Immunotherapy waxay isticmaashaa dawooyin si ay u caawiso habka difaaca jidhku si fiican u garto oo u burburiyo unugyada kansarka. Immunotherapy waxaa loo isticmaali karaa in lagu daweeyo bukaanada qaba kansarka mindhicirka sare.
Kahortaga isbaarada isdifaaca
Qeyb muhiim ah oo ka mid ah habka difaaca jirka ayaa ah awooda ay isaga difaacdo weerarada unugyada jirka ee caadiga ah. Tan awgeed, waxay u isticmaashaa borotiinada "isbaarada" unugyada difaaca jirka, kuwaas oo u dhaqma sida shideyaasha u baahan in ladaro (ama la damiyo) si loo bilaabo jawaab celinta difaaca jirka.
Unugyada kansarku mararka qaarkood waxay u isticmaalaan isbaarooyinkaan si ay uga joojiyaan nidaamka difaaca jirka inuu ku soo weeraro. Si kastaba ha noqotee, daawooyinka loogu talagalay isbaarooyinkaan waxay leeyihiin rajo weyn sida hababka daaweynta kansarka.
Drugs called checkpoint inhibitors can be used in people whose kansarka mindhicirka cells have tested positive for specific genetic changes, such as high levels of microsatellite instability (MSI-H), or one of the types of mismatch repair (MMR) Genetic changes.
Daawooyinkan waxaa loo isticmaalaa dadka kansarku wali sii korayo daweynta kemotherabi ka dib. Waxa kale oo loo isticmaali karaa in lagu daweeyo dadka aan kansarka laga saari karin qaliinka, soo noqoshada daawaynta ka dib (dib u soo noqoshada) ama ku faafay qaybaha kale ee jidhka (metastasis).
Approved immunotherapy daroogada
PD-1 inhibitor waa la ogolaaday
Pembrolizumab (Pembrolizumab, Keytruda) iyo nivolumab (Nivolumab, Opdivo) waa daawooyin bartilmaameedsada PD-1, borotiin ku jira unugyada habka difaaca jirka ee loo yaqaanno T unugyada kuwaas oo inta badan caawiya Ka hortagga unugyadan inay weeraraan unugyada kale ee jirka. Marka la xannibo PD-1, daawooyinkani waxay kor u qaadi karaan jawaabta difaaca unugyada kansarka.
On May 24, 2017, the US FDA approved the PD-1 inhibitor pembrolizumab (Pembrolizumab, Keytruda) for the treatment of solid buro patients with microsatellite highly unstable (MSI-H) / mismatch repair defects (dMMR), The tumor types cover 15 different malignant tumors, including colorectal cancer, small cell lung cancer, and cervical cancer.
Bishii Ogosto 2, 2017, Maamulka Cuntada iyo Dawooyinka ee Mareykanka (FDA) ayaa oggolaaday nivolumab (Navumab, Opdivo) daaweynta fluorouracil, oxaliplatin, iyo irinotecan. Microsatelite oo leh xasilooni darro aad u daran (MSI -H) Daaweynta kansarka mindhicirka mindhicirka ee dadka waaweyn ama carruurta (≥12 sano jir) ama cilado dayactir la'aanta (dMMR).
CTLA-4 inhibitor ayaa la ogolaaday
Ipilimumab (Yervoy) waa daawo kale oo xoojin karta jawaab celinta jirka. Kali looma isticmaali karo Waxay u baahan tahay in lagu daro nivolumab, oo xannibaadda CTLA-4, oo ah borotiin kale oo ku jira unugyada T.
Kiiskii guuleystay ee MSI-High (MSI-High) mCRC waa isticmaalka wadajirka ah ee nivolumab iyo ipilimumab, oo lagu qiimeeyay daraasadda Wajiga II CheckMate142. Daaweynta isku dhafan ayaa muujisay ORR (heerka jawaabta ujeedka) ee 49%, iyo 5 ka mid ah 119 bukaan ah ayaa lahaa CR (jawaab buuxda) iyo 53 PR (jawaab celin qayb ah). Bukaannada badankood (n = 82) waxay horey u heleen fluorouracil, oxaliplatin iyo irinotecan. Bukaanadan, ORR waxay ahaayeen 46%, 3 CRs iyo 35 PRs.
