I-EML4-ALK kwi-Cancer yengoma kunye neNdima yeCrizotinib
Ukuba ugqirha wakho akuxelele ukuba unokwenziwa kwe-ALK okanye umdlavuza we-ALK-positive, unokuvakalelwa ngathi ungozwe elithetha ulwimi lwangaphandle ngaphandle kwetolika. Yiyiphi i-ALK, ingaqhelekanga njani ukulungiswa kwe-ALK, kwaye abantu abanomdlavuza we-ALK-positive baphathwa njani?
Inkcazo ye-ALK Mutation
Ukulungiswa kwakhona kwe-ALK kuyinto engavumelekanga kwisigidi esingaba khona kumhlaza weseli ezifana neeseli zomhlaza wamaphaphu.
Njengokuhlaziywa okukhawulezayo, iigleji ziyingxenye zama-chromosomes kwi-DNA yethu ekhokelela izinto ezifana nombala wamehlo kunye nombala weenwele. Ziyimpawu kunye neeprogram ezisebenzayo iinkqubo ezigcina imizimba yethu isebenza kakuhle-okanye yenza ukuba iiseli zihlukane kwaye zikhule.
Iiseli zengqamana ziiseli eziye zatshintshwa iziganeko ezininzi zoguquko-zitshintsho kwiijethi-kwinkqubo yokuba nomhlaza weseli. Njengabantu, yonke umdlavuza uhlukile kwaye uguqula utshintsho oluthile kunye nokuguquka kwemfuza. Ezi zigulo zengqungquthela kwi-code yokuvula yeeprotheni ezingavamile kwaye zenza imisebenzi engavumelekanga-njengokuqhuba ukukhula komhlaza.
Kufunyenwe ngo-2007, ukuguqulwa kwe-ALK kukuguqulwa kwimizimba ebizwa ngokuthi i-ALK (i-plastiki lymphoma kinase.) Ukuze ichaneke ngakumbi, ukuguqulwa komzimba ngokwenene kuhlaziywa kwe-gene-ukuxuba kwamagciwane amabili ebizwa ngokuba yi-ALK kunye ne-EML4 (iproteinyini echinoderm microtubule njenge-4.) Lo gesi ongaqhelekanga (i-gene fusion) kwiikhowudi zokufumana iprotheni engavumelekanga ebizwa ngokuba yi-tyrosine kinase (zininzi iintlobo ze-tyrosine kinases.)
I-Tyrosine kinase zi-enzymes (iiprotheni) ezisebenza njengezithunywa zeemichiza, zithumela iimpawu kwiziko leqondo lokukhula elixelela ukuba iseli ukwahlula nokuphindaphinda. Ngokulula, i-tyrosine kinase "iqhuba" okanye icwangcisa ukukhula komhlaza (ukutshintshwa kwezinto ezifana ne-EML4-ALK fusion gene iyaziwa ngokuthi "utshintsho lomqhubi.")
Inxalenye ebangelisayo yolu thotholo kukuba ngoku i-cancer iyakuthatyathwa nge-tyrosine kinase inhibitors, iziyobisi ezithintela i-tyrosine kinase (kulo mzekelo iprotheni ye-fusion EML4-ALK) kwaye inqande ukukhula komhlaza ngokuthintela iimpawu ezixelela iseli ukwahlula. Ngokwenene ukulawula umtshintshi "wokutshintshwa" komhlaza, la mayeza aphucule ubomi bezinye abantu abaphila nomhlaza abanengxaki yokuguqulwa kwe-ALK.
Abanye abantu baqhelaniswe nolunye utshintsho olutholakala kwabanye abantu abanomdlavuza ongasetyenzana wesifo samangcwaba, obizwa ngokuba nguguqulelo lwe - EGFR . Olu tshintsho lubuye lubangele ukwakhiwa kweeprotheni ezingaqhelekanga ze-tyrosine kinase, kwaye i-EGFR tyrosine kinase inhibitor iTarvava (erlotinib) iye yandise ubomi babantu abaninzi abanomdlavuza wamaphaphu abanesifo esinesifo esinomdla ngenxa yolu tshintsho.
