EML4-ALK mu khansa ya m'mimba komanso udindo wa crizotinib
Ngati dokotala wakuuzani kuti muli ndi kanthani ya ALK kapena khansa yamapapo ya ALK, mungamve ngati muli m'dziko limene limalankhula chinenero china popanda womasulira. Kodi ALK ndi yani, ndiyotani kukonzanso kachilombo ka ALK, nanga anthu omwe ali ndi khansa ya m'mapapo ya ALK amachiritsidwa bwanji?
Tanthauzo la kusintha kwa ALK
Kukonzekera kwa ALK ndi chinthu chosadziwika mu jini lomwe lingathe kuchitika m'maselo a khansa monga maselo a kansa yamapapo.
Monga ndemanga yofulumira, majini ndi mbali ya ma chromosomes mu DNA yathu yomwe imatengera zinthu monga mtundu wathu wa diso ndi mtundu wa tsitsi. Iyenso ndi ndondomeko yomwe imateteza mapuloteni omwe amayendetsa matupi athu mofulumira-kapena amachititsa maselo kugawa ndi kukula.
Maselo a khansa ndi maselo amene asintha kwambiri miyandamiyanda ya zamoyo-kusintha kwa majini-pokhala maselo a khansa. Monga anthu, khansara iliyonse ndi yosiyana ndipo imasintha kusintha kosiyana ndi kusintha kwa majini. Mitundu imeneyi imasinthidwa ndi mapuloteni omwe sali achilendo ndipo amachita ntchito zosalongosoka, monga kuyendetsa kukula kwa khansa.
Zowoneka mu 2007, kusintha kwa ALK ndi kusintha kwa geni lotchedwa ALK (aplastic lymphoma kinase.) Kuti zikhale zolondola, kusintha kumeneku ndiko kwenikweni kuyambitsa upangidwe wa jini-kusakaniza kwa majini awiri otchedwa ALK ndi EML4 (echinoderm microtubule-linked protein monga 4.) Jini yosawonongeka (genetic fusion) ndi zizindikiro za mapuloteni osadziwika otchedwa tyrosine kinase (pali mitundu yambiri ya tyrosine kinases.)
Tyrosine kinases ndi mapuloteni (mapuloteni) omwe amachititsa ngati mankhwala amtundu, kutumiza zizindikiro ku maselo okulirapo omwe amachititsa kuti selo ligawike ndikuchulukitsa. Mwachidule, tyrosine kinase "imayendetsa" kapena imapangitsa kukula kwa khansara (kusintha monga EML4-ALK fusion gene amadziwika kuti "kusintha kwasinthiti.")
Gawo losangalatsa la zomwe apeza ndikuti tsopano ma khansa amatha kuchiritsidwa ndi tyrosine kinase inhibitors, mankhwala omwe amaletsa tyrosine kinase (pakadali pano mapuloteni a fusion EML4-ALK) ndipo amaletsa kukula kwa khansa potseka zizindikiro zomwe zimanena mu selo kugawa. Mwachidziwitso kulamulira kansalu ya "kuchoka" kusinthana, mankhwalawa apanga miyoyo ya anthu ena omwe ali ndi khansa omwe ali ndi kusintha kwa ALK.
Anthu ena amadziwika ndi kusintha kwina komwe kumawoneka mwa anthu ena omwe ali ndi khansa ya m'mapapo yopanda maselo, yotchedwa kusintha kwa EGFR . Kusintha kumeneku kumathandizanso kupanga mapuloteni achilendo a tyrosine kinase, ndipo EGFR tyrosine kinase inhibitor Tarceva (erlotinib) yowonjezera moyo wa anthu ambiri omwe ali ndi khansa ya m'mapapo omwe ali ndi chotupa chabwino cha kusinthaku.
Nkhani zotsatirazi zikufotokozanso za kusintha kwa kusintha kwa maselo a khansa:
Kodi Khansara ya Lung Posakaniza N'chiyani?
Khansa yabwino ya khansa ya m'mapapo imatanthawuza anthu omwe ali ndi khansa yamapapu yomwe imayesa kusintha kwa kusintha kwa ALK (mazira a EML4-ALK fusion.) Kusintha kumeneku kulipo pakati pa atatu ndi asanu pa anthu 100 alionse omwe ali ndi khansa ya m'mapapo yopanda maselo . Izi zingamveke ngati chiwerengero chochepa poyang'ana, koma pakuwona chiwerengero chachikulu cha anthu omwe ali ndi khansara yamapapaka chaka chilichonse ku US (akuyesedwa kukhala oposa 200,000 mu 2017), nambala imeneyo ndi yaikulu kwambiri.
