Ukuvela komdlavuza ekugcineni kungenxa yokungajwayelekile kwezakhi zofuzo, okwenza ukukhula kwamangqamuzana aguquguqukayo abe esimweni esingalawuleki, futhi amangqamuzana omdlavuza aqala ukuhlukana futhi ande ngenani ngokungapheli. Ngamanye amazwi, umdlavuza yisifo sofuzo. Kodwa-ke, izici zangaphandle ezifana nomfutho wempilo ephezulu, ukungatheleleki komzimba okuphansi, ukubhema nokuphuza, kanye nomsebenzi ongajwayelekile nokuphumula kuyimbangela yamaphutha ofuzo.
Izici ezihlobene nomdlavuza yilezi:
- age
- utshwala
- I-Carcinogen (aflatoxin)
- Ukuvuvukala okungapheli
- Imikhuba yokudla
- i-hormone
- Ukuzivikela komzimba
- Izifo ezithathelwanayo (i-hepatitis B, i-Helicobacter pylori)
- ukukhuluphala
- imisebe
- ukukhanya
- ugwayi
Ngemva kweminyaka engaphezu kweshumi yokuthuthuka, ukuhlolwa kofuzo lomdlavuza sekuyisidingo esisheshayo senani elikhulu leziguli ezinomdlavuza. Isiqondiso sombiko wokuhlola esinikezwa ukuhlolwa kofuzo lwesimila sihambisana kahle nomqondo wokuthuthukiswa komuthi onembayo, futhi singene kuzo zonke izici zokuxilonga nokwelashwa kweziguli ezinomdlavuza, ukuze iziguli zikwazi ukukhetha imithi eqondiwe yokwelashwa okunembile, zigweme ukuchezuka, futhi zigweme okungadingekile. side effects baba.
Isimo samanje sokwelapha okubhekiswe kumdlavuza wesibindi
Kuphela ngokuhlukanisa izici ezibalulekile zomdlavuza wesibindi kusukela ezingeni lamangqamuzana lapho ukuxilongwa kusenesikhathi kanye nokwahlulela kokubikezela kwesimila kube okunengqondo futhi kunembile, futhi izidakamizwa ezihlosiwe zamangqamuzana zingasetshenziswa ukwenza umuntu uqobo nokwelapha iziguli ngokunembile. Imithi ehloselwe umdlavuza wesibindi egunyaziwe imi kanje:
1. ISorafenib (iSorafenib, iDorjemi)
I-Sorafenib yisidakamizwa esiqondisiwe esinemiphumela emibili. Eyokuqala ukuvimbela imithambo yegazi emisha edingekayo ekukhuleni kwesimila, futhi ingakhomba namaprotheni akhuthaza ukukhula kwamangqamuzana omdlavuza. Okuqondiwe okuyinhloko yi-VEGFR-1 / 2/3, RET, FLT3, BRAF njalonjalo.
I-Sorafenib ingavimbela ngokuqondile ukwanda kwamangqamuzana e-tumor, futhi ingase futhi isebenze ku-VEGFR ne-PDGFR ukuze ivimbele ukwakheka kwemithambo yegazi emisha futhi inqamule ukunikezwa okunomsoco kwamangqamuzana e-tumor, ngaleyo ndlela inqande ukukhula kwesimila. I-Sorafenib ifanelekela ukwelashwa kokuqala komdlavuza wesibindi othuthukisiwe ongakwazi ukuhlinzwa noma ukumetastasized.
I-Sorafenib ngumuthi womlomo, kabili ngosuku. Imiphumela emibi kakhulu yalo muthi ifaka ukukhathala kwezintende zezandla noma amathe, ukuqubuka, ukungathandi ukudla, isifo sohudo, umfutho wegazi ophakeme, ububomvu, ubuhlungu, ukuvuvukala noma amabhamuza. Imiphumela emibi kakhulu (engajwayelekile) ifaka phakathi izinkinga zokugeleza kwegazi liye enhliziyweni nokugcwala kwesisu noma kwamathumbu.
2.regorafenib (Regofenib, Baivango)
I-Regefenib ingavimba i-tumor angiogenesis, futhi ingakhomba namaprotheni amaningana ebusweni bamangqamuzana omdlavuza ukuvimbela ukukhula kwamangqamuzana omdlavuza. Kuyi-oral multi-target kinase inhibitor engavimbela i-VEGFR-1, 2, 3, TIE-2, BRAF, KIT, RET, PDGFR ne-FGFR, futhi ukwakheka kwayo kuyefana ne-sorafenib.
