I-EML4-ALK ku-Cancer Lung kanye nendima ye-Crizotinib
Uma udokotela wakho ekutshele ukuthi une-ALK rearrangement noma umdlavuza wamaphaphu we-ALK, ungase uzizwe sengathi ukhona ezweni elikhuluma ulimi lwangaphandle ngaphandle komhumushi. Yini ngempela i-ALK, i-rearrangement ye-ALK evamile kangakanani, futhi abantu abanomdlavuza we-ALK-positive baphathwa kanjani?
Incazelo yokuguquguquka kwe-ALK
Ukulungiswa kabusha kwe-ALK kuyinto engavamile esakhiweni esingase senzeke emangqamuzaneni omdlavuza njengamaseli omdlavuza wamaphaphu.
Njengokubuyekezwa okusheshayo, izakhi zofuzo ziyingxenye yama-chromosomes ku-DNA yethu leyo ikhodi yezinto ezifana nombala weso nombala wezinwele. Ziyizinhlelo zokuthi amaprotheni asebenze izinqubo ezigcina imizimba yethu isebenza kahle-noma idale amangqamuzana ahlukanise futhi akhule.
Amangqamuzana omdlavuza amangqamuzana athola ukushintshashintsha kwezakhi zofuzo-izinguquko ezakhiweni zofuzo-ekusebenzeni kwamangqamuzana omdlavuza. Njengabantu, yonke imdlavuza ihlukile futhi ithwala izinguquko ezihlukahlukene kanye nezinguquko zofuzo. Lezi zakhi zofuzo ziguqule ikhodi ye-protein engavamile futhi yenza imisebenzi engavamile-njengokushayela ukukhula komdlavuza.
Kutholakale ngo-2007, ukuguquguquka kwe-ALK kuyishintsho esakhiweni okuthiwa i-ALK (i-anticlastic lymphoma kinase.) Ukuze kube nokuqondile, lokhu kuguquka kuyi-rearrangement yesakhi-ukuhlanganiswa kwezakhi zofuzo ezimbili ezibizwa ngokuthi i-ALK ne-EML4 (amaprotheni e-echinoderm microtubule ehlobene njengo-4.) Lesi sakhi esingavamile (i-gusion ye-fusion) ngamakhodi we-protein engavamile okuthiwa i-tyrosine kinase (kunezinhlobo eziningi ze-tyrosine kinases.)
I-Tyrosine kinases yi-enzymes (amaprotheni) enza njengezithunywa zamakhemikhali, ukuthumela amasignali esikhungweni sokukhula samaseli esitshela ukuthi iseli lihlukanise futhi lande. Ngokulula, i-tyrosine kinase "iyashayela" noma ibeka ukukhula komdlavuza (izinguquko ezifana ne-EML4-ALK fusion geni ziyaziwa ngokuthi "ukuguqulwa komshayeli.")
Ingxenye ejabulisayo yalokhu kutholakala ukuthi manje ezinye zegciwane zingelashwa nge-tyrosine kinase inhibitors, izidakamizwa ezivimbela u-tyrosine kinase (kuleli cala iphrotheni ye-fusion EML4-ALK) nokuvimbela ukukhula komdlavuza ngokuvimbela izimpawu ezitshela iseli ukuhlukanisa. Ngempela ukulawula ukushintsha komdlavuza we-"off-off", le mithi ithuthukise izimpilo zabanye abantu abaphila nomdlavuza abanezakhi zomzimba ze-ALK.
Abanye abantu bajwayele olunye ushintsho olutholakala kwabanye abantu abanomdlavuza wamangqamuzana ongewona omncane, obizwa ngokuthi i- EGFR mutation . Lokhu kuguqulwa kuholela ekubunjweni kwamaprotheni angavamile e-tyrosine kinase, kanti i-EGFR tyrosine kinase inhibitor uTarceva (erlotinib) uye wandisa impilo yabantu abaningi abanomdlavuza wamaphaphu abanomzimba omuhle okwenza lokhu kuguquka.
Izihloko ezilandelayo zikhuluma ngokubaluleka kokuguqulwa kwamangqamuzana omdlavuza:
Iyini i-ALK-Positive Cancer Lung?
