Waxa la sameeyo oo ku saabsan iska caabbinta daroogada ee kansarka sambabada unugyada aan yarayn daawooyinka lala beegsaday, aad rabto in aad ogaato halkan
Lung cancer is the cancer with the highest morbidity and mortality in China. About 1.6 million people die of this disease each year worldwide, and about 85% of these cases are non-small cell lung cancer (NSCLC). At present, many cancer-targeting drugs have been developed for advanced kansarka sanbabada ee aan yareyn in the world. These new therapeutic drugs have increased the median survival time of patients to 35 months, which not only significantly prolonged their life span, but also achieved Personalized treatment. However, most patients will develop secondary drug resistance 8 to 14 months after receiving EGFR-TKI (standard first-line treatment for patients with sensitive mutations in the EGFR gene). How to solve the problem of drug resistance has become a hot research topic. Will continue to answer for everyone.
1. Maxay daaweyn loogu talagalay kansarka sanbabada ee unugyada yar?
Caabbinta daroogada bartilmaameedka ah ayaa badanaa loo qaybiyaa iska caabin asaasi ah iyo iska caabin labaad.
1. Daawada aasaasiga ah wuxuu loola jeedaa bukaanka isbadalkiisa bartilmaameedka EGFR, laakiin sababo la xiriira joogitaanka dabiiciga ah ee isbedelada hidda-wadaha KRAS, gefitinib iyo erlotinib hydrochloride kiniiniyada iyo daawooyinka kale ee la bartilmaameedsado waxtar ma leh, Ka dib 3 bilood ee la isticmaalo, iska caabinta daroogada ayaa dhacdo.
2. Iska caabinta daroogada sare: In the course of targeted drug treatment, because the target signal pathway continues to be inhibited by drugs, the buro produces other gene mutations in order to escape the drug, inhibiting the therapeutic effect of the targeted drug on the EGFR target, thereby Lead to drug resistance. The effective time of medication is usually more than 3 months.
2. Nidaamka iska caabinta daroogada ee daaweynta la bartilmaameedsaday ee kansarka sanbabada ee unugyada yar
There are currently three specific mechanisms for non-small cell kansarka sanbabada drug resistance. First, drug resistance is generated through genetic mutation. About 40% of the genes in patients with positive genetic tests will generate new genes from the original genes, which will cause insensitivity to the original drugs, resulting in drug resistance. Secondly, the cunning cancer cells will usually “repair the dark path of the plank road” and take a detour. This situation accounts for about 20% of patients with drug resistance. In addition to the above two drug resistance pathways, the drug resistance mechanism of the remaining 30% of patients is not yet clear.
3. Sidee loo xukumaa in bukaanada qaba kansarka sanbabada unugyada aan yareyn ay leeyihiin iska caabin daroogo?
1. Sida caadiga ah, marka daawadu ay adkaysato, dawada la beegsaday ma xakamayn karto koritaanka burada, taas oo keeni doonta in burodu ay korto ama barato meel fog. Waqtigaan, bukaanku wuxuu yeelan doonaa calaamado gaar ah, sida qufac la'aan ka hor, laakiin dhawaan bilaabay qufac, ama ka dib metastasis maskaxda Bukaanku wuxuu yeelan doonaa dawakhaad, madax-xanuun, matag sabab la'aan, bukaanada qaba metastasis lafaha waxay la kulmi doonaan xanuun, cadaadis dareemayaasha iyo calaamadaha kale. Waqtigaan, bukaanku wuxuu u baahan yahay inuu feejignaado.
2. Bukaannada laga yaabo inay yeeshaan iska caabbinta daroogada, sida ugu fiican ayaa ah inay aadaan cisbitaalka si ay dib ugu eegaan. Go'aanso in daroogada la bartilmaameedsaday ay u adkeysato calaamadaha burooyinka iyo baaritaanka sawirka.
4. Ka dib marka bukaanku yeesho iska caabinta daroogada, dhakhtarku wuxuu badanaa ku talinayaa biopsy labaad, maxay macnaheedu tahay
Guud ahaan marka laga hadlayo, dhammaan bukaanada qaba kansarka sanbabada ee qaata daawooyinka EGFR-TRI isla markaana leh horumarka cudurka waa inay maraan biopsy labaad.
1. Mar labaad nadiifi baarista cudurada si loo ogaado inay tahay kansar aasaasi ah oo cusub ama soo noqoshada kansarka.
2. Samee tijaabada labaad ee hidde-sidaha si aad u go'aamiso in ay tahay iska caabbinta daroogada ee uu sababay isbeddelka hidda-wadaha mar kale, oo la ogaado haddii uu jiro qorshe daaweyn cusub oo la beegsaday.
