Kumvetsetsa ROS1 Gene Rearrangement mu Can-Small Cell Lung Cancer
Kukonzekera kwa ROS1 ndilosazolowereka mu chromosome yomwe ikhoza kuchitika m'maselo a kansa monga maselo a kansa yamapapo. Chromosomes-ndi majeremusi omwe amapangidwa ndi ma chromosomes-amanyamula mfundo za zinthu monga mtundu wa maso athu. Amakhalanso ndi ndondomeko (chitani ngati ndondomeko) kwa mapuloteni omwe amayang'anira kukula ndi kugawanika kwa maselo. Pamene imodzi mwa majini kapena ma chromosome amaonongeka, amasinthidwa, kapena ayambiranso, amalemba puloteni yosadziwika bwino, yomwe imatha kuchita ntchito zosalongosoka, monga kuyendetsa kukula kwa khansa.
Njira yoganizira za jini ndiyo kulingalira makalata angapo omwe amatanthauzira mawu. Pamene makalata awa akusokonezeka, mawu amachokera molakwika. Ngati majeremusi pa chromosome agwiritsidwa ntchito mosiyana, mawuwa amatuluka molakwika. Ngati mumva mawu akuti "gene translocation," izi zimangotanthauza kuti makalata a jini la ROS1 amadziphatika mosavuta ku jini lina, ndipo amachititsanso kusakaniza zomwe zilembozo "spell."
ROS1 Gene Rearrangement
Sikuti kusintha konse kwa majini ndi kukonzanso zofanana ndizofanana. Makhalidwe ena a mapuloteni omwe amachita ngati madalaivala. Mthendayi ya ROS1 imakhala ndi mapuloteni omwe amachititsa dalaivala ndi imodzi yomwe ingakhoze kuyendetsa masewerowa pa kukula kwa maselo ndi magawano. Pamene jini ikonzedwanso, mapuloteni osadziwika angayendetse kukula ndi kusagawanika kwa selo.
Mapuloteniwa ndi amodzi mwa mapuloteni ambiri omwe amadziwika kuti tyrosine kinases. Mapuloteniwa amatumiza chizindikiro ku chipinda cha kukula kwa selo kuti chidziwitse nthawi yogawa ndi kuchulukitsa.
Kukonzekera kwa ROS1 mpaka pano kwapezeka kokha mwa anthu omwe ali ndi khansa ya m'mapapo yopanda maselo ndipo, mwa mtundu uwu, ndi anthu okha omwe ali ndi mapapu adenocarcinoma . Sipanapezeke mwa anthu omwe asintha mu EGFR kapena KRAS kapena ALK rearrangements.
Poyerekeza ndi mitundu ina ya khansa ya m'mapapo, phunziro la 2015 linapeza kuti:
- M'badwo wapakatikati wa anthu okhala ndi RAR1 rearrangements anali 50.5. (M'badwo wapakati wa khansa ya mapapo , ambiri, ndi 72.)
- Zinali zofala kwambiri kwa amayi mu 64.5 peresenti anali akazi. (Khansa ya m'mimba mwa amuna ndi yofala kwambiri kuposa akazi.)
- Ambiri peresenti-67.7 peresenti-sanali osuta konse. (Khansa yam'mimba imapezeka mwa osuta fodya, ndi khansa ya m'mapapo ya 20% mwa amayi omwe sakhala osuta fodya.)
- Kuchokera kwa anthu omwe ali ndi mapapo adenocarcinoma, 3.1 peresenti anali ndi kukonzanso kwa ROS1.
Akudabwa ngati tyrosine kinase inhibitor yomwe imagwira ntchito ya khansa yowonongeka-jekeseni yamapiritsi yokhala ndi khansa ya ALK kapena khansa ya m'mapapo ya ALK- ingagwiritse ntchito kuteteza zotsatira za mapuloteni osadziwika omwe amapangidwa ndi RNA1 yeniyeni? Chabwino, ofufuza anayesa mankhwala omwe agwiritsidwa ntchito bwino kwa anthu okhala ndi kansa ya m'mapapo ya ALK. Chodabwitsa n'chakuti, ntchitoyi inagwira ntchito kwambiri kwa khansa ya m'mapapo ya ROS1.
Kuyesa Kuzindikira
Pali njira zingapo zomwe anthu omwe ali ndi khansara yamapapu angathe kuyesedwa kuti awone ngati ali ndi rearrangement ya ROS1. Kuyezetsa kumachitika pazitsanzo za minofu kuchokera ku opaleshoni ya khansa yamapapu kapena mapapu. Akuyembekeza kuti kuyesedwa kwa mtsogolo kudzakhala kupezeka kudzera mu madzi akumwa-mayesero ochitidwa pa magazi omwe angapezeke ndi kutengeka kwa magazi.