I-ALK umdlavuza wamaphaphu omuhle ubhekisela kubantu abanomdlavuza wamaphaphu ovivinya okwenziwe ukuguquguquka kwe-ALK (i-gene EML4-ALK fusion.) Lokhu kuguquka kukhona ngamaphesenti amathathu kuya kwayisishiyagalolunye abantu abanomdlavuza wamangqamuzana ongewona omncane . Lokhu kungase kuzwakale njengenombolo encane ekuqaleni kokubona, kodwa ucabangela inani elikhulu labantu abathintekayo abanomdlavuza wamaphaphu minyaka yonke e-US (kulinganiselwa ukuthi bangaphezu kuka-200,000 ngo-2017), lelo nani ngempela likhulu kakhulu.
Ingabe i-ALK Rearrangements Kubonakala Kuphela Emdlalweni We-Lung?
Leli gciwane le-fusion ye-EML4-ALK litholakala nakwabanye abantu abanesifo se-neuroblastoma ne- amplastic cell cell lymphoma .
Ukucacisa ukuguqulwa komuntu kubantu abane-Cancer
Iphuzu elididekayo nelibalulekile okumele liphawule ukuthi i-EML4-ALK i-fusion ifulethi ayiyona inguquko yokuzalwa njenge-BRCA1 ne-BRCA2 yokuguquka komuntu kwabanye abantu abanomdlavuza webele (nezinye ezinye zegciwane.) Abantu abanomdlavuza wamaphaphu okwenziwe i-EML4 -I-Fusion i-fusion ye-fusion ayizalwanga ngamangqamuzana ayenalo ukuguqulwa futhi angayifumani i-tendency yokuba nalolu shintsho kusuka kubazali babo. Esikhundleni salokho, lokhu kuguqulwa okutholakele okuvela kwamanye amangqamuzana omdlavuza njengengxenye yokuthuthukiswa komdlavuza.
Ukuxilongwa
Ukuguqulwa kwe-ALK kutholakala ngokuprofetha kwamangqamuzana kwesampula se-tumor. Kubalulekile ekwenzeni lokhu kuhlolwa ukuthi kutholakala ukutholakala okwanele kwezicubu kusuka ekuhlinzekeni kwemitholampilo yamaphaphu noma ukuhlinzwa komdlavuza. Abacwaningi baphinde babheke izindlela zokunquma ukuthi ukuguqulwa kwe-ALK kukhona ngaphambi kokuhlolwa kofuzo, noma kungafaka indawo yokuhlolwa kofuzo. Izinto ezimbalwa eziphakamisa ukuguqulwa kwe-ALK kungenzeka kube khona zibandakanya:
- Umsebenzi wegazi - Isivivinyo okuthiwa i-CEA (carcinoembryonic antigen) sivame ukungabi namuntu kubantu abane-mutations alk.
- I-Radiology - Kwesinye isifundo, izicubu zithokozela i-ALK zibonakala ziqinile futhi zingenayo into ebizwa ngokuthi i-glass glass appearance. Ngokuphambene nalokho, amaphesenti angu-50 alabo abangenawo ukuguqulwa kwaba nokufundela i-radiology ngokubukeka kwesilazi.
Kodwa-ke, ngalesi sikhathi, ukuprofetha kwamangqamuzana (ukuhlolwa kofuzo) kuyisimo esihle kakhulu sokuhlolwa futhi kuyinqubo yokunakekelwa.
Ubani Okungenzeka Ukuba Nokushintshwa Kwe-ALK?
Izinhlobo zezinguquko ezikhona emangqamuzaneni yamaphaphu ziyahlukahluka kuye ngokuthi uhlobo lomdlavuza wamaphaphu . I-EML4-ALK i-fusion izakhi zofuzo zivame kakhulu kubantu abanehlobo lomuthi ongasona omncane wesifo samaphaphu okuthiwa i- lung adenocarcinoma . Lokho kuthiwa, ezimweni ezingavamile, i-ALK itholakele kubantu abane- squamous cell carcinoma yamaphaphu (olunye uhlobo lomdlavuza wesifo samangqamuzana ongewona omncane) nomdlavuza omncane wamangqamuzana wamaphaphu .
