Kuongorora Biomarkers Iyo Inogona Kufanotaura Maitiro eKenza yako kuchinja
Pfungwa yekushandisa muviri wemunhu maitiro ekurwisana nekenza haisi inozi, asi kuwana iyi pfungwa yekushandura mukurapa kwave kuve kukwira kukwira.
Nhau dzakanaka ndeyokuti kuburikidza nekubudirira kwezvinoitika kwezvinodhaka zvinonzi immune checkpoint inhibitors , kushandiswa kwema immunotherapy kurapa kenza kwakavandudzwa. Iye zvino, kuwedzera pakuvandudza zvirwere zvekudzivirira zvirwere zvezvirwere inhibitor, vatsvakurudzi vari kutsvaga nzira dzekuziva zviri nani kutsvaga zvakanakisisa kune mishonga yakadaro.
Mune mamwe mazwi, nyanzvi dzinoda kubatanidza pamwe nevarwere vangangobatsirwe nehutachiwana hwechirwere ichi, zvinoreva kuti kanzvadzi yavo inogona kunge yakanganisa kana kuti inopera semugumisiro wekurapa uku.
Mhinduro dzacho hadzisi yakarurama, saka zvakakosha kutora nguva kuti unzwisise zvidzidzo zvekutsvakurudza kunoitwa mberi.
Mhinduro kune Immune Checkpoint Blockade: Biomarkers
Vatsvakurudzi vari kutsvaga nzira dzekuziva kuti ma immunotherapies achabatsira sei kune mumwe murwere. Zvakanaka, an oncologist (chiremba anoziva mukurapa kenza) anoda kuedza masero ekenza yemunhu kune biomarker (kana akawanda biomarkers).
Vaya vanoita zvinhu vanofanotaurira kuti munhu angaita sei kuti apindure kune rimwe remunotherapy. Nenzira iyi, nguva uye zvingave nemigumisiro yakaipa hazviparadzwi pamushonga unenge watozivikanwa kuti hauna kubudirira kune rudzi urwo rwekenza cell.
Mienzaniso mitatu yekenza zvinokonzera kenza zvinogona kubatsira kufanotaura kupindura kwemunhu kumusana chekuongorora inhibitor kunosanganisira:
- PD-L1 kutaura (ingava masero mukati memarara anoratidza protein inonzi yakagadzirirwa rufu-ligand 1)
- Mutenderedzwa mutoro (ingava masero mukati memumarara anotakura mhando dzakakura dzemagadzirirwo emuviri)
- Mismatch kugadzirisa nzvimbo (ingava masero mukati memarara inenge isina kugadziriswa kugadzika kusakosha kana kukwanisa)
Ngationgororei zvinhu zvitatu izvi zvakanyatsotsanangura.
Nenzira iyi unogona kunzwisisa zvishoma nesayenzi inokonzerwa nei maitiro ezvirwere zvekuchengetedzwa kwemasikirwo evhavha inhibitor angashanda kune mumwe munhu kwete mumwe.
PD-L1 Tsanangudzo
PDL-1 ipuroteni inoratidzwa pamusoro pemamwe masero emukenza. Chinangwa chayo ndechokunyengedzera masimba ezvirwere mumuviri kuti afunge kuti ma kenza masvikiro ane utano kana "akanaka." Nenzira iyo chiremera chinodzivirira maitiro ezvirwere zvekuzvidzivirira-sneaky, asi yakagadziriswa uye evasive mazano.
Zvisinei, pane mishonga ino inodzivisa PD-L1 . Nenzira iyo kenza inowanikwa nemusununguko wemuviri nokuti makero emukenza akarasikirwa masikisi avo, sekutaura. Zvinodhaka zvinodzivirira PD-L1 zvinonzi maune immune system checkpoint inhibitors uye zvinosanganisira:
- Tecentriq (atezolizumab): inodzivirira PD-L1
- Bavencio (avelumab): mabheji PD-L1
- Imfinzi (durvalumab): mabheji PD-L1
Iyi mishonga yakabatsira mukurapa kenza yakasiyana-siyana yakadai sekenza yemukaka, kwete-duku kemukirini yemapapu yemapapu, uye mutachiona wechirwere cheMerkel.