NgoDisemba 12, 2017, i-State Food and Drug Administration (i-CFDA) yavuma i-oral polykinase inhibitor regorafenib yeziguli ezine-hepatocellular carcinoma (HCC) ezazithole ukwelashwa kwe-sorafenib phambilini. Thatha ngomlomo kanye ngosuku amasonto ama-3 alandelanayo, bese uphumula isonto, bese uqhubekela emjikelezweni olandelayo.
Imiphumela emibi ejwayelekile ifaka phakathi ukukhathala, ukungathandi ukudla, i-hand-foot syndrome (ukuba bomvu nokucasuka kwezandla nezinyawo), umfutho wegazi ophakeme, umkhuhlane, ukutheleleka, ukwehla kwesisindo, isifo sohudo nobuhlungu besisu. Imiphumela emibi kakhulu (engajwayelekile) ingafaka ukulimala okukhulu kwesibindi, ukopha okukhulu, izinkinga zokuhamba kwegazi lenhliziyo, nokugcwala kwesisu noma kwamathumbu.
3.lenvatinib (Levatinib, Le Weima)
ILenvatinib yisidakamizwa esiqondiswe kakhulu. Izinhlosongqangi ze-levatinib zifaka phakathi i-vascular endothelial growth factor receptor VEGFR1-3, i-fibroblast growth factor receptor FGFR1-4, i-platelet-etholwe ukukhula factor receptor PDGFR- α, cKit, Ret et al. Sebenza ngokuvimbela izicubu ekwakheni imithambo yegazi emisha edinga ukukhula.
Ngo-Agasti nonyaka, u-Eisai (Eisai) noMerck (MSD) we-lovastinib bavunywa yi-US FDA ukuthi bayikhangise. U-Leweima wafakwa ekwelashweni komugqa wokuqala komdlavuza wesibindi ongaphambi kokuhlinzwa ngomkhombandlela womdlavuza wesibindi we-CSCO (inguqulo ka-2018), okuyisiqondiso esinegunya kunawo wonke somhlahlandlela nokwelashwa eChina.
I-Lenvatinib ilawulwa ngomlomo kanye ngosuku. Imiphumela emibi kakhulu yalo muthi i-palmar-footed redness syndrome, ukuqubuka, ukungathandi ukudla, isifo sohudo, umfutho wegazi ophakeme, ubuhlungu bamalunga noma besisipha, ukwehla kwesisindo, ubuhlungu besisu noma amabhamuza. Imiphumela emibi kakhulu (engajwayelekile) ingafaka izinkinga zokopha nokulahleka kwamaprotheni emchameni.
4. ICabozantinib (Cabozantinib)
I-Cabozantinib (i-Cabozantinib) iyinhlayiyana encane ye-multi-target inhibitor eyenziwe yi-Exelixis yase-United States, engakhomba i-VEGFR, MET, NTRK, RET, AXL ne-KIT. XL184 ”.
NgoMeyi 29, 2018, i-FDA ivume iCarbotinib ukwelashwa komugqa wesibili komdlavuza wesibindi osezingeni eliphakeme. Ukuvunyelwa kususelwa esivivinyweni somtholampilo weSigaba III se-CELESTIAL. Iziguli ezine-hepatocellular carcinoma esezithuthukile ngemuva kokwelashwa nge-sorafenib zikuthuthukise kakhulu ukusinda okuphelele uma kuqhathaniswa ne-placebo. Ukusinda okungenazinqubekela phambili kanye nezinga lokuphendula ngenhloso nakho kuthuthuke kakhulu.
I-5.nivolumab (i-Navumab, i-Opdivo®)
I-Opdivo isiza amasosha omzimba ahlasele amangqamuzana omdlavuza ngokukhomba indlela yokusayina yeseli ye-PD-1 / PD-L1 (i-PD-1 ne-PD-L1 zingamaprotheni akhona kumaseli omzimba wokuzivikela kanye namaseli athile omdlavuza). Ngokwemibandela yabantu abavamile: Ngokuvimbela ukuboshwa kwephrotheni ye-PD-L1 kumaseli omdlavuza, ukufihlwa kwamangqamuzana omdlavuza kuyavinjelwa, futhi amangqamuzana okuzivikela omzimba angakwazi ukubona futhi aqede amangqamuzana omdlavuza.