Amanqaku alandelayo athetha ngokubhekiselele kwendima yokutshintshaniswa kwintsholongwane yomhlaza:
Yintoni i-ALK-Positive Cancer Lung?
Umdlavuza wamaphaphu omuhle ubhekisela kubantu abanomdlavuza wemiphunga ukuba iimvavanyo ezintle zokuguqula i-ALK (i-EML4-ALK fusion gene). Olu tshintsho lubakho kwipesenti ezintathu ukuya kubahlanu zabantu abanomdlavuza ongaphantsi weli cell . Oku kungathi ngathi inani elincinci ekuqalekeni, kodwa sicinga inani elikhulu labantu abanomdlavuza ngomphunga unyaka ngamnye e-US (kulinganiselwa ukuba bangaphezu kwama-200 000 ngo-2017), elo nani linkulu kakhulu.
Ngaba i-ALK i-Rearrangements Iyabonwa kuphela kwi-Cancer Lung?
Le gene ye-fusion ye-EML4-ALK ifunyenwe nakwabanye abantu abane-neuroblastoma kunye ne- plastiki enkulu yeli cell lymphoma .
Ukucacisa ukuguquka komntu kubantu abaneCarcer
Iphuzu elididekayo kunye nelibalulekileyo ukuba uqaphele ukuba i-EML4-ALK fusion yegeni ayinalo ukuguquka komzuzwana njenge-BRCA1 kunye ne-BRCA2 intshukumo kwabanye abantu abanomhlaza wesibeleko (kunye nezinye i-cancer). Abantu abanomdlavuza wamaphaphu okwenziwe nge-EML4 -I-gene fusion ayizalwanga ngeeseli eziguqulekileyo kwaye azizange zizuze ukutyekela ukuguqulwa kwabazali babo. Kunoko, oku kuguqulwa okufumeneyo okuvela kwezinye iiseli zomhlaza njengengxenye yophuhliso lomhlaza.
Ukuxilongwa
Ukuguqulwa kwe-ALK kufunyaniswa ngeprofayili yeeleksile yesampuli yesisu. Kubalulekile ekwenzeni oku kuhlola ukuba ukubonelelwa ngokwaneleyo kwezicubu ezivela kumbhobho wepopopi okanye umhlaza wesifo somdlavuza. Abaphandi bajonga iindlela zokujonga ukuba ukuguquguquka kwe-ALK kukhoyo phambi kokuvavanywa kwemfuyo, okanye kunokuthatha indawo yokuvavanya i-genetic. Izinto ezimbalwa ezibonisa ukuba utshintsho lwe-ALK lunokuba lubandakanya:
- Umsebenzi wegazi - Uvavanyo olubizwa ngokuthi i-CEA (carcinoembryonic antigen) ludla ukuba lubi kubantu abaneenguquko ze-ALK.
- I-Radiology - Kwisifundo esinye, i-tumor ebonakalayo i-ALK ibonakala iyomeleleyo kwaye yayingenanto into ebizwa ngokuba yi-glass glass. Ngokwahlukileyo, iipesenti ezingama-50 zazingenalo utshintsho zazifundela i-radiology kunye nokubonakala kweglasi.
Ngeli xesha, nangona kunjalo, ukuprofetwa kwee molecular (ukuhlolwa kofuzo) kusekho uvavanyo oluhle kakhulu kwaye ngumgangatho wokunyamekela.
Ngubani omele ukuba ne-ALK Mutation?
Iindidi zenguqu ekhoyo kumanqamu emiphunga ahlukahluka kuxhomekeke kumhlobo womhlaza womphunga . I-EML4-ALK i-fusion genes zixhaphake kakhulu kubantu abanomdla wesifo somhlaza wesifo samangqamu omnxeba esithi lung adenocarcinoma . Oko kwathiwa, kwiimeko ezinqabileyo, i-ALK ifunyenwe kubantu abane- squamous cell carcinoma yemiphunga (enye uhlobo lomhlaza wesifo somhlaza wamangqamuzana) kunye nomdlavuza omncinci wamangqamuzana .