Kukhona nabantu abathile abangase babe ne-ALK ye-fusion geni. Lokhu kufaka iziguli ezincane, abantu abangazange bapheze (noma baphuze kakhulu), abesifazane, nalabo abane-Eastern Asia ubuhlanga . Esikhathini sokutadisha kwakamuva, kwatholakala ukuthi iziguli ezingaphansi kweminyaka engama-40 zivivinyelwe ukuthi i-EML4-ALK i-fusion ifulegi cishe amaphesenti angu-50 ngesikhathi (ngokuphambene namaphesenti amathathu kuya kwangu-5 abantu bonke ubudala abanomdlavuza wamaphaphu.)
Ngubani okufanele ahlolwe ukuguqulwa kwe-ALK (ukuhlelwa kabusha)?
Izinhlangano eziningana ziye zasebenza ndawonye ukuthuthukisa imihlahlandlela yokuthi ngubani okufanele ahlolwe ukuguqulwa kwe-ALK. Isivumelwano sokuthi zonke iziguli ezine-advanced adenocarcinoma kufanele zihlolwe kokubili ukuguqulwa kwe-ALK ne-EGFR, kungakhathaliseki ukuthi ubulili, umlando wokubhema, ezinye izinto eziyingozi, kanye nohlanga.
Omunye umkhawulo wukuthi ezinye izicubu zinemikhakha ebonakala sengathi iyinhlobo yomdlavuza wemaphaphu. Isibonelo, izicubu ezingxenyeni ezithile ze-biopsy zingahle zibukeke njenge-adenocarcinoma futhi izicubu kwezinye izingxenye zesampula ye-biopsy zingase zibukeke njengomdlavuza omncane weseli wamaphaphu.
Kukhona okunye okungafani odokotela abangayenza kule mihlahlandlela. Isibonelo, ukuhlolwa kunganconywa umuntu ongakaze afune ukubhema, yize uhlobo lwabo lomdlavuza wamaphaphu lungabonakali li-adenocarcinoma. Lezi ziqondiso zizoshintsha njengokunye okufundwayo mayelana nalezi zinguquko, kanti ezinye zinguquko zitholwa futhi zokwelashwa ezalandela.
I-ALK I-Cancer Positive Lung Yenziwa Kanjani?
Ngisho noma ukulungiswa kabusha kwe-ALK emdlavuza wamaphaphu kwavele kutholakala ngo-2007, ukwelashwa (manje okwesine) kubantu abanalo lomsindo (futhi banomdlavuza wamaphaphu) kuye kwavunywa yi-FDA. Ukuvunyelwa kwe-FDA - eminyakeni engaba ngu-4 kuphela ukutholakala kokuhlelwa kabusha - kuyathakazelisa phakathi kwesizinda semithi yomdlavuza wamaphaphu engakhulanga ngokuqhubekayo emashumini eminyaka edlule.
Ake siqale ngokukhuluma ngomuthi wokuqala ovunyelwe, bese usho imithi eyengeziwe manje evunyelwe kulabo abane-rearrangements ye-ALK
Isebenza kanjani ? Imithi - i- Xalkori (crizotinib) iyisimiso se-tyrosine kinase. Kulokhu, i-Xalkori ibophezela kumamukeli we-tyrosine kinase ebusweni bamangqamuzana omdlavuza wamaphaphu futhi ivimbela iphrotheni engavamile. Indlela elula yokuqonda lokhu ukucabanga nge-receptor ye-tyrosine kinase njengekhikhi, kanye neprotheni ye-tyrosine kinase (eyenziwe igesi elingavamile) njengesihluthulelo. Abantu abanokushintshashintsha kwe-ALK banesihluthulelo esingavamile. Uma ukhiye "ufakwe," izimpawu zithunyelwa esikhungweni sokukhula ukuze amaseli ahlukane ngaphandle kokuma. Imithi efana nokusebenza kwe-Xalkori ngokuvimbela isihluthulelo - uhlobo oluthandayo uma ugcwalisa isikhombi emnyango wakho wangaphambili ngekhonkrithi. Njengoba ukhiye (iphrotheni engavamile) engakwazi ukungena ngemvume (zibophe i-receptor,) isignali yeseli ukuhlukanisa nokukhula akalokothi ifinyelele esiteshini sokulawula nokuhlukaniswa kwamaseli (ukukhula kwesisu) kumisiwe.