Marka loo eego xogta CheckMate-142, FDA waxay oggolaatay isku-darka (Nivolumab + Ipilimumab) ee loogu talagalay daaweynta bukaanka qaangaarka ah iyo carruurta 12 sano jir ah iyo wixii ka weyn, oo ay ku jiraan bukaanada mCRC ee qaba MSI-H ama cilladaha hagaajinta khaldan (dMMR), Bukaanadan ayaa horumar sameeyay ka dib daaweynta fluorouracil, oxaliplatin iyo irinotecan.
Fasiraadda codsiga MSI / dMMR ee daaweynta midabka kala-goynta
MSI waxaa loola jeedaa luminta hiddo-wadaha dayactirka ee khaldan ee ay keento methylation-ka DNA ama hidde-ku-baddelka hiddo-wadaha, taasoo keentay isbeddellada dhererka mikrosatellite-ka isku xigxiga ee soo noqnoqda. Daraasadu waxay ogaatay in MSI-H ay muhiim u tahay biomarker-ka burooyinka ku habboon difaaca jirka.
MSI waa xasillooni-darrada microsatellite, MMR (dayactirka aan habboonayn) waxaa loola jeedaa shaqada dayactirka hiddo-wadaha. Hidda-wadaha dayactirka bini-aadamka (hiddo-wadaha MMR) wuxuu sheegi karaa borotiinka dayactirka ee isku habboonaanta ka dib qorista iyo tarjumaadda. Haddii luminta muujinta borotiin kasta oo MMR ah ay sababi karto cilado ku yimaada shaqada dayactirka unugga, ismaandhaafka aasaasiga ah ee habka dhalmada DNA Khasaaraha shaqada dayactirka wuxuu keenaa isku soo ururin, taas oo horseedda dhacdada xasillooni darrada microsatellite (MSI). Qiyaastii 15% kansarka mindhicirka malawadka waxaa keena marinka MSI.
PCR waxaa loo isticmaali karaa in lagu ogaado dhererka goobaha microsatellite (microsatellites waa tandem soo noqnoqda ee taxanaha DNA-ga gaaban ee genome of eukaryotes) ee unugyada burooyinka DNA, ka dibna marka la barbar dhigo DNA-da unugyada caadiga ah. Caannimada iyo codsiga NGS (Sequencing Generation Second), marka lagu daro immunohistochemistry dhaqameed iyo ogaanshaha PCR, heerka microsatellite sidoo kale waxaa laga heli karaa goobta NGS. Si aad u fahamto hay'adaha baaritaanka hidda-socodka ee NGS ee gudaha iyo dibadda, fadlan la tasho 400-626-9916.
Intaa waxaa dheer, tijaabooyinka burooyinka (oo ay ku jiraan tijaabooyinka qalliinka iyo tijaabooyinka daloolka) ayaa sidoo kale loo isticmaali karaa baaritaanka immunohistochemical ee afar hiddo-wadaha aan khaldaneyn, oo ay ku jiraan: MLH1, MSH2, MSH6, iyo PMS2. Ilaa iyo inta mid ka mid ah afartaan borotiin la la'yahay, burooyinka waxaa iska leh dMMR, oo ah cillad ku timid shaqada hagaajinta khaldan. Haddii dhammaan afarta borotiin si togan loo muujiyo oo burooyinku yihiin PMMR, hawsha hagaajinta khaldan ayaa la dhammaystiray.
Baaritaanka hidda-socodka ee falanqaynta warbixinta MSI
Sawirka soo socdaa wuxuu muujinayaa bukaan ka socda Shabakada Global Oncologist Network oo laga helay inuu leeyahay MSI-H kadib baaritaankii MSI ee ay sameeyeen shirkada baaritaanka hidaha ee gudaha (400-626-9916). Bukaan-socodkaani waa mid nasiib badan oo ku habboon daaweynta jirka.