Kukho abantu abathile abanokuthi bafumane i-ALK yefusion geni. Oku kubandakanya izigulane ezincinci, abantu abangazange bavume (okanye bathe bancinci kakhulu), abafazi, kunye nalabo base-East Asian ubuhlanga . Kuhlolisiso lwakutshanje, kwafunyaniswa ukuba izigulane ezingaphantsi kweminyaka engama-40 zivavanywe kakuhle kwi-EML4-ALK i-fusion geni malunga neepesenti ezingama-50 zexesha (ngokuchasene nama-3 ukuya kuma-5 ekhulwini labantu bonke ubudala abanomdlavuza wamaphaphu.)
Ngubani omele ahlolwe i-ALK Mutation (Rearrangement)?
Imibutho emininzi isebenzisene kunye nokuphuhlisa izikhokelo malunga nobani kufuneka bavavanyelwe ukuguqulwa kwe-ALK. Isivumelwano sokuba zonke izigulane ezine-adenocarcinoma eziphambili kufuneka zihlolwe iinguqu ze-ALK kunye ne-EGFR, kungakhathaliseki ukuba isini, imbali yokutshaya, nezinye izinto ezibeka ingozi, kunye nohlanga.
Enye imingcele kukuba ezinye izicubu zinemimandla ebonakala ngathi iyimibala eyahlukeneyo yomhlaza wamaphaphu. Ngokomzekelo, izicubu kwelinye inxalenye ye-biopsy zinokubonakala ngathi i-adenocarcinoma kunye nezicubu kwelinye inxalenye yesampuli ye-biopsy inokubonakala ngathi ngumhlaza wesifo somhlaza wamangqamuzana.
Kukho ezinye iimeko ezingekho kwiingcali ezigqithisileyo. Ngokomzekelo, ukuvavanywa kunokucetyiswa kumntu ongazange atshe, nangona uhlobo lwawo lomhlaza wesifo samaphaphu alubonakali ukuba yi-adenocarcinoma. Ezi zikhokelo ziza kutshintsha njengoko zininzi ezifundwe malunga nale miguqulelo, kwaye ezinye izitshintsho zifunyenwe kwaye unyango olulandelayo luphuhlisiwe.
I-ALK I-Positive Lung Cancer Isenziwa Njani?
Nangona ukulungiswa kwe-ALK kumdlavuza wamaphaphu kwafunyanwa ngo-2007, unyango (okwangoku ezine) kubantu abanolu tshintsho (kunye nokuba nomdlavuza wamaphaphu) sele uvunyiwe yi-FDA. Imvume ye-FDA - kwiminyaka engama-4 kuphela emva kokufunyanwa kwe-rearrangement-inomdla phakathi kwimiqathango yonyango lwemiphunga yemiphunga engazange ikhule ngokunyanisekileyo kwiminyaka emininzi edlulileyo.
Masiqale ngokuthetha ngamachiza okuqala avunyelweyo, kwaye sithethe ngamachiza ezongezelelweyo ngoku sele avunyelwe abo banokulungiswa kwe-ALK
Usebenza njani ? Amachiza - i- Xalkori (crizotinib) iyimithi ye-tyrosine kinase. Kule meko, i-Xalkori ibopha kwi-receptor ye-tyrosine kinase ephezulu yamaseli omhlaza wamaphaphu kwaye inqanda iprotheni engavumelekanga. Indlela elula yokuyiqonda oku kukucinga nge-receptor ye-tyrosine kinase njengekhikhi, kunye neprotheni ye-tyrosine kinase (eyenziwe ngumgubo ongaqhelekanga) njengothixo. Abantu abanokuguqulwa kwe-ALK banokhiye olungavamile. Xa iqhosha "lifakwe," iimpawu zithunyelwa kwisikhungo sokukhula ukuba iiseli zihlukane ngaphandle kokuyeka. Imithi enjenge-Xalkori umsebenzi ngokuthintela isihluthulelo - uhlobo oluthileyo xa ugcwalisa isikhokelo kwimnyango wakho wangaphambili ngekhonkrithi. Ekubeni i-key (iprotheni engavumelekanga) ayikwazi ukungena kwi-lock (zibophe i-receptor,) umqondiso weseli ukwahlula kwaye ukhule ungafi ufike kwisikhululo sokulawula kunye nokwahlukana kweeseli (ukukhula kwe-tumor) kumisiwe.