Njira zopewera zikuphatikizapo immunohistochemistry ndi fluorescence in situ hybridization (Nsomba). Kafukufuku akupitirizabe kudziwa njira zabwino zopesera.
Popeza anthu omwe ali ndi rearrangements alibe KRAS ndi EGFR kusintha kwapadera kapena ALK rearrangements (osayesedwa poyesedwa mpaka pano,) kuyesedwa kawirikawiri kumachitidwa kwa anthu omwe ali olakwika chifukwa cha kusintha kumeneku ndi kusintha. Mungamve izi zatchulidwa kuti "khansa ya m'mapapo yowonongeka" yomwe siing'ono yaing'ono, osasokonezeka ndi kansa yachitatu yomwe imakhala yovuta kwambiri. Mu kafukufuku wina, anapeza kuti, kuchokera kwa odwala amene anayesera zoipa kwa KRAS ndi EGFR, 25 peresenti inali yabwino kwa ALK kapena ROS1 fusion gene.
Zimaganizidwa kuti aliyense amene ali ndi khansa ya m'mapapo yopanda mapapu, makamaka mapapu adenocarcinoma, ayenera kukhala ndi mayeso a maumunthu (mapulogalamu a ma maselo) omwe amachitidwa pamatumbo awo. Kuyesera n'kofunika kwambiri kwa achinyamata akuluakulu a khansa ya m'mapapo , omwe ali ndi chiwerengero chachikulu cha kusintha kwa mankhwala omwe angachiritsidwe ndipo akhoza kuwayankha bwino mwa mankhwala omwe ali m'gulu la tyrosine kinase inhibitors. Kuwonjezera apo, ndikofunika kuti osuta fodya ayesedwe, monga pakati pa osuta fodya pali kusintha kwakukulu kwa kusintha ndi kusintha.
ROS1 Positive Lung Cancer
Khansara yamapapu ya ROS1 ndi mapaipi a mapapu omwe amayesa zowonongeka kwa ROS1, yomwe imadziwika ndi "kusintha kwa kayendetsedwe ka galimoto" komwe imapezeka mu khansa ya m'mapapo. Nthenda ya kansa yamapapu yabwino ya ROS1 ndi gawo limodzi lokha pa magawo awiri a khansa ya m'mapapo. Koma, poganizira momwe kansa ya m'mapapo imagwirira ntchito, imakhala ikuyimira anthu ambiri omwe ali ndi matendawa.
ROS1 rearrangements anapezeka koyamba mu glioblastoma multiforme, mtundu wa khansara ya ubongo, ndipo anapezekaponso mu khansa zina, kuphatikizapo khansa ya ovarian, colorectal carcinoma, kansa ya m'mimba, ndi cholangiocarcinoma.
Ndikofunika kutsimikizira kuti mtundu wamasinthidwe amtundu womwe tikukamba nawo ndi kusintha kwa chibadwa. Mosiyana ndi kusintha kwa majini ndi kusintha kumene anthu amabadwa nawo, ena mwa iwo omwe amatha kuwapangitsa anthu kukhala ndi khansa, rejrangement ya ROS1 siyiyonse kuchokera kubadwa. Simuyenera kudandaula kuti ana anu adzalandira kukonzanso.
Chithandizo
- Kuchita Opaleshoni - Pakuti anthu omwe ali ndi masewera a pulasitiki ine ndikuyendetsa gawo la IIIA, opaleshoni ya khansa ya m'mapapo ikhoza kusankha. Sizitsulo zonse zazigawozi, koma zikachitika, opaleshoni ikhoza kupereka chithandizo.
- Chemotherapy -Zophatikizapo mankhwala opatsirana, mankhwala ena a chemotherapy amagwiranso ntchito pa zotupa za ROS1 zabwino. Khansa yabwino ya ROS1 yamapapu imapezeka kuti imakhala yovuta kwambiri ku mankhwala a chemotherapy Alimta (pemetrexed) ndi oposa 50 peresenti ya anthu omwe amamvera mankhwalawa mu phunziro limodzi.