Isebenza kahle kangakanani? Ucwaningo luye lwathola ukuthi ukwelashwa nge-Xalkori kuphumela ekusindeni okungahambisani nokuqhubeka kwezinyanga ezingu-7 kuya kwezingu-10. Kukhona isilinganiso esiphezulu sama-50 kuya ku-60% esiphenduli sempendulo kumuthi. Lokhu kungase kungabonakali okumangalisayo, ikakhulukazi uma kuqhathaniswa nokwelashwa kwamanye amanyevuza, kodwa kuyaphawuleka ukuthi abantu kulezi zifundo sebevele bathole futhi behlulekile ukwelashwa kwamakhemikhali wangaphambili futhi izinga lokuphendula elilindelekile lokuqhubeka nokwelashwa kwamakhemikhali lendabuko lizoba ngu-10% kuphela ukuqhubeka okuqhubekayo okuqhubekayo kwezinyanga ezintathu.
Ngisho noma izinga lokuphendula ne-Xalkori lingcono kunamakhemikhali ajwayelekile, izifundo azitholanga ukuthi i-Xalkori yandisa ukusinda jikelele . Kodwa ngenkathi kusinda kubalulekile, izinga lokuphila kubalulekile. Ukuyeka ukuqhubeka komdlavuza kunganciphisa izimpawu ezihlobene nomdlavuza, futhi empeleni, iziguli eziphathwe nge-Xalkori zinezimpawu ezimbalwa ezihlobene nomdlavuza wamaphaphu ( ukuphefumula okuncane, ubuhlungu besifuba nokukhathala.) Akuqinisekiseki ukuthi lolu cwaningo luhlolwe ngokunembile yini isilinganiso sokusinda kusukela abantu kulolu cwaningo bavunyelwe "ukuwela" futhi basebenzise olunye ukwelashwa uma izimpawu zabo ziqhubeka. Abantu abaningi bayeka imithi ye-chemotherapy futhi bashintshela ku-crizotinib kunezinye izindlela.
Njengoba i-Xalkori ivunyelwe, ezinye izidakamizwa ziye zavunyelwa ukwelashwa komdlavuza we-ALK-positive wamaphaphu. Lokhu kufaka:
- I-Zykadia (ceritinib)
- I-Alectinib (i-alencensa)
Ngaphezu kwalokho, isidakamizwa esisha sokubhekana nomdlavuza wamaphaphu we-ALK, i-Alunbrig (brigatnib) ivunyelwe ngo-Ephreli 28, 2017.
Ngesikhathi samanje kucatshangwa ukuthi alectinib inikeza ukuqhubeka okuqhubekayo kokusinda mahhala kune-crizotinib (izinyanga ezingu-25.7 vs 10,4 izinyanga) futhi kunemiphumela emibi embalwa. Lokho kusho, kubalulekile ukukhuluma ne-oncologist yakho ngokuthi iyiphi yalezi zidakamizwa kungenzeka ukuthi ikusebenzele kangcono.
Kubalulekile ukukhumbula ukuthi i-tyrosine kinase inhibitors ayilona ukwelashwa komdlavuza wamaphaphu , kodwa kunalokho into evumela ukuba isisu sibe "sigcinwe" njengoba nje imithi yesifo sikashukela ingalawula lesi sifo kodwa ayiyiphilisi. Kuthemba ukuthi esikhathini esizayo, umdlavuza wamaphaphu, okungenani izinhlobo ezithile ngezinguquko ezithile, zingaphathwa njengezinye izifo ezingapheli ezifana nesifo sikashukela.
Ukuphikiswa
Ngeshwa, nakuba abantu abangaphezu kwesigamu basabela kahle ekwelapheni, ukumelana njalo kuqhubeka isikhathi eside futhi umuthi ulahlekelwa ukusebenza. Kubantu abahlakulela ukuphikiswa, kusekhona izinketho ezitholakalayo. U-Alectinib wanikezwa ukuqokwa kwencwadi ngo-2013 kubantu abane-ALK-positive yomdlavuza wamaphaphu ukumelana ne-crizotinib. Ngo-Mashi ka-2014 omunye umuthi - iZykadia (ceritinib) - unikezwe ukwelashwa okuphumelelayo yi-FDA. Amazinga okuphendula okuqala eZykadia ayefana nalabo abane-Xalkori. Ngaphezu kwalokho - abantu abaningi abaye baphikisana no-Xalkori basabela kuZykada. Imithi emisha iqhutshwa ekuhlolweni kwemitholampilo kubantu abahlakulela ukuphikiswa, kanti abanye abacwaningi banethemba lokuthi esikhathini esizayo iziguli zingaphathwa ngendlela ehambisanayo nalezi zidakamizwa njengoba ukuphikisa kuqhubeka.