Ka-qaadista labaad waxay si dhakhso ah u ogaan kartaa horumarka cudurka, waxay muujin kartaa hababka iska caabbinta daawada, iyo samaynta qorshooyinka daawaynta ee ku habboon. Ka-qaadista labaad waxay badiyaa u qaybsantaa qayb ka-qaadista unugyada iyo ka-qaadista dareeraha ah. Ka-qaadista unugyada waxaa inta badan loo qaybiyaa thoracotomy biopsy, bronchoscopy biopsy iyo biopsy sambabada percutaneous. Bukaannada aan heli karin unugyada burooyinka, ka-qaadis dareere ah oo ku salaysan tignoolajiyada isku xigxiga hidda-wadaha dhiigga ee NGS ayaa loo dooran karaa si loo helo fursado daaweyn oo dheeraad ah.
5. Maxaan sameeyaa haddii iska caabinta daroogadu u muuqato ka dib jiilka koowaad ee TKI ee lagu bartilmaameedsado daaweynta kansarka sanbabada ee unugyada yaryar?
Jiilka koowaad ee EGFR-TKI waxaa kamid ah gefitinib, erlotinib, iyo icotinib.
Marka loo eego tilmaamaha NCCN, tijaabinta isbeddelka T790M ayaa markii ugu horreysay lagula taliyay ka dib jiilkii ugu horreeyay ee iska caabbinta EGFR-TKI. Xeelado kala duwan ayaa la qaatay iyadoo loo eegayo haddii bukaanku leeyahay astaamo, haddii uu jiro metastasis maskaxeed, ha ahaato horumar maxalli ah ama horumar badan.
1. Bukaannada qaba T790M wanaagsan: the talada ugu horeysa waa daaweynta Osimertinib, sii wad daaweynta TKI ee bukaanada leh horumarka gaabis ah, iyo daaweynta maxaliga ah ee bukaanka leh horumarka maxaliga ah, oo ay ku jiraan daaweynta shucaaca ee metastasis maskaxda, daaweynta shucaaca maxaliga ah ee hal nabarka ah Si aad u qaadato kemotherapy bukaanada leh horumar ballaaran.
2. Bukaannada T790M-taban: kiimoterabi ayaa laga yaabaa in la siiyo, ama immunotherapy may be selected based on the PD-L1 expression of the patient.
3. Bukaannada aan astaamaha u muuqan ka dib iska caabbinta daroogada: daaweynta deegaanka waa la qaadan karaa ama waa la sii wadi karaa jiilka daaweynta TKI. Bukaannada qaba kaliya metastases maskaxda, daaweynta maxalliga ah waa la tixgelin karaa, waxayna sii wadaa isticmaalka jiilka koowaad ee EGFR-TKI.
6. Mudo intee leeg ka dib qaadashada osimertinib ayaa horumarin doonta iska caabinta daroogada?
Osimertinib waa jiilka seddexaad ee EGFR-TKI daroogada lala beegsaday iyadoo celcelis ahaan celceliska muddada u adkeysiga daroogada ee qiyaastii 11 bilood. Si kastaba ha noqotee, codsiyada kiliinikada, bukaanno badan ayaa sidoo kale ku dhaca isbeddello iska caabin ah laba ama saddex sano ka dib markay qaataan osimertinib, sidaas Xaaladda gaarka ah ee waqtiga iska caabbinta oxitinib way ku kala duwan tahay qof ilaa qof.
7. Waa maxay habka iska caabinta daroogada ee osimertinib?
Nidaamka iska caabinta daroogada ee osimertinib waa mid aad u dhib badan, oo ay ku jiraan isbeddelka C797S, isugeynta MET / dib u habeynta RET / dib u habeynta ROS-1, kordhinta HER-2, isbeddelka BRAF, isbeddelka RAS, isbeddelka FGFR1, u beddelashada kansarka unugyada yaryar, Ma jiro hidde-side isbeddellada, iwm, iyo nidaamyada daroogada ee soo socda ee farsamooyinka iska caabinta kala duwan way ka duwan yihiin.
1. Isbedelada hidda-wadaha EGFR markale: Isbedelada EGFR796 iyo 797 waxay ahaayeen 24.7%, EGFR 792 mutations waxay noqdeen 10.8%, EGFR 718 iyo 719 mutations waxay noqdeen 9.7% -EGFR hidda, isbadal dib u adkaysi leh, waxayna gaarayaan 45% bukaanada oo dhan, waxayna kudhowyihiin kalabar dalka.
2. Isbedelada hiddo-wadaha kale: oo ay ku jiraan PIK3CA, BRAF, MET, RET, KRAS, iwm. Noocyo kala duwan oo hiddo-wadayaal ah oo aan caadi ahayn hiddo-wadaha kansarka sambabka ayaa ku lug leh oo aad u kala firdhay.