Isebenza njani kakuhle? Uphando lufumene ukuba unyango kunye neXalkori lubangela ukuqhubekeka kokusasazeka kwee-7 ukuya kwiinyanga ezili-10. Kukho amazinga angama-50 ukuya kuma-60% okuphendula kwisilwanyana. Oku kungabonakali kukumangalisayo, ngakumbi xa kuthelekiswa nokunyanga kwamanye amachiza, kodwa kuyaphawuleka ukuba abantu kulezi zifundo sele befumene kwaye behlulekile ukuphefumula i-chemotherapy yangaphambili kunye nokulinganiselwa kwezinga lokuphendula ukunyusa i-chemotherapy yendabuko kuya kuba malunga ne-10% ngokomyinge ukusinda okungaqhubekiyo kokuqhubeka kweenyanga ezi-3.
Nangona izinga lokuphendula ne-Xalkori libhetele kunokuba i-chemotherapy esezingeni eliqhelekileyo, uphando alufumananga ukuba i-Xalkori iyandisa ukusinda jikelele . Sekunjalo ngelixa kubalulekile ukunyuka, umgangatho wobomi ubalulekile. Ukulahla ukuqhubela phambili komhlaza kunganciphisa impawu ezinxulumene nomhlaza, kwaye enyanisweni, izigulane eziphathwe nge-Xalkori zineempawu ezimbalwa ezinxulumene nomdlavuza wamaphaphu ( ukuphefumula okufutshane , intlungu yesifuba kunye nokukhathala.) Akuqinisekanga nokuba ngaba isifundo sifunde ngokuchanekileyo izinga lokusinda kuba abantu beli phofu bavunyelwe ukuba "badlule" kwaye basebenzise olunye unyango ukuba iimpawu zabo ziyaqhubeka. Abantu abaninzi bayeka ukhemotherapy kwaye batshintshela kwi-crizotinib kunenye indlela.
Ekubeni i-Xalkori ivunyiwe, ezinye iimyeza ziye zavunywa ukuba zonyango lwe-ALK-positive nomdlavuza wamaphaphu. Ezi ziquka:
- Zykadia (ceritinib)
- Alectinib (alencensa)
Ukongeza, isilwanyana esitsha ukujongana nomdlavuza we-ALK-positive, u-Alunbrig (brigatnib) uvunyiwe ngo-Apreli 28, 2017.
Ngexesha langokunje kucatshangelwa ukuba i-alectinib inikezela ngokuqhubekayo kokuhamba kwamahhala kunokuba i-crizotinib (iinyanga ezingama-25.7 vs 10,4 iinyanga) kwaye inemiphumo embalwa yecala. Oku kuthetha, kubalulekile ukuthetha ne-oncologist yakho malunga nawaphi kwezi ziyobisi eziza kusebenza kakuhle kuwe.
Kubalulekile ukukhumbula ukuba i-tyrosine kinase inhibitors ayilona unyango lomdlavuza wamaphaphu , kodwa kunoko into evumela ukuba i-tumor "igcinwe ingqwalasela" njengokuba imithi yesifo sikashukela ikwazi ukulawula eso sifo kodwa ayiyiphilisi. Kuthemba ukuba kwixesha elizayo, umhlaza wamaphaphu, ubuncinane iindidi ezithile kunye nokuguquka okuthile, kunokuphathwa njengezinye izifo ezingapheliyo ezifana nesifo sikashukela.
Ukuchasa
Ngelishwa, nangona isiqingatha sabantu siphendula kakuhle kunyango, ukuchasana kubakho rhoqo kuqhubeka kunye neyeza lilahlekelwa ngempumelelo. Kubantu abaphuhlisayo ukunganyangeki, kusekho iindlela ezikhoyo. U-Alectinib wanikezelwa ukuqulunqwa komsebenzi ngo-2013 kubantu abane-ARK-positive yomdlavuza wamaphaphu ekumelana ne-crizotinib. Ngo-Matshi ka-2014 enye iyeza-iZykadia (ceritinib) - inikwe unyango lolawulo lwe-FDA. Izinga lokuqala lokuphendula kwiZykadia zazifana nalabo abaneXalkori. Ukongezelela - abaninzi abantu abaye bachasene neXalkori baphendule kwiZykada. Amachiza amatsha afundiswa kwizilingo zekliniki kubantu abaphuhlisayo, kwaye abanye abaphandi banethemba lokuba kwiigulane zizayo ziyakuthi ziphathwe ngendlela elandelelanayo kunye nalezi yobisi njengoko ukunyanzelisa kuqhubeka.
Ukongezelela, izicubu zitshintsha rhoqo (ukuphucula utshintsho olutsha) ngokuhamba kwesikhathi. Ngamanye amaxesha unyango olujolise kwenye inguqu ephathekayo (efana ne-EGFR) inokusebenza nangona i-tumor yayingenakuqala ukuba iguqulwe ngo-EGFR. Kuthemba ukuba kwikamva elisondeleyo siya kuba nako ukunyanga umdlavuza wamaphaphu - ubuncinane le subtype - ngendlela efanayo ngendlela esiphatha ngayo ezinye izifo ezingapheliyo.
Yiyiphi Imithi Eyona Mhle?
Izilingo zezonyango ziqhubeka ngokuzama ukufunda kabanzi malunga nawaphi amayeza asebenzayo ngoku asebenza kakuhle. Kukho ubungqina bokuba iziyobisi ezitsha (zombini kunye ne-ALK rearrangements kunye nezinye izitshintsho) zinokukwazi ukuphucula bhetele i-metastas to the brain. Ngenxa yobungqina begazi-ingqondo, uchungechunge lwee-capillaries eziqiniweyo ezivimbela amanxuwa amaninzi (kuquka i-chemotherapy kunye neengxaki zonyango) ekungeneni kwengqondo, ezininzi iziyobisi esele zifumaneke ukunyanga umdlavuza wamaphaphu azisebenzi kakuhle i-metastases. Kulabo abaneengcali ezimbalwa zobuchopho, i-stereotactic brain radiotherapy (i-SBRT) okanye i-cyber knife inike ithuba lokunyanga oku, kodwa ngokufanelekileyo, kwixesha elizayo, siya kuba neyeza ezinokukwazi ukujongana nazo ezingcono.
Isilumkiso Ngokutya kweVitamin E
Sisoloko silumkisa abantu malunga nokuthatha nayiphi na isongezelelo ngexesha lonyango lomhlaza ngaphandle kokuqala ukuthetha ne-oncologist yabo, kwaye oku kubalulekile nge crizotinib (kwaye mhlawumbi nezinye iilathrapi). Ngo-2018 kwafunyanwa ukuba i-vitamin E ebizwa ngokuba yi-tocopherol inokuphazamisa ngokuphawulekayo unyango lwe-crizotinib. I-Vitamin E (okanye ubuncinci eli candelo) zombini yanciphisa umsebenzi we-crizotinib, kwaye ibuye ivimbele ukufa komhlaza wesifo ngenxa ye-crizotinib. Ibonakala ibonakala yinyaniso kwi-tocopherol, kwaye ayikho enye inxenye yevithamini E efana ne-y-tocopherol. Oko kwathiwa, ezininzi izithako ze-vitamin E kunye nezinye izithako ze-vitamin eziqukethe i-vitamin E zidla ngokuba ne-tocopherol njengesithako esibalulekileyo.
Iimiphumo eziPhezulu zonyango
Njengoko unyango oluninzi lomhlaza, amayeza anjengeXalkori aneempembelelo. Ngombulelo uninzi lwezi zinto zinzima kunezinto abantu abazenzayo kwi-chemotherapy yendabuko. Iimpawu eziqhelekileyo abantu abahlangabezana nazo kwi-Xalkori ziquka iingxaki ezibonakalayo, isifo sohudo, isisongela, ukuphefumla okufutshane, kunye nokuhlolwa okungaqhelekanga kwesilingo. Isiphumo esingaqabile kodwa esinamandla esiye saqatshelwa kukuphuhliswa kwesifo sengqondo somngcwabo esingaqhelekanga.