Ngaphezu kwalokho, izicubu zivame ukushintsha (ukuthuthukisa ushintsho olusha) ngokuhamba kwesikhathi. Ngezinye izikhathi imithi ehlose enye inguquko ephathekayo (efana ne-EGFR) ingasebenza noma ngabe isisu asizange sibe nesimo esihle sokuguquguquka kwe-EGFR. Kuthemba ukuthi esikhathini esizayo esiseduze sizokwazi ukwelapha umdlavuza wamaphaphu - okungenani le subtype - ngendlela efanayo ngendlela esiphatha ngayo ezinye izifo ezingapheliyo.
Iyiphi Imithi Engcono Kakhulu?
Izivivinyo zemitholampilo ziyaqhubeka zizama ukufunda okwengeziwe ngemithi emine manje etholakalayo isebenza kahle kakhulu. Kunobunye ubufakazi bokuthi izidakamizwa ezintsha (kokubili nge-ALK rearrangements kanye nezinye izinguquko) zingakwazi ukuphatha kangcono imetastase ebuchosheni. Ngenxa yobungozi begazi, uchungechunge lwe-capillaries oluboshwe ngokuqinile oluvimbela amathumba amaningi (okubandakanya i-chemotherapy kanye nemithi ehlosiwe) ukungena ebuchosheni, izidakamizwa eziningi esizitholakalayo manje zokwelapha umdlavuza wamaphaphu azikwazi ukusebenza ngokumelene nobuchopho izimiso zokugcoba. Kulabo abanezingcingo ezimbalwa zobuchopho, i-stereotactic brain radiotherapy (i-SBRT) noma i-cyber ummese inikeze ukhetho lokuphatha lezi, kodwa empeleni, esikhathini esizayo, sizoba nemithi engayibhekana nayo kangcono.
Ukuqapha Mayelana Nevithamini E Izithako
Sasiqaphelisa abantu njalo ngokuthatha noma yiziphi izithako ngenkathi benokwelashwa komdlavuza ngaphandle kokuqala ukukhuluma ne-oncologist yabo, futhi lokhu kubalulekile nge-crizotinib (futhi mhlawumbe nezinye izinqubo ezithintekayo). Ngo-2018 kwatholakala ukuthi ingxenye ye-vitamin E ebizwa ngokuthi i-tocopherol ingaphazamisa kakhulu ukwelashwa kwe-crizotinib. I-Vitamin E (noma okungenani le ngxenye) kokubili yanciphisa umsebenzi we-crizotinib, futhi ivinjelwe nomdlavuza wesifo sokufa ngenxa ye-crizotinib. Lokhu kubonakala kuwukuphela kwe-tocopherol, futhi hhayi enye ingxenye ye-vitamin E efana ne-y-tocopherol. Lokho kusho ukuthi izithako eziningi zevithamini E kanye nezinye izithako ezenziwe ngevithamini eziqukethe i-vitamin E zivame ukuba ne-tocopherol njengesithako esiholela phambili.
Imiphumela emibi yokwelapha
Njengazo zonke izindlela zokwelashwa zomdlavuza, imithi efana ne-Xalkori inemiphumela emibi. Ngokujabulisayo eziningi zalezi zinkulu kakhulu kunalokho abantu abakuthola ngesikhathi samakhemikhali endabuko. Izimpawu ezivame kakhulu abantu ababhekana nazo ku-Xalkori zihlanganisa izinkinga ezibukwayo, isifo sohudo, isicanucanu, ukuphefumula, nokuhlolwa okungavamile kwesibindi. Umphumela ongavamile kodwa obi kakhulu oye waqaphela ukuthuthukiswa kwezifo zamaphaphu ezingaphakathi okungaba yingozi.