Kodi ALK Rearrangements Yangowonedwa Pokhapokha mu Khansara Yam'mimba?
Mankhwalawa a EML4-ALK amadziwika ndi anthu ena omwe ali ndi neuroblastoma ndi aplastic lalikulu cell lymphoma .
Kufotokozera Kusintha kwa Anthu Ndi Khansa
Mfundo yosokoneza ndi yofunika kukumbukira ndi yakuti mchitidwe wa fusion wa EML4-ALK sikutengera mwachisawawa monga BRCA1 ndi BRCA2 kusintha kwa anthu ena ndi khansa ya m'mawere (ndi khansa zina). Anthu omwe ali ndi kansa ya m'mapapo ya EML4 -KUKHALITSIDWA kwa mitundu yosiyanasiyana ya mafupa sikunabadwe ndi maselo omwe anali ndi kusintha kumeneku ndipo sanakhale ndi chizoloŵezi chokhala ndi kusintha kumeneku kuchokera kwa makolo awo. Mmalo mwake, ichi ndi kusintha komwe kumawoneka komwe kumawoneka m'maselo ena a khansa monga gawo la chitukuko cha khansa.
Kudziwa
Kusintha kwa ALK kumatengedwa ndi kufotokoza maselo a zitsanzo za chotupacho. Ndikofunika pakuyesera izi kuti minofu yokwanira ya opaleshoni ya khansa ya m'mapapo kapena ya mapapu imapezeka. Ochita kafukufuku akuyang'aniranso njira zodziwira ngati kusintha kwa ALK kulipo musanayese kuyesa kwa majeremusi, kapena kungalowe m'malo mwa kuyesedwa kwa majini. Zinthu zochepa zomwe zimasonyeza kuti kusintha kwa ALK kungakhalepo monga:
- Ntchito yamagazi - Chitsanzo chotchedwa CEA (carcinoembryonic antigen) chimakhala choipa pakati pa anthu okhala ndi kusintha kwa ALK.
- Kafukufuku wina - Phunziro limodzi, zotupa zabwino za ALK zinkawoneka zolimba ndipo zinalibe kanthu kena kamene kamatchedwa galasi maonekedwe. Mosiyana ndi zimenezo, 50 peresenti ya anthu omwe sanasinthidwe ndi ma radiology amaphunzira ndi galasi yamaonekedwe.
Komabe, panthawiyi, kufotokoza maselo (maselo a majini) kumakhalabe chiyeso chabwino kwambiri ndipo ndilo dongosolo la chisamaliro.
Ndani Angakhale Kuti Ali ndi Mutundu wa ALK?
Mitundu ya kusintha kwa thupi yomwe ilipo m'magazi amapapu amasiyana malinga ndi mtundu wa khansa yamapapo . Matenda a EML4-ALK amadziwika kwambiri mwa anthu omwe ali ndi khansa yaing'ono ya m'mapapo ya mapapo yotchedwa lung adenocarcinoma . Izi zinkati, kawirikawiri, ALK yapezeka mwa anthu omwe ali ndi squamous cell carcinoma m'mapapo (mtundu wina wa khansa yaing'ono ya mapapu ya m'mapapo) ndi khansa yaing'ono yamapapo ya m'mapapo .
Palinso anthu ena omwe ali ndi kachilombo ka fusion. Izi zikuphatikizapo odwala, anthu omwe sanasute (kapena kusuta pang'ono), akazi, ndi omwe ali ndi mtundu wa East Asia . Mu kafukufuku waposachedwapa, anapeza kuti odwala osachepera zaka 40 anayesedwa zabwino kuti EML4-ALK fusion gene ikhale pafupifupi 50 peresenti ya nthawi (mosiyana ndi 3 mpaka 5 peresenti ya anthu a zaka zonse ndi khansara yamapapo.)
Ndani ayenera kuyesedwa kuti asinthidwe ndi ALK Mutation (Rearrangement)?
Mabungwe angapo adagwirira ntchito pamodzi kuti apange malangizo omwe ayenera kuyesedwa kuti asinthidwe ndi ALK. Chigwirizano chinali chakuti odwala onse omwe ali ndi masewera apamwamba adenocarcinoma ayenera kuyesedwa kwa kusintha kwa ALK ndi EGFR kusintha, mosasamala za chikhalidwe cha amuna, chikhalidwe cha kusuta fodya, zifukwa zina zoopsa, ndi mtundu.
