Ukuqonda kabusha i-ROS1 Gene Rearrangement ku-Can-Small Cell Lung Cancer
Ukuhlelwa kabusha kwe-ROS1 kuyinto engavamile ku-chromosome engaba khona emangqamuzaneni omdlavuza njengamaseli omdlavuza wamaphaphu. Ama-Chromosomes-kanye namajesenti akha ama-chromosomes ethu-athatha ikhodi yezinto ezifana nombala wamehlo ethu. Bafaka ikhodi (yenza njengendlela yokuhlela) amaprotheni alawula ukukhula nokwahlukana kwamaseli. Uma enye yalezi zakhi zofuzo noma ama-chromosomes ewonakele, eguqulwa, noma ehlelwa kabusha, ikhodiza iphrotheni engavamile, engenza imisebenzi engavamile, njengokushayela ukukhula komdlavuza.
Indlela yokucabangela isakhi kufanele ucabange uchungechunge lwezinhlamvu ezikhuluma amagama. Uma lezi zincwadi zixubene, amagama aphuma angalungile. Uma ama-gciwane ku-chromosome ahlelwa kabusha emaphethini ahlukene, amagama aphuma angalungile futhi. Uma uzwa inkulumo ethi "ukudluliselwa kwezakhi zofuzo," lokhu kusho ukuthi izinhlamvu ze-ROS1 zegene zihlanganiswe ngokungavamile kwesinye isakhi, futhi kuholela ekuhlanganiseni kulokho okushiwo "izinhlamvu".
I-ROS1 Rearrangement ye-Gene
Akuzona zonke izakhi zofuzo nezinguquko ezilinganayo. Enye ikhodi yama-protein enza njengabashayeli. Amakhodi we-ROS1 wephethini weprotheyini esebenza njengomshayeli yinye engakwazi ukuqhuba umbukiso uma kuziwa ekukhuleni kwamaselula nokuhlukana. Uma isakhi sakhiwe kabusha, amaprotheni angavamile angenza ukukhula okungavamile nokuhlukaniswa kweseli.
Le protheyini ingenye yamaprotheni (ama-enzyme) eyaziwa ngokuthi i-tyrosine kinases. Lawa maprotheni athumela izibonakaliso esikhungweni sokukhula esitokisini ukukwazisa ukuthi nini ukwahlukanisa nokwanda.
Ukulungiswa kabusha kwe-ROS1 kuze kube manje kutholakale kuphela kubantu abanomdlavuza we-cell wamaphaphu okungewona omncane futhi, ngalolu hlobo, abantu kuphela abane- lung adenocarcinoma . Ayitholakalanga kubantu abaguqule ku-EGFR noma i-KRAS noma i-ALK rearrangements.
Uma kuqhathaniswa nezinye izinhlobo zomdlavuza wamaphaphu, isifundo se-2015 sathola ukuthi:
- Isikhathi esiphakathi kwabantu abane-ROS1 rearrangements kwaba ngu-50.5. (Isikhathi esiphakathi komdlavuza wamaphaphu , ngokuvamile, singu-72.)
- Kwakujwayelekile kakhulu kwabesifazane ukuthi amaphesenti angu-64.5 ayengabesifazane. (Umdlavuza wamangqamu kumadoda uvame kakhulu kunabesifazane.)
- Amaphesenti amakhulu-amaphesenti angu-67.7-ayengabhemi ngaso sonke isikhathi. (Kanti umdlavuza wamangqamu kwenzeka ngokungabikho ababhemayo, okungenani amaphesenti angu-20 emdlavuza wamaphaphu kulabo besifazane abangabokubhema.)
- Kuphuma kubantu abane-lung adenocarcinoma, amaphesenti angu-3.1 abe nokuhlelwa kabusha kwe-ROS1.
Ukubuza ukuthi ngabe i-tyrosine kinase inhibitor esebenza yini enye isifo somdlavuza we-rearrangement-umaphaphu ene-ALK-rearrangement noma umdlavuza wamaphaphu we-ALK- ingasebenza ukuvimbela imiphumela yeprotheni engavamile eyenziwa yi-ROS1 ehleliwe kabusha? Abacwaningi bazama imithi esetshenziswe ngempumelelo kubantu abane-ALK-positive yomdlavuza wamaphaphu. Okumangalisa ukuthi kwasebenza nomdlavuza we-ROS1 omuhle kakhulu nakakhulu.