Bukaan kale oo ka tirsan Shabakadda Global Oncologist Network waxaa si wanaagsan u tijaabiyey US Keruis Gene (400-626-9916), dhammaan afartana borotiinna waxay ahaayeen kuwo wanaagsan (togan), taas oo macnaheedu yahay in bukaanku uu ahaa PMMR, isla markaana uusan ku habboonayn habka kor ku xusan ee Immunotherapy. .
Fasiraadda natiijooyinka imtixaanka ugu dambeeya waxaa loo qaybin karaa MSS (xasiloonida microsatellite), MSI-L (microsatellite low አለመ xasilloonida) iyo MSI-H (microsatellite high instability). Guud ahaan, dMMR waxay u dhigantaa MSI-H, pMMR waxay u dhigantaa MSS iyo MSI-L.
Taxaddarrada isticmaalka dawada PD-1
- Daawooyinkan waxaa la siiyaa faleebooyin faleebo (IV) gala 2dii ama 3dii toddobaadba mar.
- Dhibaatooyinka ay keento daawooyinkan waxaa ka mid ah daal, qufac, lallabbo, cuncun, finan, cunno xumo, calool istaag, kalagoys xanuun iyo shuban.
- Dhibaatooyinka kale ee aadka u daran waxay u dhacaan si aan badnayn. Mararka qaarkood, nidaamka difaaca ayaa weerari kara qaybo kale, oo laga yaabo inuu sababo dhibaatooyin halis ah ama halis gelinaya nolosha sanbabada, xiidmaha, beerka, qanjidhada soo saara hormoonka, kilyaha, ama xubnaha kale.
- Inta lagu jiro faleebada, xaalada jireed ee bukaanka ayaa u baahan in lala socdo waqtiga dhabta ah.
Taxaddarrada dawada Ipilimumab
- Daawadan waxaa loo isticmaalaa nivolumab (Opdivo) si loogu daaweeyo kansarka mindhicirka, laakiin keligaa lama isticmaali karo. Waxaa lagu maamulaa faleebada xididka (IV), badanaa 3dii asbuucba mar 4 wareeg oo daaweyn ah.
- Waxyeellooyinka ugu badan ee daawadan waxaa ka mid ah daal, shuban, finan iyo cuncun.
- Markaad isticmaaleyso daroogadaan, waxyeelooyinka halista ah waxay umuuqdaan kuwa aad ugafiican isticmaalka daawada PD-1. Sida daawada PD-1, daroogadani waxay sababi kartaa nidaamka difaaca jirka inuu weeraro xubnaha kale ee jirka, taas oo sababi karta dhibaatooyin daran oo ku dhaca mindhicirka, beerka, qanjidhada soosaara hormoonka, neerfaha, maqaarka, indhaha, ama xubnaha kale. Dadka qaarkiis, dhibaatooyinkaan soo raaca waxay noqon karaan kuwo nafta halis geliya.
- Inta lagu jiro faleebada, xaalada jireed ee bukaanka ayaa u baahan in lala socdo waqtiga dhabta ah.
Sidee loo doortaa daawooyinka difaaca jirka ee kansarka malawadka?
Khabiirka Maraykanka ee kansarka mindhicirka Dr. Chiorean ayaa yidhi, “Pembrolizumab ama nivolumab ayaa aad looga doorbidayaa bukaanka qaba MSI-H. Nivolumab oo lagu daray ipilimumab (CTLA-4 inhibitor) si dhif ah ayaa loo isticmaalaa. Waxaan u maleynayaa farqiga i
s very small. Similarly, some people may argue that CTLA-4 may be better tolerated by the inhibitory response, but I also feel that the toxicity is significantly higher. ”
Dr. Messersmith said that when he needed to quickly obtain therapeutic effects, he used nivolumab and ipilimumab combination therapy. Adding ipilimumab can get an additional 15%–20% response rate. If the patient is symptomatic, it can be added. Even though this may increase adverse reactions, the treatment effect is even greater. This requires an assessment of the patient’s physical condition.
If patients and their families have difficulty in choosing an immunotherapy drug, they can seek domestic authoritative colorectal cancer experts for consultation through the Global Oncologist Network (+91 96 1588 1588) to determine the final, more suitable treatment plan.
