΠΈ ΠΏΠ°ΠΏΠΈΠ»Π»ΡΡΠ½ΡΡ ΠΎΠΏΡΡ ΠΎΠ»ΡΡ ΡΠΈΡΠΎΠ²ΠΈΠ΄Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ. Π’Π°ΠΊΠΆΠ΅ ΡΠΎΠ·Π΄Π°Π½Ρ ΠΈ ΠΏΡΠΎΡ ΠΎΠ΄ΡΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΡΠΏΡΡΠ°Π½ΠΈΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ, Π΄Π΅ΠΉΡΡΠ²ΡΡΡΠΈΠ΅ Π½Π° ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠ΅ ΡΠ°ΠΏΠ΅ΡΠΎΠ½Ρ — ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΡ Hsp90 (17AAG), Π±Π»ΠΎΠΊΠ°ΡΠΎΡΡ ΡΠΎΡΡΠΎΠ²ΡΡ ΡΠ°ΠΊΡΠΎΡΠΎΠ² ΡΠΎΡΡΠ΄ΠΈΡΡΠΎΠ³ΠΎ ΡΠ½Π΄ΠΎΡΠ΅Π»ΠΈΡ — Avastin, SU11248 ΠΈ ΠΌΠ½ΠΎΠ³ΠΈΠ΅ Π΄ΡΡΠ³ΠΈΠ΅ [1]. ΠΡΠΈ ΡΠ°ΠΊΠΎΠΌ ΠΏΠΎΠ΄Ρ ΠΎΠ΄Π΅ ΡΠ²Π΅Π»ΠΈΡΠΈΠ²Π°Π΅ΡΡΡ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΡΡΠ΅ΠΊΡ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΈ ΡΠΌΠ΅Π½ΡΡΠ°Π΅ΡΡΡ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΏΠΎΠ±ΠΎΡΠ½ΡΡ ΡΡΡΠ΅ΠΊΡΠΎΠ². ΠΠ»Ρ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΠ΅Π»Π΅Π²ΡΡ Π°Π³Π΅Π½ΡΠΎΠ² Π½Π΅ΠΎΠ±Ρ ΠΎΠ΄ΠΈΠΌΠΎ ΠΈΠΌΠ΅ΡΡ ΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΡ ΠΎ Π½Π°Π»ΠΈΡΠΈΠΈ Π΄Π΅ΡΠ΅ΠΊΡΠΎΠ², ΠΊΠΎΡΠΎΡΡΠ΅ Π΄Π°Π½Π½ΠΎΠ΅ ΡΡΠ΅Π΄ΡΡΠ²ΠΎ ΠΏΡΠΈΠ·Π²Π°Π½ΠΎ ΠΈΡΠΏΡΠ°Π²ΠΈΡΡ. ΠΡΠΎ ΡΡΠ΅Π±ΡΠ΅Ρ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠΈ Π½ΠΎΠ²ΡΡ , ΠΏΡΠΈΠΌΠ΅Π½ΠΈΠΌΡΡ Π² ΠΊΠ»ΠΈΠ½ΠΈΠΊΠ΅ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΈΡ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΌΡΡΠ°ΡΠΈΠΉ.
Π₯ΠΎΡΡ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½Π°Ρ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½Π° ΠΎΠ±Π»Π°Π΄Π°Π΅Ρ Π±ΠΎΠ»ΡΡΠΈΠΌ Π°ΡΡΠ΅Π½Π°Π»ΠΎΠΌ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠΉ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, ΡΠ°Π½Π½Π΅Π΅ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΈΠ΅ ΠΎΠΏΡΡ ΠΎΠ»Π΅ΠΉ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎ Π½Π΅ Π²ΡΠ΅Π³Π΄Π°. ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, ΠΌΠ½ΠΎΠ³ΠΈΠ΅ ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΠ΅" Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΡΠΎΡΠ΅Π΄ΡΡΡ ΠΈΠΌΠ΅ΡΡ ΠΈΠ½Π²Π°Π·ΠΈΠ²Π½ΡΠΉ Ρ Π°ΡΠ°ΠΊΡΠ΅Ρ.