- Njira zochiritsira -Xalkori (crizotinib) ndi tyrosine kinase inhibitor yomwe poyamba inavomerezedwa ku khansa ya m'mapapo ya ALK. Ndibwino kuti mzere woyamba ukhalepo, musanayambe mankhwala ena (ngakhale mankhwala ena angagwiritsidwe ntchito nthawi yomweyo) komanso kwa wina aliyense amene adalandira chithandizo chamankhwala kuchipatala. Mankhwalawa anavomerezedwa ku khansa ya m'mapapo ya ALK mu 2013 ndipo anasangalala kwambiri pakapita nthawi pamene mayesero a chipatala a phase 1 ndi anthu omwe ali ndi kansa ya m'mapapo ya ROS1 anachita bwino kuposa mankhwalawa. Mu mayesero awa, chiŵerengero cha anthu omwe adayankha mankhwalawa chinali pakati pa 70 ndi 80 peresenti. Mankhwalawa anapatsidwa mankhwala opatsirana pogwiritsa ntchito mankhwala opatsirana a kansa ya ROS1 mu April chaka cha 2015. Loratinib ngati ikuvomerezedwa kwa omwe khansara yakula pa Xalkori. Ignyta (entretinib) safuna kugwira ntchito mwa iwo omwe Xalkori walakwitsa, koma angakhale othandiza kwa iwo omwe ali ndi masewera a ubongo.
- Zilonda zachipatala - Zina mwa mankhwala, makamaka zokhudzana ndi zamankhwala, zikuphunziridwa m'mayesero azachipatala kwa anthu omwe ali ndi khansara yamapapo ya ROS1 yabwino. Zina mwa izi ndi Zykadia (ceritinib), mankhwala ena ofanana ndi crizotinib omwe amavomereza khansa ya m'mapapo ya ALK. Mankhwala ena omwe akuphunziridwa ndi khansa yamapapu amavomereza kuti ayambe kukonzanso ROS1 monga Cometriq (cabozantinib) ndi ena. Kuti mudziwe zambiri za mayesero a kachipatala a khansara yamapapo, ganizirani kuyanjidwa kwaufulu kwa kachipata komwe kulipo odwala khansa ya m'mapapo.
Matenda a ubongo
Matenda a khansa opatsirana a ROS1 amatha kufalikira ku ubongo. Zikuoneka kuti 25 peresenti kwa 40 peresenti ya anthu omwe amapezeka ndi khansa yaing'ono ya m'mapapo ya m'mapapo, imakhala ndi ubongo wa ubongo mkati mwa zaka ziwiri zoyambirira za chithandizo.
Mwamwayi, Xalkori (crizotinib) sagwira ntchito bwino kwa metastases ya ubongo kwa anthu omwe ali ndi khansara yokha ya ROS1 yabwino. Mankhwalawa, ochuluka, samatsutsana kwambiri ndi vuto la magazi-ubongo . Mitsempha ya ubongo ndi ubwino wa mankhwala omwe amathandiza kupewa poizoni (kuphatikizapo chemotherapy mankhwala) kuti asalowe mu ubongo.
Thandizo la mazira kwa metastase ku ubongo mwa anthu omwe ali ndi khansara yamapapu angathe kugwira ntchito bwino. Ndipo zapezeka kuti anthu okhala ndi ROS1 rearrangements ali ndi zotupa zomwe zingakhale zogwirizana kwambiri ndi mankhwalawa. Mafunde angaperekedwe m'njira zosiyanasiyana:
- Kachilombo ka radiotherapy - Mwa njira iyi, yomwe mungamve kuti "cyberknife" kapena mpeni wa gamma, kutentha kwa dzuwa kumaperekedwa kumalo amodzi mu ubongo.
- Ubongo wonse wotchedwa radiotherapy -Kodi mankhwala onse a ubongo amachititsa ubongo, ubongo wonse umachiritsidwa ndi dzuwa.
Kusankha pakati pa mankhwala awiriwa ndi malo otsutsana. Radiyo yotchedwa radiotherapy-chifukwa imangotenga mbali yochepa chabe ya ubongo-imakhala ndi zotsatira zochepa. Komabe, ubongo wa radiotherapy wonse ukhoza kuchepetsa mpata wochuluka wa metastases ubongo-chinthu chofala kwambiri kwa anthu omwe ali ndi metastases ya ubongo kale.
Chiwerengero cha "mawanga" chimathandizanso pa chisankho ichi. Anthu omwe ali ndi masewera atatu kapena anayi-amachiritsidwa mosavuta ndi njira ya stereotactic kusiyana ndi omwe ali ndi mavitamini ambiri.
Kukaniza Mankhwala
Anthu ambiri potsiriza amakhala otsutsana ndi Xalkori (crizotinib) chifukwa cha kusintha kwatsopano kumeneku. Mankhwala atsopano m'gulu lino, Cometriq (cabozantinib), akuwoneka kuti akudalira kwambiri pa maphunziro oyambirira. Zikuwoneka kuti zimatha kugonjetsa kutsutsana ndi kusintha kwachiwiri kumaphunziro oyambirira.
Chenjezo Ponena za Vitamini E ndi Crizotinib
Maphunziro mu 2017 ndi 2018 amasonyeza kuti chigawo china cha vitamini E chotchedwa-tocopherol chingachepetse mphamvu ya crizotinib. Popeza kuti vitamini E yowonjezereka, komanso mavitamini omwe ali ndi vitamini E ali mbali imodzi kapena yaikulu-tocopherol, izi ziyenera kupewedwa pokhapokha ngati zidalembedwa ndi wanu oncologist.