Ngelixa elizayo
I-ALK yefusion ye-fusion ingomnye weenguqu ezininzi ezikhoyo kumaseli omhlaza wamaphaphu. Kuthemba ukuba njengoko oku kuqondwa kangcono, unyango olutsha luya kufumaneka oluya kuthi lube luphikisana nokuchasa kodwa lujolise kwezinye izinto ezingaqhelekanga (utshintsho lomqhubi) kumaseli omhlaza. Ngokubhekiselele kwi-crizotinib, kucingelwa ukuba le nkunkuma inokubanceda abanye abantu abangenayo i-ALK yefusion ye-fusion kodwa banezinye izakhi zegesi ezinokungaqhelekanga (njenge- ROS1 rearrangement .)
Amazwana okugqibela
Ukuze amayeza asetyenziswe ekujoliswe kuwo atshintshe njenge-ALK, abantu abanomdlavuza wamaphaphu kufuneka bavavanyelwe ukuguqulwa. Ngelixa izikhokelo zincoma ukuhlolwa komntu wonke onomdlandla we-adenocarcinoma kwaye ukusetyenziswa kwale teknoloji kwanda, kusekho abantu abaninzi abangazange banikwe uvavanyo.
Kukho izizathu ezimbalwa zezi. Enye kukuba le ndawo iyashintsha ngokukhawuleza yamachiza, kwaye akukho dokotela onokuthi abe phezu kwayo yonke into entsha yokufumana. Buza imibuzo. Yenza uphando oluthile (okanye unomhlobo okanye umthandayo ucwaninga i-tumor yakho.) Cinga ukufumana umbono wesibini kwisiko somhlaza esibona umthamo omkhulu wegulane zomdlavuza wamaphaphu.
- Indlela Yokukhetha Isiko Sonyango Seengculaza
- Amanyathelo okuQala xa usandululwazi olutsha kunye neLung Cancer
- Indlela Yokuzivikela Ngomdlavuza
Enye inkathazo yindleko. Amachiza omtsha ajolise kwiimeko ezingekho phantsi kweeseli zeomhlaza zivame ukuza kunye nethegi lentengo. Kodwa kukho iindlela ezikhoyo. Kwalabo abangenayo i-inshorensi, kukho urhulumente kunye neenkqubo ezizimeleyo ezinganceda. Kwabo abanomshuwalense, iinkqubo zoncedo lwe-copay zingancedisa ukulahlekisa iindleko. Kwezinye iimeko, umenzi weziyobisi unokukwazi ukubonelela ngemishanguzo ngexabiso elincinci. Kwaye kubalulekile, nje ngokuba uthatha inxaxheba kwilingo leklinikhi , amayeza, kunye nokutyelela i-ofisi, zihlala zibonelelwa ngexabiso.
Njengengxelo yokugqibela, kungakhathaliseki ukuba ufunda kangakanani kwiqela lakho lezonyango, akukho nto injengeentetho ezivela kubantu abaye bakhona kwaye bafumene unyango oza kufumana. Khangela amaqela enkxaso kubantu abanomdlavuza wamaphaphu kwaye babuze ukuba ubani umntu onokuguqulwa kwe-ALK. Eminye imibutho efana neLUNGevity ineenkonzo ezifanayo (i-LUNGevity LifeLine) apho ziyakwazi ukufanisa nomntu onomdlavuza wamaphaphu onalo uhlobo olufanayo kunye nesigaba sesisu.
> Imithombo:
> Umbutho waseMerika woPhando lweCancer. Iziphumo ezintsha zokufumana iiDovu ezivulekileyo kwiiNgcaciso zonyango lwe-Lung Cancer. 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. IiNqoloba zePathology kunye neeLayibrari . 2012. 136 (10): 1201-4.
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> I-Garber, K. ALK, umdlavuza weLung, kunye noTyhutyana loLuntu: iNgxelo yexesha elizayo? . Umbhalo weNational Cancer Institute . 2010. 102 (10): 672-675.
> Katayama, R. et al. Iinkqubo zoxhathozo lwe-crizotinib kwi-ALK-i-re-edited cancer cancers. Inzululwazi yokuguqulela isayensi . 2012. 4 (12): 120ra17.
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