ΠΠΌΠΌΡΠ½ΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ, Ρ ΠΎΡΡ ΠΈ Π½Π΅ ΠΈΠ½Π²Π°Π·ΠΈΠ²Π½Ρ ΠΈ ΠΈΠΌΠ΅ΡΡ ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π½Π΅Π²ΡΡΠΎΠΊΡΡ ΡΡΠΎΠΈΠΌΠΎΡΡΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Π°Π½Π°Π»ΠΈΠ·Π°, ΠΈΠΌΠ΅ΡΡ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΡΡ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ Π΄Π»Ρ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ Π½Π΅ΠΎΠΏΠ»Π°Π·ΠΈΠΈ Π½Π° ΡΠ°Π½Π½ΠΈΡ ΡΡΠ°Π΄ΠΈΡΡ . ΠΠ°ΠΆΠ½ΠΎ ΠΎΡΠΌΠ΅ΡΠΈΡΡ, ΡΡΠΎ ΠΈΠΌΠΌΡΠ½ΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΎΠ½ΠΊΠΎΠΌΠ°ΡΠΊΠ΅ΡΡ, ΠΊΠ°ΠΊ ΠΏΡΠ°Π²ΠΈΠ»ΠΎ, ΡΠ²Π»ΡΡΡΡΡ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΡΠΌΠΈ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠ°ΠΌΠΈ ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ. ΠΡΠΈ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ Π½ΠΎΠ²ΠΎΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡΡ ΡΠ²Π΅Π»ΠΈΡΠΈΠ²Π°Π΅ΡΡΡ ΠΈΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡ Π² ΠΊΡΠΎΠ²ΠΈ, Π½ΠΎ ΡΠ°ΠΊΠΎΠΉ ΡΡΡΠ΅ΠΊΡ ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ Π²ΡΠ·ΡΠ²Π°ΠΉ Π²ΠΎΡΠΏΠ°Π»ΠΈΡΠ΅Π»ΡΠ½ΡΠΌΠΈ ΠΏΡΠΎΡΠ΅ΡΡΠ°ΠΌΠΈ.
ΠΠ»Ρ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΈΡ Π΄ΠΈΠ°Π³Π½ΠΎΠ·Π° ΡΠ°ΡΡΠΎ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΡΡ Π³ΠΈΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΡΡ Π²Π΅ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ, Π΄Π»Ρ ΡΠ΅Π³ΠΎ ΠΏΡΠΈΠ±Π΅Π³Π°ΡΡ ΠΊ Π±ΠΈΠΎΠΏΡΠΈΠΈ. ΠΠ΅ΡΠΌΠΎΡΡΡ Π½Π° ΡΠΎ, ΡΡΠΎ Π±ΠΈΠΎΠΏΡΠΈΡ Π΄Π°Π΅Ρ ΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΡ ΠΎ ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ°Ρ , ΡΠ΅Π·ΡΠ»ΡΡΠ°Ρ Π΅Π΅ Π·Π°Π²ΠΈΡΠΈΡ ΠΎΡ ΡΠΎΡΠ½ΠΎΡΡΠΈ ΠΏΠΎΠΏΠ°Π΄Π°Π½ΠΈΡ Π² ΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΡΠΉ ΠΎΡΠ°Π³. ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, Π±ΠΈΠΎΠΏΡΠΈΡ ΡΡΠ°Π²ΠΌΠ°ΡΠΈΡΠ½Π° Π΄Π»Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ°.