Iko kunewo immune checkpoint inhibitors inodzivirira PD-1 (iyo inosungira PD-L1 uye inogonawo kuratidzwa nekenza masero), uye izvi zvinosanganisira:
- Opdivo (nivolumab): zvinodzivirira PD-1
- Keytruda (pembrolizumab): mabheji PD-1
Kutsvakurudza kunoratidza kuti mishonga iyi inobatsira pakuchengetedza kenza yakadai semaranoma, isiri duku duku rekenza yemapapu, kenza yemutsvo, kenza yemukaka, kenza yemutsipa nehuro , uye Hodgkin lymphoma.
Mukutsvaga zvigadzirwa zvemhuka zvinogona kugadzirisa mukana wekuti munhu apindure kune rimwe remishonga iri pamusoro apa, vatsvakurudzi vatanga kuongorora masero ekenza yeP-PD. Zvechokwadi, apo kutsvakurudza kunoratidza PD-L1 kusanangurwa ndiyo imwe chinhu chinonyatsobatanidzwa nekupindura kune PD-L1 kana PD-1 blocker, zvimwe tsvakurudzo zvichiri kudiwa kuitwa.
Mune mamwe mazwi, PD-L1 mutauro wega wega ungasava chiratidzo chinokwanisika chekuti kenza yemunhu inopera kana kuparara nemumwe wemishonga inotaurwa pamusoro apa. Haisi chimiro chakakwana, asi yakanaka kune ikozvino.
Mutational Load
Kunze kwePP-L1 kutaura pamusoro pekenza masero, vatsvakurudzi vakaongorora kubatana pakati pemutoro wekutengesa kwemuviri uye kupindura kwaro kumusana wechirwere chekuzvidzivirira mu inhibitor.
Kutanga, kuitira kuti unzwisise kuti mutoro unorevei, unofanirwa kunzwisisa kuti kuchinja chii uye kuti izvi zvinorevei nekenza.
Chii Chinochinja?
Kushandurudza kunoshanduka muDNA zvakarongeka zvinoumba geni. Kuchinja-chinja kunogona kuva nhaka (kureva kuti yakapfuudzwa kubva kuvabereki vako) kana kuwanikwa.
Nekuchinja kwemuviri, kuchinja kwechiripo kunongowanikwa mumasero e-somatic (ose masero ari mumuviri, asi mazai nemasero emadhipa), saka haagoni kuendeswa kuchizvarwa chinotevera. Kuchinja kwemaitiro kunogona kuitika kubva kune zvakasikwa, sezvinoita zuva kukuvadza kana kusvuta, kana kubva pane zvakakanganisa apo DNA yesero iri kuzvienzanisa (inonzi kudzokorora).
Sezvakaita mumasero akareruka, kuchinja kunowanikwawo kune maitiro ekenza, uye mamwe marudzi ekenza ane huwandu hwekuchinja kune humwe. Semuenzaniso, mapepa maviri emukenza ane nhamba yakawanda yekutengesa kwemaitiro inomukenza wemapapu , kubva pakusvibira kune utsi hwefodya, uye melanoma , kubva pakuona zuva.
Chii Chinonzi Mutoro Mukuru?
Ikoko kune tsvakurudzo inoratidza kuti matumire ane huwandu hwakawanda hwemuteereri mutations (yakakwirira mutational load) inowanzoita kuti apinde mumuviri wechirwere chekudzivirira zvirwere mumuviri inhibitor kupfuura matumire ane maitiro akaderera ekutengesa genetic.
Izvi zvinonzwisisika nokuti, nekuwedzera kwekuchinja, chiremera chingangodaro chichinyanya kuzivikanwa nemusikirwo wemunhu. Mune mamwe mazwi, zvakaoma kuvanza nezvose izvo zviyero zvinoratidzika kusagadzikana.
Ichokwadi, izvi zvitsva zvinogadzirisa zvirwere zvinopedzisira zvichigadzira mapuroteni matsva-chaiwo anonzi neoantigens. Ndiwo maNeoantigens ayo anotarisirwa nehutachiona uye anorwiswa (anonzi kanonzi immunogenic neoantigens nokuti anokonzera mhinduro dzekuzvidzivirira mumuviri).
Mismatch Repair Status
Muviri womunhu unoenda kuburikidza nekugadziriswa kwegadziriro yekugadzirisa zvikanganiso zveDNA zvakaitwa panguva yekudzoka kwesero. Iyi nzira yekugadzirisa zvikanganiso zveDNA inonzi kusagadziriswa kugadziriswa.