Ukuhlolwa kokuxilongwa
Kunezindlela ezimbalwa lapho abantu abanomdlavuza wamaphaphu bangahlolwa khona ukuze babone ukuthi bane-ROS1 yokuhlelwa kabusha. Isivivinyo senziwa esikhwameni sesishukela kusuka ekuhlinzekeni komdlavuza we-lungs noma umdlavuza wamaphaphu. Kuthemba ukuthi ekuhlolweni okuzayo kuyotholakala nge-biopsy ye-liquid-isilingo esenziwe ngegazi esingatholakala nge-draw elula yegazi.
Izindlela zokuhlola zifaka i-immunohistochemistry kanye ne-fluorescence in hybridation situ (FISH). Izifundo ziyaqhubeka ukuze zithole izindlela ezinhle zokuhlola.
Njengoba abantu abane-ROS1 rearrangements abanalo ukuguqulwa kwe- KRAS no- EGFR noma ukulungisa kabusha kwe-ALK (okungenani hhayi ekuvivinyweni okwenziwe kuze kube yimanje,) ukuhlolwa kuvame ukwenza kubantu abangalungile kulezi zinguquko nokuhlelwa kabusha. Ungase uzwe lokhu okukhulunywe ngokuthi "umdlavuza wamaphaphu wamangqamuzana omncane" ongeyena omncane, hhayi ukudideka nomdlavuza wesifuba kathathu ongeke uhluke ngokuphelele. Kwesinye isifundo, kwafunyanwa ukuthi, ngaphandle kweziguli ezivivinywe kabi nge-KRAS ne-EGFR, amaphesenti angu-25 ayelungele i-ALK noma i-ROS1 i-fusion yegene.
Kucatshangwa ukuthi noma ubani onomdlavuza wesifo samangqamuzana ongewona omncane, ikakhulukazi i-lung adenocarcinoma, kufanele abe nokuhlolwa kofuzo (ukuprofethwa kwamangqamuzana) okwenziwe emathunjini abo emaphaphu. Ukuhlola kubaluleke kakhulu kubantu abasha abanomdlavuza wamaphaphu , abanezimo eziphezulu zokuguqulwa kwezifo futhi bangase baphendule kahle eminye imithi esesigaba se-tyrosine kinase inhibitors. Ngaphezu kwalokho, kubaluleke kakhulu ukuthi ababhemayo abangeke bahlolwe kwenziwe, njengalabo abangabhemi ababhemayo kukhona izigameko eziphezulu zokuguqulwa kwezinguquko nokuhlelwa kabusha.
I-ROS1 I-Cancer Positive Lung
Umdlavuza we-ROS1 omuhle lungumzimba wamaphaphu ovivinya ukulungiswa kabusha kwe-ROS1, enye yezinto eziwaziwa ngokuthi "izinguquko zomshayeli" ezitholakala emdlavuza wamaphaphu. I-ROS1 emihle yomdlavuza wamaphaphu i-akhawunti yamaphesenti amabili kuphela kwamaphesenti amabili wamaphaphu emaphaphu. Kodwa, uma sicabangela ukuthi umdlavuza wamaphaphu ovamile ungakanani, usabamelela abantu abaningi abanalesi sifo.
Ukulungiswa kabusha kwe-ROS1 kutholakala okokuqala ku-glioblastoma multiforme, uhlobo lomdlavuza webuchopho, futhi kutholakale kwezinye izifo zomdlavuza, kuhlanganise nomdlavuza we-ovari, i-colorectal carcinoma, umdlavuza wesisu kanye ne-cholangiocarcinoma.
Kubalulekile ukugcizelela ukuthi uhlobo lokuhlelwa kabusha kwezakhi zofuzo esikukhulumayo ngushintsho oluthile lwezakhi zofuzo. Ngokungafani nokushintshashintsha kwezakhi zofuzo kanye nokuhlelwa kabusha kwezinto abantu abazalelwa ngazo, ezinye zazo ezingabangela abantu ukuba babe nomdlavuza, i-ROS1 ye-rearrangement yegciwane ayikho kusukela ekuzalweni. Akudingeki ukhathazeke ngokuthi izingane zakho zizozuza i-rearrangement.