Π ΡΠ²ΡΠ·ΠΈ Ρ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΊΠ°ΠΌΠΈ Π²ΡΡΠ΅ΠΏΠ΅ΡΠ΅ΡΠΈΡΠ»Π΅Π½Π½ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π²ΠΎΠ·Π½ΠΈΠΊΠ°Π΅Ρ Π·Π°Π΄Π°ΡΠ° ΠΏΠΎΠΈΡΠΊΠ° Π½ΠΎΠ²ΡΡ , Π±ΠΎΠ»Π΅Π΅ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΡΡ ΠΈ Π½Π°Π΄Π΅ΠΆΠ½ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΈ ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³Π° ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. Π ΡΠΈΡΠ»Ρ ΡΠ°ΠΊΠΈΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΎΡΠ½ΠΎΡΠΈΡΡΡ Π½ΠΎΠ²ΠΎΠ΅ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ Π² ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΉ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½Π΅ — ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠ°Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ°. Π ΠΎΡΠ»ΠΈΡΠΈΠ΅ ΠΎΡ ΠΈΠΌΠΌΡΠ½ΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ ΠΎΠ½ΠΊΠΎΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ², ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΎΠ½ΠΊΠΎΠΌΠ°ΡΠΊΠ΅ΡΡ ΠΎΠ±ΡΡΠ½ΠΎ ΡΠ²Π»ΡΡΡΡΡ ΠΌΡΡΠ°Π½ΡΠ½ΡΠΌΠΈ Π³Π΅Π½Π°ΠΌΠΈ ΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ ΠΎΠΆΠ΄Π΅Π½ΠΈΡ, ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ Π² ΠΊΠΎΡΠΎΡΡΡ ΠΈΠΌΠ΅ΡΡ ΠΊΠ°ΠΊ ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠΉ, ΡΠ°ΠΊ ΠΈ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠΉ Ρ Π°ΡΠ°ΠΊΡΠ΅Ρ. ΠΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΎΠ½ΠΊΠΎΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΎ Π½Π° ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ Π½ΡΠΊΠ»Π΅ΠΈΠ½ΠΎΠ²ΡΡ ΠΊΠΈΡΠ»ΠΎΡ ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ. Π€Π°ΠΊΡ ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΡ Π½ΡΠΊΠ»Π΅ΠΈΠ½ΠΎΠ²ΡΡ ΠΊΠΈΡΠ»ΠΎΡ Π² ΠΏΠ»Π°Π·ΠΌΠ΅ ΠΊΡΠΎΠ²ΠΈ Π±ΡΠ» ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ Π΅ΡΠ΅ Π² 1948 Π³ΠΎΠ΄Ρ [2]. ΠΡΠΈ Π±ΠΎΠ»Π΅Π΅ ΠΏΠΎΠ·Π΄Π½ΠΈΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡΡ ΡΠΎΡΡΠ°Π²Π° ΠΈ ΠΏΡΠΎΠΈΡΡ ΠΎΠΆΠ΄Π΅Π½ΠΈΡ Π½ΡΠΊΠ»Π΅ΠΈΠ½ΠΎΠ²ΡΡ ΠΊΠΈΡΠ»ΠΎΡ ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ Π±ΡΠ»ΠΎ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΎ, ΡΡΠΎ ΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΡΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ Π²ΡΠ΄Π΅Π»ΡΡΡ ΡΠ²ΠΎΡ ΠΠΠ Π² ΠΊΡΠΎΠ²ΠΎΡΠΎΠΊ [3], ΠΏΡΠΈΡΠ΅ΠΌ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΠΠΠ Π² ΠΏΠ»Π°Π·ΠΌΠ΅ ΠΊΡΠΎΠ²ΠΈ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΎΠ±ΡΡΠ½ΠΎ Π½Π°ΠΌΠ½ΠΎΠ³ΠΎ Π±ΠΎΠ»ΡΡΠ΅, ΡΠ΅ΠΌ Ρ Π·Π΄ΠΎΡΠΎΠ²ΡΡ [3,4].
ΠΡΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ ΠΠΠ ΠΈΠ· ΠΎΠΏΡΡ ΠΎΠ»ΠΈ ΠΈ ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ ΠΎΠ±Π½Π°ΡΡΠΆΠΈΠ²Π°Π΅ΠΌΡΠ΅ ΠΌΡΡΠ°ΡΠΈΠΈ Π² Π³Π΅Π½Π°Ρ -ΠΎΠ½ΠΊΠΎΠΌΠ°ΡΠΊΠ΅ΡΠ°Ρ ΠΈΠ΄Π΅Π½ΡΠΈΡΠ½Ρ, Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ ΠΏΡΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ ΠΠΠ ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ Π·Π΄ΠΎΡΠΎΠ²ΡΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² (Π½Π΅ ΠΈΠΌΠ΅ΡΡΠΈΡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π΄ΠΈΠ°Π³Π½ΠΎΠ·Π°) ΡΠ°ΠΊΠΈΠ΅ ΠΌΡΡΠ°ΡΠΈΠΈ Π½Π΅ Π²ΡΡΠ²Π»ΡΡΡΡΡ [5, 6]. ΠΡΡΡΡΡΡΠ²ΠΈΠ΅ Π² Π½ΠΎΡΠΌΠ΅ ΠΈ ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠ΅ ΠΏΡΠΈ ΡΠ°ΠΊΠ΅ Π² ΠΏΠ»Π°Π·ΠΌΠ΅ ΠΊΡΠΎΠ²ΠΈ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ Π³Π΅Π½ΠΎΠ² ΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ ΠΎΠΆΠ΄Π΅Π½ΠΈΡ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΏΡΠΈΠ½ΡΠΈΠΏΠΈΠ°Π»ΡΠ½ΡΠΌ ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ²ΠΎΠΌ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΎΠ½ΠΊΠΎΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΠΏΠ΅ΡΠ΅Π΄ ΠΈΠΌΠΌΡΠ½ΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ. ΠΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ²ΠΎΠΌ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈ Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠ°Ρ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² (Π² ΡΡΡΡΡΡ ΠΈ Π±ΠΎΠ»Π΅Π΅ ΡΠ°Π·).
ΠΠ·Π²Π΅ΡΡΠ½ΠΎ, ΡΡΠΎ Π½Π° ΠΏΡΡΠΈ ΡΡΠ°Π½ΡΡΠΎΡΠΌΠ°ΡΠΈΠΈ Π² ΠΊΠ»Π΅ΡΠΊΠ΅ ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ ΡΡΠ΄ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠΎΠ±ΡΡΠΈΠΉ, Π²Π΅Π΄ΡΡΠΈΡ ΠΊ Π½Π°ΡΡΡΠ΅Π½ΠΈΡ ΡΡΠ½ΠΊΡΠΈΠΉ Π³Π΅Π½ΠΎΠ², ΠΊΠΎΠ½ΡΡΠΎΠ»ΠΈΡΡΡΡΠΈΡ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΉ ΡΠΈΠΊΠ» ΠΈ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ ΡΠ΅Π»ΠΎΡΡΠ½ΠΎΡΡΠΈ Π³Π΅Π½ΠΎΠΌΠ°. Π’Π°ΠΊΠΈΠΌΠΈ ΡΠΎΠ±ΡΡΠΈΡΠΌΠΈ Π² ΠΊΠ»Π΅ΡΠΊΠ΅ ΡΠ²Π»ΡΡΡΡΡ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ (Π·Π°ΠΌΠ΅Π½Π° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΉ, Π΄Π΅Π»Π΅ΡΠΈΠΈ-ΠΈΠ½ΡΠ΅ΡΡΠΈΠΈ, ΡΠ΄Π²ΠΈΠ³ ΡΠ°ΠΌΠΊΠΈ ΡΡΠΈΡΡΠ²Π°Π½ΠΈΡ, Π°ΠΌΠΏΠ»ΠΈΡΠΈΠΊΠ°ΡΠΈΡ Π³Π΅Π½ΠΎΠ², ΡΠ΅ΡΠΈΠΏΡΠΎΠΊΠ½ΡΠ΅ ΠΈ Π½Π΅ΡΠ΅ΡΠΈΠΏΡΠΎΠΊΠ½ΡΠ΅ ΡΡΠ°Π½ΡΠ»ΠΎΠΊΠ°ΡΠΈΠΈ ΠΈ Π΄Ρ.) ΠΈΠ»ΠΈ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ (ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΡΠ°ΡΡΡΠ° ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΡ ΠΎΠ±Π»Π°ΡΡΠ΅ΠΉ Π³Π΅Π½ΠΎΠ²) Π½Π°ΡΡΡΠ΅Π½ΠΈΡ [7, 8]. Π‘Π»Π΅Π΄ΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ°ΠΊΠΈΡ ΡΠΎΠ±ΡΡΠΈΠΉ ΡΠ²Π»ΡΡΡΡΡ ΡΠ±ΠΎΠΈ Π² ΡΠ΅Π³ΡΠ»ΠΈΡΠΎΠ²ΠΊΠ΅ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠΊΠ»Π°, ΠΏΡΠΈ ΠΊΠΎΡΠΎΡΠΎΠΌ ΠΊΠ»Π΅ΡΠΊΠ° ΠΏΡΠΈΠΎΠ±ΡΠ΅ΡΠ°Π΅Ρ ΠΏΠΎΠ²ΡΡΠ΅Π½Π½ΡΠΉ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΡΠΉ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΠΏΠΎΡΠ΅ΡΡ ΠΊΠ»Π΅ΡΠΊΠΎΠΉ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²ΠΊΠΈ ΠΈ Π½Π΅ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ Π²ΡΠΏΠΎΠ»Π½ΡΡΡ ΡΠ²ΠΎΠΈ ΡΡΠ½ΠΊΡΠΈΠΈ Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ΅ΡΡΡΠ°ΡΠ° Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΡΠ°Π±ΠΈΠ»ΡΠ½ΠΎΡΡΠΈ, Π²Π΅Π΄ΡΡΠ°Ρ ΠΊ Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ΅ΠΌΡ Π½Π°ΠΊΠΎΠΏΠ»Π΅Π½ΠΈΡ ΠΌΡΡΠ°ΡΠΈΠΉ. ΠΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ Π²ΡΡΠ²ΠΈΡΡ ΡΠ°ΠΊΠΈΠ΅ ΠΌΡΡΠ°ΡΠΈΠΈ, ΠΊΠΎΠ³Π΄Π° ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΡΡΠ°Π½ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π²ΡΠΈΡ ΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ΅ ΠΈΡΡΠΈΡΠ»ΡΠ΅ΡΡΡ Π½Π΅ΡΠΊΠΎΠ»ΡΠΊΠΈΠΌΠΈ ΡΡΡΡΡΠ°ΠΌΠΈ, ΡΠΎ Π΅ΡΡΡ Π½Π° ΡΠ°ΠΌΡΡ ΡΠ°Π½Π½ΠΈΡ , Π΅ΡΠ΅ Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ ΡΡΠ°ΠΏΠ°Ρ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ.
Π¦Π΅Π»Ρ ΠΈ Π·Π°Π΄Π°ΡΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ
Π¦Π΅Π»ΡΡ Π½Π°ΡΡΠΎΡΡΠ΅ΠΉ ΡΠ°Π±ΠΎΡΡ ΡΠ²Π»ΡΠ»ΠΎΡΡ ΡΡΠΎΠ²Π΅ΡΡΠ΅Π½ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π°Π½Π°Π»ΠΈΠ·Π° Π³Π΅Π½ΠΎΠ² K-ras, B-raf ΠΈ ΠΠ Π‘ Π΄Π»Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ ΠΈΡ Π² Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ΅ ΠΈ ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³Π΅ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ.