Kuthamangitsani
Matenda a khansa opatsirana a ROS1 amayamba kukhala achiwawa komanso kukula ndi kufalikira mofulumira, komanso amayankha njira yodalirika yochiritsira. Popeza mankhwala adangobvomerezedwa posachedwapa, n'zovuta kudziŵa momwe moyo wa munthu udzakhalira. Koma, mayankho omwe adawoneka pakalipano akulimbikitsa.
Mufukufuku wina nthawi yomwe Xalkori ankagwira ntchito (nthawi yomwe idasiya kugwira ntchito kwa theka la anthu koma akupitiriza kugwira ntchito kwa theka lina) inali miyezi 17; Ambiri amachitira mankhwalawa.
Akuyembekeza kuti anthu akadzagonjetsedwa ndi mankhwalawa omwe ena adzakhalapo, ovomerezeka, kapena m'mayesero a kachipatala omwe angasinthe mankhwala omwe asiya kugwira ntchito. Monga taonera, pali zizindikiro kuti izi zikhoza kukhala choncho.
Posachedwapa, kansalu yamapapo ndi kusintha ndi kusintha kumeneku kudzachiritsidwa ngati matenda aakulu, monga momwe timachitira matenda a shuga. Ngakhale khansayo isanachiritsidwe, mwachidziwikire tidzakhala odziteteza.
Thandizo ndi Community
Gulu labwino la anthu okhala ndi khansa ya m'mapapo ya ROS1 yasonkhana pamodzi. A ROS1Ders agwirizana kuti apititse patsogolo kufufuza kwa mankhwala a ROS1 abwino. Popeza izi ndi zachilendo zochepa kwambiri za thupi, ofufuza ambiri a m'midzi sakudziwa bwino kafukufuku wamakono komanso mayesero am'zipatala omwe alipo. Pa malo awo ali ndi mauthenga kwa madokotala komanso ochita kafukufuku omwe amafufuza khansa yabwino ya ROS1 ngati dokotala akufuna kufunsa wina mu mtima mwafukufukuwo. Global ROS1 Initiative ndi mgwirizano womwe ukugwirizanitsa ochita kafukufuku, odwala, osamalira odwala, ndi madokotala padziko lonse kuti akweze zotsatira za odwala ndikufulumizitsa kufufuza.
Mawu Ochokera
Palibe amene ayenera kudutsa khansa ya m'mapapo yekha. Ngati wokondedwa wanu atapezeka kuti ali ndi kansa ya m'mapapo, yang'anani maganizo awa pamene wokondedwa wanu ali ndi khansara yamapapo .
Kukhala nawo m'dera la khansa yamapapu kungakhale kothandiza kwambiri, ngakhale kwa iwo amene amapewa magulu ambiri. Popeza kansa yamapapu yabwino ya ROS1 ndi yachilendo, sizikuwoneka kuti mudzapeza anthu ambiri mumudzi mwanu amene akukumana ndi mavuto omwe mumakhala nawo.
Mu 2015, ku Lungevity HOPE Msonkhano, gulu lomwe limapangidwa ndi anthu okhawo omwe akuyang'aniridwa ndi kansa ya m'mapapo ya ROS1 yabwino. Iyi ndi nthawi yosangalatsa kwa anthu omwe ali ndi khansara yamapapo, monga odwala akugwirira ntchito limodzi ndi madokotala osati kumvetsa kokha matenda awo, koma kupereka zowonjezera pafukufuku omwe akufunikanso kuchitidwa.
Zotsatira:
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Drilon, A., Wamwamuna, R., Wagner, J. et al. Buku la crizotinib lopanda kusungunuka kwasintha kwa cabozantinib mankhwala kwa wodwala ndi khansa ya m'mapapo yokonzanso ya ROS1. Kafukufuku wa khansa yachipatala . 2015 Dec 16.
Katayama, R., Kobayashi, Y., Friboulet, L. ndi a. Cabozantinib ikugonjetsa crizotinib kukana mu kansa ya ROS1 yofiira-chonchi. Kafukufuku wa khansa yachipatala . 2015. 21 (1): 166-74.
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> Uchihara, Y., Kidokoro, T., Tago, K. et al. Mbali Yaikulu ya Vitamini E, a-Tocopherol Imaletsa Kuletsa Kuletsa Ntchito ya Crizoinib Kupyolera Maselo Osandulika ndi EML4-ALK. European Journal of Pharmacology . 2018 Feb 11. (Epub patsogolo pa kusindikiza).