Ukwelapha
- Ukuhlinzwa -Ngabantu abanesiteji ngiya esiteji IIIA, ukuhlinzwa komdlavuza wamaphaphu kungaba yindlela yokukhetha. Akuzona zonke izicubu zalezi zigaba ezisebenzayo, kodwa uma zikhona, ukuhlinzwa kunganikeza ithuba lokuthola ukwelashwa.
- I-Chemotherapy -Kukhona ukwelapha okuhlosiwe, amanye ama-chemotherapy agents nawo aphumelelayo ku-ROS1 izicubu ezinhle. Umdlavuza wamaphaphu we-ROS1 ubonakale uzwela kakhulu kumuthi we-chemotherapy u-Alimta (pemetrexed) onamaphesenti angaphezu kwangu-50 abantu abaphendula izidakamizwa ocwaningweni olulodwa.
- Imithi ehlosiwe -Xalkori (crizotinib) yi-inhibitor ye-tyrosine kinase eyayivunyelwe ekuqaleni komdlavuza we-ALK-positive. Kunconywa umugqa owokuqala-okungukuthi, ngaphambi kwanoma yiziphi ezinye izindlela zokwelashwa (nakuba ezinye izifo zingasetshenziswa ngesikhathi esifanayo) kanye nanoma ubani oye waphatha ukwelashwa ngaphambi kwalesi sifo. Le mithi yamukelwa umdlavuza wamaphaphu we-ALK ngo-2013 futhi wadala injabulo ngokuhamba kwesikhathi lapho ukuhlolwa kwesigaba sesi-I nabantu abane-ROS1 yomdlavuza wamaphaphu waphendula kangcono nakakhulu kumuthi. Kulezi zivivinyo zomtholampilo, inani labantu abaye basabela kulo muthi laliphakathi kwamaphesenti angu-70 no-80. Isidakamizwa sanikezwa ukwelashwa okubizwa ngokuthi i-ROS1 emihle ngo-Ephreli ka-2015. I-Loratinib uma ivunyiwe kulabo abanomdlavuza othuthukile ku-Xalkori. I-Ignyta (entretinib) ayifuni ukusebenza kulabo i-Xalkori ayiphumelelanga, kodwa ingaba usizo kulabo abanezinkinga zokuphefumula.
- Ukuhlolwa kwemitholampilo -Eminye imithi, ikakhulukazi ekuhloswe ngayo imithi yokwelapha, isacwaningwa ekuhlolweni kwemitholampilo kubantu abane-ROS1 emihle yomdlavuza wamaphaphu. Ezinye zazo zihlanganisa iZykadia (ceritinib), esinye isidakamizwa esifana ne-crizotinib evunyelwe umdlavuza wamaphaphu we-ALK. Eminye imishanguzo efundiswa ngamagciwane e-lung amaphaza avuselelwe kabusha i-ROS1 afaka i-Cometriq (cabozantinib) nabanye. Ukuze ufunde kabanzi mayelana nokuhlolwa kwemitholampilo yomdlavuza wamaphaphu, cabanga ngokuxhumana nesevisi yokulinganisa imitholampilo yamahhala etholakala kuzo zonke iziguli zomdlavuza wamaphaphu.
I-Brain Metastases
I-ROS1 emihle yamaphaza emaphaphu avame ukusabalalisa ebuchosheni. Kulinganiselwa ukuthi amaphesenti angu-25 kuya kuma-40 amaphesenti abantu ababhekene nomdlavuza ongasona omncane wamaphaphu azokwakhiwa kwe-metastase yobuchopho phakathi neminyaka emibili yokuqala yokwelapha.
Ngeshwa, i-Xalkori (crizotinib) ayisebenzisi kahle kakhulu kumetastases ebuchosheni kubantu abane-ROS1 emihle yomdlavuza wamaphaphu. Le mithi, njengabaningi, ayiweleli kahle imingcele yegazi-yobuchopho . Isivinini segazi-ingqondo yisimiso sokulawula sezinambuzane ezikhethekile ezisebenza ukuvimbela ubuthi (kanye nezidakamizwa zamakhemikhali) ukungena endaweni ezwelayo ebuchosheni.
Ukwelashwa kwezidakamizwa ze- metastase ebuchosheni kubantu abanomdlavuza wamaphaphu bangasebenza kahle. Futhi kutholakale ukuthi abantu abane-ROS1 rearrangements banezicubu ezingahle zizwele kakhulu kulezi zindlela zokwelashwa. I-radiation inganikezwa ngezindlela ezimbalwa ezihlukene:
- I-radiotherapy e-stereotactic -Kulendlela , ongayizwa ebizwa ngokuthi "i-cyberknife" noma ummese we-gamma, ukukhishwa kwemisebe kunikelwa ezindaweni ezisezindaweni zobuchopho.