3. Isu beddelay kansarka sambabka unugyada yar.
8. Maxaa la sameeyaa ka dib daaweyn la beegsaday oo Oxitinib ah oo loogu talagalay iska caabinta daroogada?
Jiinisyada iska caabinta kala duwan, xalka bilowga ah waa sida soo socota:
1. Xaaladda seddex-geesoodka isbeddelka (C797S / T790M / 19-del), saameynta xulashada bugatinib ayaa ka wanaagsan osimertinib / gefitinib, saameyntana ma saameyneyso goobta ay ku kala sugan yihiin C797S iyo T790M. (1) Bugatinib oo ay weheliso fasalka anti-EGFR (cetuximab / panitumumab) waxay xoojin kartaa saameynta daaweynta ee isku-beddelka seddex-geesoodka ah, iyo isku-darka labada daroogo ayaa ciyaari kara saameyn isku-dhafan; (2) Bugatinib oo lagu daray Selumetinib (Simetinib) ayaa laga yaabaa inuu awood u yeesho inuu ka adkaado iska caabinta osimertinib ee uu keenay isbadalka C797S.
2. Beddelka EGFR C797S, tixgeli daroogada jiilka koowaad ee la bartilmaameedsaday oo lagu daro jiilka saddexaad ee la bartilmaameedsado, sida osimertinib oo lagu daro gefitinib / erlotinib. Wixii is-waafajinta, waad awoodi kartaa
dooro Bugatinib + VEGF daroogada la beegsaday.
3. Haddii ay jirto kaliya isbeddel C79CS, waxaad isticmaali kartaa jiilka koowaad ee EGFR inhibitor, sida gefitinib, erlotinib, icotinib.
4. Kordhinta MET waxay soo jeedinaysaa in osimertinib oo lagu daro MET inhibitors (camatinib, crizotinib, Savolitinib, iwm). Isbedelada BRAF waxay soo jeedinayaan in osimertinib lagu daro BRAF inhibitors (dalafinib + trametinib). Isbeddelka 'RET' wuxuu soo jeediyay in Osimertinib lagu daro Kabotinib, dabcan waa ka wanaagsan yahay Osimertinib oo lagu daro BLU-667.
Waxaa lagugula talinayaa in ka dib iska caabbinta oxetinib, ay ugu fiican tahay in markale la sameeyo baaritaanka hidda-socodka, oo la xusho daroogada ku habboon ee la beegsanayo iyadoo la raacayo bartilmaameedka isbeddelka si loo caawiyo daaweynta. Waxaa ugufiican in lala tashado dhakhtar xirfad leh daaweynta isku dhafan ee daawooyinka la bartilmaameedsado.
9. Dhibaatooyinka ay keento kansarka sanbabada ee unugyada aan yareyn ee lagu bartilmaameedsado
Bartilmaameedka daroogooyinka lagu bartilmaameedsaday baa cad, laakiin macnaheedu maahan inaysan jirin falcelinno qallafsan oo caafimaad oo aan dhici doonin. Dareen-celinta xun ee dawooyinka la bartilmaameedsado sida shubanka, borotiinka, dhiig karka, finanka u eg finanka iyo cudurka wadnaha ayaa si fiican loo yaqaan. In kasta oo daroogada la bartilmaameedsado ay ka hooseeyaan dawooyinka dhaqameed ee cytotoxic, haddana weli lama dhayalsan karo. Qaar ka mid ah fal-celinta aan caadiga ahayn ee dhibta badanaa way adag tahay in la ogaado sababta oo ah baaritaanka bukaan-eegtada, inta badan waxay keentaa cawaaqib xumo.
Tusaale ahaan, daaweynta erlotinib waxay sababi kartaa sare u qaadista beerka asymptomatic transaminase, iyo dhiigbaxa caloosha ayaa si dhif ah loo soo sheegaa, halka gefitinib uu yahay maaddada yar ee anti-EGFR ee lagu bartilmaameedsado, in kasta oo dheef-shiid kiimikaadkiisu badanaa yahay beerka Qiyaastii 4% ayaa kelyaha lagu sifeeyaa qaab nooc iyo dheef-shiid kiimikaad dheef-shiid kiimikaad ah, iyo kiliinik ahaan u nugul kelyaha oo xumaada, kaas oo hagaaga ka dib ka bixitaanka daroogada. Daaweynta daroogada la beegsanayo, falcelisyada daran iyo xitaa kuwa halista ah waa in laga fogaadaa sida ugu macquulsan. Dareen-celinta xun waxay saameyn ku yeelan doontaa kalsoonida bukaanka ee daaweynta. Falcelinno daran oo daran ayaa carqaladeyn kara habka daaweynta.