NgoSepthemba 23, 2017, ngokwesilingo somtholampilo seCheckmate-040, i-US FDA yavuma i-Opdivo yeziguli ezinomdlavuza wesibindi osezingeni eliphezulu ngemuva kokwehluleka ukwelashwa kwe-sorafenib (dojime): isilinganiso esisebenzayo esingu-20%, isilinganiso sokulawula izifo esingu-64%.
6.i-larotrectinib (Larotinib, igama lokuhweba i-Vitrakvi)
I-Larotrectinib (igama elijwayeleke kakhulu kungenzeka ukuthi yi-LOXO-101) lavunywa yi-FDA ngoNovemba 27, 2018 ekwelapheni iziguli zabantu abadala nezengane ezinezicubu eziqinile ezithuthukile endaweni noma ezine-metastatic ezine-NTRK gene fusion. Lo muthi ohlosiwe awusebenzi nje kuphela, kepha futhi ungumuthi olwa nomdlavuza obanzi, osebenza kwizicubu eziningi ezihlukene! Uma nje uhlolwe ufuzo futhi kukhona i-NTRK1, NTRK2, noma i-NTRK3 gene fusion, ungakhetha lesi sidakamizwa sokulwa nomdlavuza esingahlukanisi izinhlobo zezicubu.
Ungakhetha kanjani ukuhlolwa kofuzo kweziguli ezinomdlavuza wesibindi?
Ochwepheshe be-Global Oncologist Network batshele ngokucacile abangani babo ukuthi ukuhlolwa kwezakhi zofuzo zomdlavuza kanye nokuhlaziywa kokwelashwa komtholampilo kuyiphrojekthi ehlelekile edinga ukusekelwa okuqinile kwelabhorethri, ukulawulwa kwekhwalithi ephezulu yokuhlola kanye nezinga eliphezulu leqembu lokuhlaziya idatha. Ukuhlaziywa okuhle kokuhlolwa kofuzo kungasindisa izimpilo zeziguli ezinomdlavuza, futhi umbiko wokuhlaziya i-patchwork uzokwenza iziguli zilahlekelwe ithuba lokwelashwa. Njengamanje, kunenqwaba yezikhungo zokuhlola izakhi zofuzo emakethe, futhi iziguli kufanele zikhethe ngokucophelela izinkampani zokuhlola izakhi zofuzo ukuze ziqinisekise ukunemba kwemiphumela yokuhlolwa.
Abahleli abalandelayo bazokwethula ubuchwepheshe obucacile bokuhlola izakhi zofuzo e-United States!
1. Keris multi-platform ukuhlaziywa kwamangqamuzana ubuchwepheshe
Ubuchwepheshe bokuhlaziywa kwamangqamuzana amaningi e-Careris Cancer Precision Therapy of Careris Life Sciences e-United States kuyindlela efanelekile yokuhlolwa kofuzo kweziguli ezinomdlavuza, ngoba akubandakanyi kuphela ukuhlolwa kwezakhi zofuzo ezingeni le-DNA kepha futhi ne-RNA ne-mo ehlobene namaprotheni
ukuhlolwa kwamakhemikhali. Zonke ezinye izinkampani ezihlola izakhi zofuzo azinazo. Ngenxa yamasu wokuhlaziya ahlukahlukene, ubuchwepheshe bokuhlaziywa kwamangqamuzana amaningi bungahlaziya ukuhluka kwesigaxa sesiguli ngokuqondakala nangokubanzi, futhi ukuqondiswa kwezidakamizwa okunikeziwe kunegunya kakhulu.