- Ukuphefumula okuphelele kwe-radiotherapy -Ukuphela kokwelashwa kwama-radiation onke, lonke ubuchopho buphathwa nge-radiation.
Ukuzikhethela phakathi kwalezi zindlela ezimbili kuyindawo yokuphikisana. I-radiotherapy-stereotactic-ngoba ithinta kuphela ingxenye encane yobuchopho-inezimbangela ezimbalwa. Kodwa-ke, ubuchopho obuchopho be-radiotherapy bunganciphisa ithuba lokuphindaphinda kobuchopho-into ejwayelekile kakhulu kubantu abaye babhekana ne-metastases yobuchopho kakade.
Inani le "amabala" nalo lidlala indima kule sinqumo. Abantu abanezintambo ezimbalwa kuya kwezingu-4 noma ezine-baphathwa kalula ngendlela ye-stereotactic kunelabo abanamathenda amaningi.
Ukuphikiswa Kwemithi
Iningi labantu ekugcineni liyakwazi ukumelana ne-Xalkori (crizotinib) ngenxa yokushintshwa okusha okusha. Imithi emisha kuleso sigaba, iCometriq (cabozantinib), ivela ngokuthembisayo kakhulu ekufundeni kokuqala. Kubonakala sengathi uyakwazi ukunqoba ukuphikiswa kusuka kulezi zinguquko ezincane ezifundweni zakuqala.
Ukuqapha Ngokuphathelene ne-Vitamin E ne-Crizotinib
Izifundo ngo-2017 no-2018 ziphakamisa ukuthi ingxenye ye-vitamin E ebizwa ngokuthi i-tocopherol inganciphisa kakhulu ukusebenza kwe-crizotinib. Njengoba amavithamini amaningi e-vitamin E, kanye namavithamini aqukethe i-vitamin E engxenyeni noma ikakhulukazi i-tocopherol, lezi zithako kufanele zigweme ngaphandle kokuthi zichazwe ngokuqondile nge-oncologist yakho.
Isibikezelo
I-ROS1 emihle yamaphaza emaphaphu athambekele ekubeni nobudlova futhi akhule futhi asakaze ngokusheshisa, kodwa futhi aphendule ngendlela engakaze ibe khona yokuthola ukwelashwa okuhlosiwe. Njengoba ukwelashwa kusanda kuvunyelwa, kunzima ukwazi ukuthi isikhathi somuntu sokuphila siyoba yini. Kodwa, izimpendulo ezibonwe kuze kube manje ziyakhuthaza.
Esikhathini esisodwa isifundo isikhathi esiphezulu sesikhathi u-Xalkori asebenze (isikhathi esilandelayo sokuyeka ukusebenza kwesigamu sabantu kodwa saqhubeka nokusebenza ingxenye enye) kwakuyizinyanga ezingu-17; iningi labantu baphathwe baphendule kulo muthi.
Kuthemba ukuthi lapho abantu beba nomelana nalo muthi abanye abazoba khona, bavunyelwe, noma ekuvivinyweni kemitholampilo okungase kube khona esikhundleni somuthi oyeke ukusebenza. Njengoba kuphawuliwe, kunezibonakaliso ukuthi lokhu kungase kube njalo.
Esikhathini esizayo esiseduze, ngethemba lokuthi umdlavuza wamaphaphu nalezi zinguquko kanye nokuhlelwa kabusha kuzophathwa njengezifo ezingapheli, njengokuthi siphatha kanjani isifo sikashukela. Ngisho noma umdlavuza ungakapholakali, ngokuqinisekile uzobe ulawula.
Ukusekela kanye nomphakathi
Iqembu elihle labantu abanomdlavuza wamaphaphu omuhle we-ROS1 bahlangene ndawonye. I-ROS1Ders ixhumane nokusheshisa ucwaningo ekwelapheni kwezilonda ezihle ze-ROS1. Njengoba lokhu kungumlando wamangqamuzana ongajwayelekile kakhulu we-tumor, abaningi be-oncologists emphakathini abajwayele ucwaningo lwamuva kanye nezivivinyo zomtholampilo ezitholakalayo. Esizeni sabo sinezixhumanisi zabahlengikazi abaphezulu nabacwaningi abacwaninga umdlavuza wamaphaphu omuhle we-ROS1 uma udokotela wakho efisa ukubonisana nomuntu enhliziyweni yocwaningo. I-Global ROS1 Initiative yubambiswano oxhumanisa abacwaningi, iziguli, abanakekeli, kanye nodokotela emhlabeni jikelele ukuthuthukisa imiphumela yeziguli nokusheshisa ucwaningo.