Njira imodzi ndi yakuti matenda ena ali ndi malo omwe amaoneka ngati mitundu yosiyana ya khansa ya m'mapapo. Mwachitsanzo, minofu mbali imodzi ya chiwopsezo imawoneka ngati adenocarcinoma ndi minofu mu gawo lina la nyemba zowonongeka zingayang'ane ngati khansa yaing'ono ya m'mapapo.
Pali zina zomwe madokotala angapange pazinthu izi. Mwachitsanzo, kuyezetsa kukhoza kutonthozedwa kwa munthu yemwe sanasute konse, ngakhale kuti khansa ya mapapo ya mapapo sioneka ngati adenocarcinoma. Malangizowo angasinthe ngati zambiri zimaphunzira za kusintha kumeneku, ndipo zina zamasinthika zimapezeka ndi zotsatira zothandizidwa.
Kodi ALK Imayambitsa Kanseri Yabwino Kwambiri?
Ngakhale kuti zakonzedweratu za ALK mu kansa yamapapu zinangowonekera m'chaka cha 2007, mankhwala (tsopano omwe anayi) kwa anthu omwe ali ndi chisinthiko ichi (komanso ali ndi khansara ya m'mapapo) amavomereza kale ndi FDA. Chivomerezochi cha FDA - zaka 4 zokha kuchokera pamene chigwirizanitsochi chinayambanso - chiri chosangalatsa pakati pa mankhwala a khansa ya m'mapapo omwe sanawonjezeke kwambiri m'zaka makumi angapo zapitazo.
Tiyeni tiyambe mwa kukamba za mankhwala ovomerezeka oyamba, ndiyeno perekani mankhwala ena omwe tsopano avomerezedwa kwa omwe ali ndi rearrangements ALK
Zimagwira bwanji ntchito ? Mankhwala - Xalkori (crizotinib) ndi chiletso cha tyrosine kinase. Pachifukwa ichi, Xalkori imamangiriza kwa receptor ya tyrosine kinase pamwamba pa maselo a khansa yamapapo ndipo imaletsa mapuloteni a ALK osadziwika. Njira yosavuta kumvetsetsa ndi kuganizira za tyrosine kinase receptor monga lock, ndi protein tyrosine kinase (yopangidwa ndi jini losasintha) monga chinsinsi. Anthu omwe ali ndi kusintha kwa ALK ali ndi fungulo losazolowereka. Pamene fungulo "litayikidwa," zizindikiro zimatumizidwa ku malo okula kuti maselo agawanire popanda kuima. Mankhwala monga Xalkori ntchito mwa kutseka chinsinsi - ngati ngati mutadzaza chingwe chakumaso kwanu ndi konkire. Popeza fungulo (puloteni yosadziwika) silingathe kulowetsa (limbani ndi receptor,) chizindikiro cha selo kuti chigawanitse ndikukula sichitha kufika pamalo olamulira komanso kusamvana kwa maselo (kuchepa kwa chifuwa).
Zimagwira ntchito bwino bwanji? Kafukufuku apeza kuti mankhwala ndi Xalkori amatha kupulumuka kwapakati pa miyezi 7 mpaka 10. Pali pafupifupi 50 mpaka 60% ofunika kuyankha kwa mankhwala. Izi zingawoneke zosangalatsa, makamaka poyerekeza ndi chithandizo cha khansa zina, koma zodziwika kuti anthu omwe ali m'maphunzirowa adalandira kale ndipo analephera kale mankhwala am'mbuyomu ndipo chiwerengero choyankhidwa choyankhidwa kuti apitirize mankhwala a chemotherapy angakhale ozungulira 10% ndi avareji Kupulumuka kwapanda phindu kwa miyezi itatu.
Ngakhale kuti chiwerengero cha Xalkori chotsatira chili bwino kusiyana ndi mankhwala a chemotherapy, kafukufuku sanapeze kuti Xalkori amachititsa kuti moyo wonse ukhalepo . Komabe pamene kupulumuka kuli kofunikira, khalidwe la moyo ndilofunikanso. Kuletsa kuchepa kwa khansa kungachepetse zizindikiro zokhudzana ndi khansara, ndipo kwenikweni, odwala omwe ali ndi Xalkori anali ndi zizindikiro zochepa zokhudzana ndi kansa ya m'mapapo ( kupuma pang'ono , kupweteka pachifuwa, ndi kutopa.) Ndizosakayikitsa ngati phunziroli likuyesedwa molondola kupulumuka chifukwa anthu omwe ali mu phunziroli adapatsidwa "kuwoloka" ndikugwiritsa ntchito mankhwala ena ngati zizindikiro zawo zikupita patsogolo. Anthu ambiri amasiya chemotherapy ndi kusintha crimetinib kuposa njira ina.