Ngokuya ngemininingwane esemthethweni yaseKeruis, isifundo esikhulu esiqinile sesimila seziguli eziyi-1180 ezibhalisiwe, ngemuva kokuholwa yi-Keruis multi-platform ukuhlaziywa kwamangqamuzana, iziguli zihlala isikhathi eside Izinsuku ezingama-422 . Inani elijwayelekile lemithi yeziguli ezingaphansi kokufundiswa ngu-3.2, futhi inani lemithi yeziguli ngaphandle kokuholwa ngu-4.2. Imithi eminingi isho ukuthi iziguli zingadinga ukuhlupheka imiphumela emibi kanye nokulahleka okungadingekile komnotho. Lokho iziguli ezingacabangi ukuthi, ngaphezu kokuqondisa ukukhethwa kwezidakamizwa ezihlosiwe, uKerrys angabuye ahlaziye ukuthi yimiphi imishanguzo ye-chemotherapeutic elungele iziguli. Eqinisweni, ukukhethwa kwemithi yokwelashwa ngamakhemikhali futhi kudinga ukuholwa, futhi akukwazi ukukopishwa ngokuya ngemikhombandlela yokwelashwa. Ukuhlaziywa kwe-Keris multi-platform yamangqamuzana ubuchwepheshe obuningi obuningi bokuhlaziya ukuhlinzeka iziguli ngezindlela zokwelashwa ezinembe kakhulu nezifanelekile.
Ama-careers ama-multi-platform ukuhlaziywa kwamangqamuzana aqondisa ukwelashwa ukumboza cishe zonke izinhlobo zomdlavuza
Izinhloso ezivame kakhulu zokuhlaziywa kwamangqamuzana e-Keruis njenge-EGFR, ALK , ROS1 , MET , mTOR , BRAF , HER2 njalonjalo, kanye nezinhloso ze-immunotherapy PD-L1 , TMB kanye ne-MSI-H , umbiko wokuhlola ungaqondisa iziguli ukuthi zikhethe. okuhlosiwe Ukwelashwa okunembile kwemithi kusiza iziguli zigweme ukuchezuka futhi zigweme imiphumela emibi engadingekile. Ngisho noma kungekho okuhlosiwe kokuguqulwa kwezakhi zofuzo futhi lingekho ithuba lokukhetha izidakamizwa ezihlosiwe, i-Keruis ingaphinde iqondise ukusetshenziswa kwezidakamizwa ze-chemotherapy nezidakamizwa ze-hormone ngokusekelwe emiphumeleni yokuhlaziya, futhi inikeze ithuba lokubamba iqhaza ezivivinyweni zakamuva zomtholampilo e-United States.
2. IsisekeloOne®CDx
I-FoundationOne®CDx yamukelwa yi-FDA njengomkhiqizo wokuqala wokuxilonga ohlobo lwe-pan-tumor. Njengethuluzi lokucwaninga, lisize ukutholakala kwemiphumela yocwaningo lwesayensi engenakubalwa, futhi laqoqa idatha enkulu ngalesi sikhathi. Ukutholakala kokuhlolwa kwamanje kufaka izakhi zofuzo ezingama-324 namamaki amabili wamangqamuzana (MSI / TMB) angabikezela ukusebenza kwama-inhibitors wokuhlola amasosha omzimba. Ingamboza zonke izicubu eziqinile (ngaphandle kwesarcoma) futhi ingahambisana ngqo nezindlela zokwelapha ezihlosiwe eziyi-17 ezivunyelwe yi-FDA!
Ekuhlolweni komtholampilo kwezakhi zofuzo zomdlavuza, amasu asetshenziswa ngokuvamile ahlanganisa ukulandelana kwe-Sanger, i-mass spectrometry genotyping, i-fluorescence in situ hybridization (FISH) kanye nokuhlaziywa kwe-immunohistochemical (IHC). “Ukutholwa komaka okukodwa okujwayelekile” okufana ne-FISH , IHC kanye nokutholwa kwe-hotspot yezakhi eziningi zofuzo ( hotspot panel ) kungathola kuphela uhlobo olulodwa noma ezimbili zokungajwayelekile okubalulekile kofuzo okubalulekile (njengokushintshwa okuyisisekelo kuphela). Ucwaningo luye lwabonisa ukuthi ubuchwepheshe bakamuva obuphelele bokulandelana kwesizukulwane esilandelayo bokuhlolwa kofuzo okuphelele komdlavuza bungahlonza zonke izinhlobo ezine zokungajwayelekile kwezakhi zofuzo (ukushintshanisa okuyisisekelo; ukufakwa nokususwa; ukuhluka kwenombolo yokukopisha nokuhlelwa kabusha), futhi inembe kakhulu kunokuhlola okuvamile, okujwayelekile.