Kutsvakurudza ku immune checkpoint inhibitors kwakaratidza kuti chirwere chisina kunaka-kugadzirisa chinogona kushandiswa kufanotaura kupindura kwomunhu kune immunotherapy. Kunyanya, zvipembenene zvisingagadziriswi kugadzirisa zvinoshaya (zvinoreva kuti zvose mapepa ekugadzirwa kwemajeri zvisina kunaka zvinoshandiswa kana kuti akanyarara) haagoni kugadzirisa DNA zvikanganiso.
Kana kenza masero ane kuderedzwa kukwanisa kugadzirisa DNA kukanganisa, vanogona kuunganidza zvinhu zvakawanda zvinoita kuti vaonekwe nemaitiro ezvirwere zvemuviri . Mune mamwe mazwi, vanotanga kutarisa zvakasiyana-siyana nemasero evhesi (asinganzwisisi).
Kutsvakurudza kunoratidza kuti kanzira ine kusakonzera-kugadzirisa kukanganisa kune masero akawanda emachena eropa ayo akasiya ropa kuti apinde mumaronda-chiratidzo chekudzivirira kwemasimba omumakumbo uye chinoratidza kuti kenza iyi inowanzoshungurudzika nejinga rekudzivirira immunotherapy.
Izvi zvinopesana nekusaziva-kugadzirisa hutano hwekenza, nekuratidza chiduku chechichena chemuviri chemuviri chinoputika.
Cancer uye Immune System: Kubatana Kwakakomba
Kubva kwema immunotherapies iyo inotarisa kuongorora mapuroteni yakaunza mufaro uye tariro kune avo vanobata uye vanopedza kenza. Asi kupa chimiro chisina kukwana cheP PD-L1 kutaura, mamwe mabhizimisi anovimbika anodikanwa kuonekwa uye kuongororwa. Kunyange zvazvo kushanduka kwemitambo uye DNA kugadzirisa zvinhu zvisina kunaka zvinotanga, zvidzidzo zvichiri kudiwa kuti zvishandiswe kuti zvishandiswe nevarwere.
Nezvo, kusarudza mukana wemunhu wekupindura kune rimwe remunotherapy inogona kubva kubva kuongororwa kwemhando dzakasiyana-siyana dze deta-chiremera che genetic profile, sekutaura.
Shoko Rinobva
Pachirevo chekupedzisira, zvakakosha kuti urege kuvharwa zvakare nemashoko akaoma akaiswa pano.
Pane kudaro, chinyatsoziva kuti kunyange uchivimbisa uye unofadza kwazvo, zvirwere zvekudzivirira zvirwere zvekudzivirira zvirwere zvinokonzerwa neA FDA chete zvinogamuchirwa kutarisa mhando dzakasiyana uye zvikamu zvekenza. Zvinogona kana kuti hazvingavi mhinduro kune iwe kana mudiwa asi kuratidza kufambira mberi kwakanyanya mukugadzirwa kwemishonga itsva yekenza. Chero nzira, ramba uine tariro uye ramba uchifamba rwendo rwako rwakasimba.
> Sources:
> Farkona S, Diamandis EP, Zimbabwe IM. Cancer immunotherapy: kutanga kwekuguma kwekenza? BMC Med . 2016 May 5; 14: 73.
> Le Dt et al. PD-1 kudzivirirwa mumakumbo nechisingaiti-kugadzirisa kukwana. N Eng J Med . 2015 Jun 25; 372 (26): 2509-20.
> Masucci GV et al. Kuzadzikiswa kwezvinhu zvinokonzera maitiro kufanotaura kupindurwa kwekudzivirira immunotherapy mukenza: Bhuku 1 - pre-analytical uye analytical validation. J Mukadzi Kanzera . 2016 Nov 15; 4: 76. eCollection 2016.
> Mouw KW, Goldberg MS, Konstantinopoulos PA, D'Andrea AD. DNA inokuvadza uye kugadzirisa zviratidzo zvekudzivirira zvirwere. Cancer Discov . 2017 Jul; 7 (7): 675-93.
> Shoushtari AN, Wolchok J, Hellman M. (2017). Nheyo dzekenza immunotherapy. Atkins MB, ed. Kusvika pari zvino. Waltham, MA: UpToDate Inc.