Izwi elivela
Akekho okufanele ahambe nomdlavuza wamaphaphu yedwa. Uma othandekayo wakho etholakele ukuthi unomdlavuza wamaphaphu, hlola le mibono mayelana nokuthi umthande wakho unomdlavuza wamaphaphu .
Ukubandakanya emphakathini womdlavuza wamaphaphu kungase kube usizo kakhulu, ngisho nalabo abavame ukugwema amaqembu. Njengoba umdlavuza wamaphaphu omuhle we-ROS1 ungavamile, akunakwenzeka ukuthi uzothola abantu abaningi emphakathini wakho ababhekana nezinselele ezifanayo zomzimba nezomzwelo.
Ngonyaka ka-2015, eNgqungqutheleni ye-LUNGevity HOPE, iqembu elakhiwe kuphela labantu ababhekene nomdlavuza we-ROS1 omuhle wamaphaphu. Lesi yisikhathi esijabulisayo kubantu abanomdlavuza wamaphaphu, njengoba iziguli zisebenza ngokuhlangene nodokotela hhayi kuphela ukuqonda isifo sabo, kodwa ukunikeza okokucwaninga okusadingeka kwenziwe.
Imithombo:
UDavare, M., uSaborowski, A., Eide, C. et al Foretinib uyisimiso esinamandla sama-protein ane-fusion e-oncogenic. Izinqubo ze-National Academy of Sciences yase-United States of America . 2013. 110 (48): 19519-24.
UDrilon, A., Somwar, R., Wagner, J. et al. I-novel crivatinib-resistance resistant-solvant-front mutation isabela ekwelashweni kwe-cabozantinib esigulini nomdlavuza we-ROS1-kabusha we-lung. Ucwaningo lweCancer Clinic . 2015 Dec 16.
UKayayama, R., Kobayashi, Y., Friboulet, L. kanye a. I-Cabozantinib inqoba ukumelana kwe-crizotinib ku-ROS1 umdlavuza we-fusion-positive. Ucwaningo lweCancer Clinic . 2015. 21 (1): 166-74.
ULukas, R., Hasan, Y., uNicholas, M., noRargia. I-ROS1 ehlelwa kabusha umthamo wesifo samangqamuzana omaphaphu wesifo samaphaphu ubuchopho be-metastases buyela emzimbeni ophansi we-radiotherapy. I-Journal ye-Clinical Neuroscience . 2015. 22 (12): 1978-9.
Mazieres, J., Zalcman, G., Crino, L. et al. Ukwelashwa kwe-crizotinib kwephamen adenocarcinoma ephuthumayo nokulungiswa kabusha kwe-ROS1: imiphumela evela eqenjini le-EUROS1. I-Journal ye-Clinical Oncology . 2015. 33 (9): 992-9.
Sequist, L, noJeal Neal. Ngokomuntu siqu, ukwelashwa okuqondiswe nge-genotype komdlavuza ongaphambilini omncane wesifo samaphaphu. Kusesikhathini. 01/12/16.
Shaw, A., Noma, S., Bang, Y. et al. I-Crizotinib ku-ROS-1 ihlelwe kabusha umdlavuza wamaphaphu ongewona omncane. I-New England Journal of Medicine . 2014. 371 (21): 1963-71.
USolomon, B. Ukuqinisekisa ukulungiswa kabusha kwe-ROS1 njenge-Target yezokwelapha ku-Can-Small-Cell Cell Lung Cancer. I-Journal ye-Clinical Oncology . Ngo-February 9, 2015.
> Uchihara, Y., Kidokoro, T., Tago, K. et al. Ingxenye enkulu yeVithamini E, i-Tocopherol ivimbela umsebenzi wokulwa nokuhlukumeza we-Crizotinib Amaseli aguqulwe yi-EML4-ALK. Journal European of Pharmacology . 2018 Feb 11. (Epub ngaphambi kokuphrinta).