Ikusasa
I-ALK ye-fusion i-gene iyingxenye yezinguquko eziningi ezisekhona kumangqamuzana omdlavuza wamaphaphu. Kuthemba ukuthi njengoba lezi ziqondwa kangcono, izifo ezintsha ezihlosiwe zizotholakala ezingeke ziphikisana nokuphikisana kuphela kodwa zihlose ezinye izinto ezingavamile (ukuguqulwa komshayeli) emangqamuzaneni omdlavuza. Ngokuphathelene ne-crizotinib, kucatshangwa ukuthi lesi sidakamizwa singasiza abanye abantu abangenalo i-ALK fusion yesakhi kodwa babe nezinye izakhi zofuzo ze-tyrosine kinase ezingavamile (njenge- rearrangement ye- ROS1 .)
Amazwana Wokugcina
Ukuze imishanguzo isetshenziswe ukuthi ihlose ukuguquguquka okunjenge-ALK, abantu abanomdlavuza wamaphaphu kumele bahlolwe ukuguqulwa komzimba. Ngenkathi izinkombandlela zincoma ukuthi wonke umuntu one-adenocarcinoma esezingeni eliphezulu futhi ukusetshenziswa kwalolu buchwepheshe landa, kunabantu abaningi abangakaze banikezwe uhlolo.
Kunezizathu ezimbalwa zalokhu. Esinye sukuthi lokhu kuyindawo eguquguqukayo kakhulu yomuthi, futhi akekho udokotela ongase abe ngaphezu kwazo zonke izibalo ezintsha. Buza imibuzo. Yenza ucwaningo oluthile (noma unomngane noma umthandayo ucwaninga isisu sakho.) Cabanga ukuthola umbono wesibili esikhungweni somdlavuza esibona umthamo omkhulu weziguli zomdlavuza wamaphaphu.
- Indlela Yokukhetha Isikhungo Sokwelashwa Kwe-Cancer
- Izinyathelo Zokuqala Uma Usanda Kuxilongwa Nge-Cancer Lung
- Indlela Yokuzivikela Ngomdlavuza
Okunye ukukhathazeka yizindleko. Imishanguzo emisha ehlose ukungajwayelekile emangqamuzaneni yomdlavuza ngokuvamile ifika ngomthamo wezindleko. Kodwa kunezinketho ezitholakalayo. Kulabo abangenawo umshuwalense, kukhona uhulumeni kanye nezinhlelo ezizimele ezingasiza. Kulabo abanomshwalense, izinhlelo zosizo lwe-copay zingasiza ukulahlekelwa izindleko. Kwezinye izimo, umenzi womuthi angakwazi ukuhlinzeka ngemithi ngezindleko ezincishisiwe. Futhi okubalulekile, njengomhlanganyeli ocaleni lomtholampilo , imithi, kanye nokuvakashelwa kwehhovisi, kuvame ukuhlinzekwa mahhala.
Njengombhalo wokugcina, kungakhathaliseki ukuthi ufunda kangakanani eqenjini lakho lezokwelapha, akukho okufana nokuzwa okuvela kubantu abaye base bekhona futhi bathola ukwelashwa okungenzeka uthole. Hlola amaqembu okusekela abantu abanomdlavuza wamaphaphu bese ubuza ukuthi ngabe ngubani omunye onguquko lwe-ALK. Ezinye izinhlangano ezifana ne-LUNGevity zinomsebenzi ofanayo (i-LUNGevity LifeLine) lapho zingakufanisa khona nomunye nomdlavuza wamaphaphu onomhlobo ofanayo nesigaba sesisu.
> Imithombo:
> Association American for Cancer Research. Izintsha ezitholakalayo Izivalo Ezivulekile Zama-Rational Lung Cancer Treatment Strategies. 09/18/14 .. http://blog.aacr.org/findings-open-doors-rational-lung-cancer-treatment-strategies/
> Bang, Y. Ukwelashwa kwe-ALK-Positive Non-Small Cell Lung Cancer. Archives of Pathology and Laboratory Medicine . 2012. 136 (10): 1201-4.
> Calio, A. et al. I-ALK / EML4 I-Gene Fusion Ingatholakala Ku-Carcinoma Engakahle Ye-Lung. I-Journal ye-Thoracic Oncology . 2014. 9 (5): 729-32.
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