Popeza Xalkori inavomerezedwa, mankhwala ena amavomerezedwa kuti azisamalira khansa ya m'mapapo ya ALK. Izi zikuphatikizapo:
- Zykadia (ceritinib)
- Alectinib (alencensa)
Kuwonjezera apo, mankhwala atsopano kuthana ndi khansa ya m'mapapo ya ALK, Alunbrig (brigatnib) inavomerezedwa pa April 28, 2017.
Pakalipano tikuganiza kuti alectinib imapereka moyo wautali wautali kuposa crizotinib (miyezi 25.7 ndi miyezi 10.4) ndipo ili ndi zotsatira zochepa. Izi zanenedwa, ndizofunikira kulankhula ndi a oncologist anu kuti mankhwala awa ndi otani omwe angakuthandizeni kwambiri.
Ndikofunika kukumbukira kuti tyrosine kinase inhibitors si mankhwala a kansa ya m'mapapo , koma m'malo mwake amalola kuti chotupa chikhale "chosungidwa" monga momwe mankhwala a shuga angayambitsire matenda koma sachiza. Tikuyembekeza kuti mtsogolomu, khansara yamapapo, pafupifupi mitundu ina ndi kusintha kwina, ingatengedwe ngati matenda ena odwala monga shuga.
Kutsutsana
Mwamwayi, ngakhale kuti theka la anthu amamvera bwino mankhwala, nthawi zambiri amayamba kutsutsa ndipo mankhwalawa amalephera. Kwa anthu amene amatha kutsutsa, palinso zosankha zomwe zilipo. Alectinib anapatsidwa mwayi wolemba mu 2013 kuti anthu omwe ali ndi khansa ya m'mapapo ya ALK-resistant crimetinib. Mu March wa 2014 mankhwala ena - Zykadia (ceritinib) - anapatsidwa chithandizo cha mankhwala a FDA. Miyeso yoyamba yomvetsera ku Zykadia inali yofanana ndi ya Xalkori. Kuonjezera apo - anthu ambiri omwe adatsutsa Xalkori adayankha Zykada. Mankhwala atsopano akuphunziridwa m'mayesero azachipatala kwa anthu omwe amatsutsa, ndipo ena ofufuza akuyembekeza kuti m'tsogolomu odwala angapangidwe mofanana ndi mankhwalawa ngati kukana kukukulirakulira.
Kuonjezera apo, zotupa nthawi zambiri zimasintha (kukhazikitsa kusintha kwatsopano) pakapita nthawi. Nthawi zina mankhwala omwe amamenyana ndi kusintha kwina kosamalidwa bwino (monga EGFR) angagwire ntchito ngakhale kuti chotupa sichinali chokoma kwa kusintha kwa EGFR. Tikuyembekeza kuti posachedwapa tidzatha kudwala kansa ya m'mapapo - makamaka gawoli - mofanana momwe timachitira ndi matenda ena akuluakulu.
Ndi mankhwala ati omwe ali abwino kwambiri?
Zilonda zamakono zikupitirizabe kuyesa kuphunzira zambiri za mankhwala anayi omwe alipo tsopano akugwira ntchito bwino kwambiri. Pali umboni wina wosonyeza kuti mankhwala atsopano (omwe ali ndi ALK rearrangements ndi kusintha kwasintha) akhoza kuthandizira bwino matendawa. Chifukwa cha kupezeka kwa magazi, ubongo wambiri womwe umalepheretsa poizoni ambiri (kuphatikizapo chemotherapy ndi mankhwala othandiza) kuti asalowe muubongo, mankhwala ambiri omwe timawapeza lero kuti athetse khansa ya m'mapapo sagwira bwino ubongo. metastases. Kwa omwe ali ndi masewases ochepa chabe a ubongo, stereotactic brain radiotherapy (SBRT) kapena mpeni wa cyber wapereka mwayi wosamalira izi, komabe m'tsogolomu, tidzakhala ndi mankhwala omwe angathe kuwongolera bwino.
Chenjezo Pa Vitamini E Zakudya
Nthawi zonse timachenjeza anthu kuti azitenga mankhwala ena opatsirana pogwiritsa ntchito khansa popanda kuyamba kuyankhula ndi a oncologist, ndipo izi ndi zofunika ndi crizotinib (ndipo mwina zina zothandizidwa ndi mankhwala). Mu 2018, anapeza kuti chigawo china cha vitamini E chotchedwa-tocopherol chingasokoneze kwambiri crizotinib mankhwala. Vitamini E (kapena mwina gawoli) onse anatsutsa ntchito ya crizotinib, komanso analetsa khungu la khansa imfa chifukwa cha crizotinib. Zinaoneka ngati zowona kwa-tocopherol, osati mbali ina ya vitamini E monga y-tocopherol. Izi zinati, mavitamini E ambiri ndi mavitamini ena omwe ali ndi vitamini E nthawi zambiri amakhala ndi-tocopherol monga chowongolera.