ΠΠ»Ρ ΠΎΡΡΡΠ΅ΡΡΠ²Π»Π΅Π½ΠΈΡ ΡΠ΅Π»ΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π±ΡΠ»ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Ρ ΡΠ»Π΅Π΄ΡΡΡΠΈΠ΅ Π·Π°Π΄Π°ΡΠΈ:
1) Π°Π΄Π°ΠΏΡΠ°ΡΠΈΡ ΠΌΠ΅ΡΠΎΠ΄Π° ΠΎΠ±ΠΎΠ³Π°ΡΠ΅Π½Π½ΠΎΠΉ ΠΠ¦Π Π³Π΅Π½Π° K-ras Π΄Π»Ρ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΠΌΡΡΠ°ΡΠΈΠΉ ΡΡΠΎΠ³ΠΎ Π³Π΅Π½Π° Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΎΠ±ΡΠ°Π·ΡΠ°Ρ ;
2) ΠΎΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΡ ΡΡΠ»ΠΎΠ²ΠΈΠΉ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΠ¦Π ΠΈ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΡΠ΅Π³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° ΠΊΠΎΠ½ΡΠΎΡΠΌΠ°ΡΠΈΠΎΠ½Π½ΠΎΠ³ΠΎ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠ° ΠΎΠ΄Π½ΠΎΠ½ΠΈΡΠ΅Π²ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² (SSCP) Π΄Π»Ρ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ B-raf,.
3) ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ° ΠΏΡΠ°ΠΉΠΌΠ΅ΡΠΎΠ² ΠΈ ΠΏΠΎΠ΄Π±ΠΎΡ ΡΡΠ»ΠΎΠ²ΠΈΠΉ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΠ¦Π ΠΈ SSCP-Π°Π½Π°Π»ΠΈΠ·Π° Π΄Π»Ρ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ ΠΠ Π‘',.
4) ΠΎΡΠ΅Π½ΠΊΠ° ΠΏΡΠΈΠΌΠ΅Π½ΠΈΠΌΠΎΡΡΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΏΡΠΈΠ΅ΠΌΠΎΠ² ΠΊ Π°Π½Π°Π»ΠΈΠ·Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΎΠ±ΡΠ°Π·ΡΠΎΠ², Π²ΠΊΠ»ΡΡΠ°Ρ ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ, Π΄Π»Ρ ΠΌΠ°ΡΡΠΎΠ²ΠΎΠ³ΠΎ ΠΎΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ.
ΠΠ°ΡΡΠ½Π°Ρ Π½ΠΎΠ²ΠΈΠ·Π½Π° ΡΠ°Π±ΠΎΡΡ.
ΠΠ°ΡΡΠ½Π°Ρ Π½ΠΎΠ²ΠΈΠ·Π½Π° Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π·Π°ΠΊΠ»ΡΡΠ°Π΅ΡΡΡ Π²:
1) Π°Π΄Π°ΠΏΡΠ°ΡΠΈΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΎΠ½ΠΊΠΎΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ², ΠΈΠ·Π²Π΅ΡΡΠ½ΡΡ Π΄Π»Ρ ΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΡΡ ΡΠΊΠ°Π½Π΅ΠΉ, ΠΊ ΠΠΠ ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ, Π³Π΄Π΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡ ΠΠΠ Π² ΡΡΡΡΡΠΈ ΡΠ°Π· ΠΌΠ΅Π½ΡΡΠ΅, ΡΠ΅ΠΌ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡ ΠΠΠ ΠΈΠ· ΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΠΎΠ³ΠΎ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π° ΡΠΎΠ³ΠΎ ΠΆΠ΅ ΠΎΠ±ΡΡΠΌΠ°;
2) ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ΅ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ B-raf { 15-ΠΉ ΡΠΊΠ·ΠΎΠ½) Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΎΠ±ΡΠ°Π·ΡΠ°Ρ , Π²ΠΊΠ»ΡΡΠ°Ρ ΠΠΠ ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ, ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ SSCP-Π°Π½Π°Π»ΠΈΠ·Π°.
3) ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ΅ ΠΏΡΠ°ΠΉΠΌΠ΅ΡΠΎΠ² ΠΈ ΠΏΠΎΠ΄Π±ΠΎΡΠ° ΡΡΠ»ΠΎΠ²ΠΈΠΉ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ ΠΠ Π‘ (15-ΠΉ ΡΠΊΠ·ΠΎΠ½, ΡΠ°ΠΉΠΎΠ½ 1309-Π³ΠΎ ΠΊΠΎΠ΄ΠΎΠ½Π°) Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΎΠ±ΡΠ°Π·ΡΠ°Ρ , Π²ΠΊΠ»ΡΡΠ°Ρ ΠΠΠ ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ, ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ SSCP-Π°Π½Π°Π»ΠΈΠ·Π°.
ΠΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠ°Ρ Π·Π½Π°ΡΠΈΠΌΠΎΡΡΡ.
1) ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ Π°Π½Π°Π»ΠΈΠ·Π° Π³Π΅Π½ΠΎΠ² K-ras, B-raf ΠΈ ΠΠ Π‘ Π°Π΄Π°ΠΏΡΠΈΡΠΎΠ²Π°Π½Ρ ΠΊ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ Π² Π½Π°ΡΡΠ½ΠΎ-ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΡΠΊΠΈΡ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΈΡ ΡΡΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΡΡ ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠ΅Π½ΡΡΠ°Ρ . ΠΠ΅ΡΠΎΠ΄Ρ Π°Π½Π°Π»ΠΈΠ·Π° Π³Π΅Π½ΠΎΠ² K-ras ΠΈ B-raf Π²Π½Π΅Π΄ΡΠ΅Π½Ρ Π² ΡΠ°Π±ΠΎΡΡ ΠΠ°Π·Π°Π½ΡΠΊΠΎΠ³ΠΎ ΠΠΎΡΡΠ΄Π°ΡΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ Π£Π½ΠΈΠ²Π΅ΡΡΠΈΡΠ΅ΡΠ°,.
Π ΠΎΡΡΠΎΠ²ΡΠΊΠΎΠ³ΠΎ ΠΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠ³ΠΎ Π£Π½ΠΈΠ²Π΅ΡΡΠΈΡΠ΅ΡΠ°, Π‘Π°ΡΠ°ΡΠΎΠ²ΡΠΊΠΎΠ³ΠΎ ΠΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠ³ΠΎ ΠΠ½ΡΡΠΈΡΡΡΠ°ΠΠΠ «Π¦Π΅Π½ΡΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ» (Π³. Π’ΡΠΌΠ΅Π½Ρ).
2) Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ Π΄Π°Π½Π½ΡΡ ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΎ Π½ΠΎΠ²ΠΎΠ΅ ΠΏΡΠΈΠΊΠ»Π°Π΄Π½ΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ — «Π‘ΠΎΠ·Π΄Π°Π½ΠΈΠ΅ Π½Π°Π±ΠΎΡΠ° Π΄Π»Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΡΡΠ΄Π° ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ ΠΆΠ΅Π»ΡΠ΄ΠΎΡΠ½ΠΎ-ΠΊΠΈΡΠ΅ΡΠ½ΠΎΠ³ΠΎ ΡΡΠ°ΠΊΡΠ°».
ΠΡΠ±Π»ΠΈΠΊΠ°ΡΠΈΠΈ. ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ Π΄ΠΈΡΡΠ΅ΡΡΠ°ΡΠΈΠΈ ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Ρ Π² 3 ΡΡΠ°ΡΡΡΡ ΠΈ 5 ΡΠ΅Π·ΠΈΡΠ°Ρ Π΄ΠΎΠΊΠ»Π°Π΄ΠΎΠ².
Π²ΡΠ²ΠΎΠ΄Ρ.
1. ΠΡΠ΅Π΄Π²Π°ΡΠΈΡΠ΅Π»ΡΠ½Π°Ρ ΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΠ° Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² ΠΏΡΠΎΡΠ΅ΠΈΠ½Π°Π·ΠΎΠΉ Π ΠΏΠΎΠ²ΡΡΠ°Π΅Ρ ΡΠΎΡΠ½ΠΎΡΡΡ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ ΡΠΎΡΠΌ Π³Π΅Π½ΠΎΠ² K-ras, B-raf ΠΈ ΠΠ Π‘ Π² ΠΏΠ»Π°Π·ΠΌΠ΅ ΠΊΡΠΎΠ²ΠΈ.
2. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Ρ ΠΎΠΏΡΠΈΠΌΠ°Π»ΡΠ½ΡΠ΅ ΡΡΠ»ΠΎΠ²ΠΈΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΎΠ±ΠΎΠ³Π°ΡΠ΅Π½Π½ΠΎΠΉ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½ΠΎΠΉ ΡΠ΅ΠΏΠ½ΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΈΠΈ Ρ ΡΡΠ΅ΠΌΡ ΠΏΡΠ°ΠΉΠΌΠ΅ΡΠ°ΠΌΠΈ Π΄Π»Ρ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ K-ras ΠΏΡΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ ΠΠΠ ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ.
3. ΠΠ½Π°Π»ΠΈΠ· ΠΌΡΡΠ°ΡΠΈΠΉ Π³Π΅Π½Π° K-ras Π² ΠΠΠ ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΠΈΡΠΊΠ° ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Π½Π° ΠΏΡΠ΅Π΄ΠΏΡΠΈΡΡΠΈΡΡ Ρ Π²ΡΠ΅Π΄Π½ΡΠΌΠΈ ΡΡΠ»ΠΎΠ²ΠΈΡΠΌΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠ²Π°.
4. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Ρ ΠΎΠΏΡΠΈΠΌΠ°Π»ΡΠ½ΡΠ΅ ΡΡΠ»ΠΎΠ²ΠΈΡ Π°Π½Π°Π»ΠΈΠ·Π° Π³Π΅Π½Π° B-raf — Π΄ΡΡΠ³ΠΎΠ³ΠΎ ΠΊΠ»ΡΡΠ΅Π²ΠΎΠΉ Π³Π΅Π½Π° RAS-ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π°.
5. ΠΠ°ΠΈΠ±ΠΎΠ»ΡΡΠ°Ρ ΡΠ°ΡΡΠΎΡΠ° Π²ΡΡΡΠ΅ΡΠ°Π΅ΠΌΠΎΡΡΠΈ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ B-raf ΠΏΡΠΈΡ ΠΎΠ΄ΠΈΡΡΡ Π½Π° ΠΎΠΏΡΡ ΠΎΠ»ΠΈ ΡΠΈΡΠΎΠ²ΠΈΠ΄Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ, ΠΌΠ΅Π»Π°Π½ΠΎΠΌΡ ΠΈ ΠΎΠΏΡΡ ΠΎΠ»ΠΈ ΡΠΎΠ»ΡΡΠΎΠΉ ΠΊΠΈΡΠΊΠΈ. Π ΡΠ»ΡΡΠ°Π΅ ΠΎΠΏΡΡ ΠΎΠ»Π΅ΠΉ ΡΠΈΡΠΎΠ²ΠΈΠ΄Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΠΈ ΠΌΠ΅Π»Π°Π½ΠΎΠΌ Π½Π°Π»ΠΈΡΠΈΠ΅ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ Π-raf Π½Π΅ ΠΈΡΠΊΠ»ΡΡΠ°Π΅Ρ Π½Π°Π»ΠΈΡΠΈΠ΅ Π² ΡΠ΅Ρ ΠΆΠ΅ ΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΡΡ ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΠΌΡΡΠ°Π½ΡΠ½ΠΎΠΉ ΡΠΎΡΠΌΡ Π³Π΅Π½Π° K-ras.
6. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Ρ ΠΎΠΏΡΠΈΠΌΠ°Π»ΡΠ½ΡΠ΅ ΡΡΠ»ΠΎΠ²ΠΈΡ Π°Π½Π°Π»ΠΈΠ·Π° ΠΠ Π‘ — Π³Π΅Π½Π° Π΄ΡΡΠ³ΠΎΠ³ΠΎ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π° — WNT.
ΠΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΈ.
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