Zotsatira Zotsatira za Chithandizo
Monga ndi mankhwala ambiri a khansa, mankhwala monga Xalkori ali ndi zotsatira. Mwamwayi ambiri mwa awa ndi ovuta kwambiri kuposa momwe anthu amachitira panthawi ya mankhwala a chemotherapy. Zizindikiro zambiri zomwe anthu amamva pa Xalkori zimaphatikizapo mavuto owonetsa, kutsegula m'mimba, kunyowa, kupuma pang'ono, ndi kuyesa kwachilendo kosadziwika. Chosavuta koma chowopsa kwambiri chomwe chawonekera ndicho chitukuko cha matenda a m'mapapo omwe angathe kupha.
Tsogolo
Gulu la Fusion ya ALK ndi chimodzi mwa kusintha kwakukulu komwe kumachitika m'maselo a kansa yamapapo. Tikuyembekeza kuti ngati izi zikumvetsetsedwa bwino, mankhwala atsopano adzapezeka omwe sangangowononga kukana koma akuwongolera zina zolakwika (kusinthana kwasintha) mu maselo a khansa. Pankhani ya crizotinib, amaganiza kuti mankhwalawa angathandizenso anthu ena omwe alibe ALK fusion ya jini koma ali ndi majeremusi ena amtundu wa tyrosine kinase (monga ROS1 rearrangement .)
Ndemanga Zomaliza
Kuti mankhwala agwiritsidwe ntchito mofanana ndi ALK, anthu omwe ali ndi khansa ya m'mapapo ayenera kuyesedwa kuti asinthe. Ngakhale malangizo akuvomereza kuti ayese aliyense yemwe ali ndi adenocarcinoma ndipo ntchitoyi ikuwonjezeka, palinso anthu ambiri omwe sanagwiritsidwe ntchito.
Pali zifukwa zingapo izi. Imodzi ndi yakuti iyi ndi malo osintha mofulumira kwambiri a mankhwala, ndipo palibe dokotala yemwe angakhale pamwamba pa kupeza kwatsopano kulikonse. Funsani mafunso. Chitani kafukufuku pang'ono (kapena mukhale ndi mnzanu kapena wokondedwa wanu fufuzani chifuwa chanu.) Taganizirani kupeza lingaliro lachiwiri pa malo opatsirana khansa omwe amawona odwala ambiri a khansa ya m'mapapo.
- Mmene Mungasankhire Chithandizo cha Khansa Yam'mimba
- Njira Zoyamba Pamene Mukudziwika Kwatsopano ndi Khansa Yam'mimba
- Mmene Mungalimbikitsidwire ndi Khansa
Chodetsa nkhaŵa china ndizofunika. Mankhwala atsopano omwe amayambitsa zovuta za maselo a khansa nthawi zambiri amabwera ndi mtengo wotsika mtengo. Koma pali zosankha zomwe zilipo. Kwa iwo omwe alibe inshuwalansi, pali boma komanso mapulogalamu apadera omwe angathandize. Kwa iwo omwe ali ndi inshuwalansi, mapulogalamu othandizira a copay angathandize kuchepetsa ndalama. Nthawi zina, wopanga mankhwalawo akhoza kupereka mankhwala pamtengo wotsika. Ndipo chofunika kwambiri, ngati kutenga nawo mbali mu mayesero a zachipatala , mankhwala, komanso maulendo a maofesi, nthawi zambiri amaperekedwa kwaulere.
Monga ndemanga yomaliza, ziribe kanthu kuti mumaphunzira zochuluka bwanji kuchokera kwa gulu lanu lachipatala, palibe kanthu monga kumva kuchokera kwa anthu amene akhalapo komweko ndipo amalandira mankhwala omwe mungalandire. Fufuzani magulu othandizira anthu omwe ali ndi kansa ya m'mapapo ndikufunseni ngati wina ali ndi kusintha kwa ALK. Mabungwe ena monga LUNGevity ali ndi ntchito yowonjezera (LUNGevity LifeLine) momwe angakugwirizanitseni ndi wina yemwe ali ndi khansara yamapapo yemwe ali ndi mtundu wofanana ndi sitepe ya chotupacho.
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