March 2022: Imithambo yegazi kufanele iziphathe njengezihlahla, ithululela umoya-mpilo ezicutshini ukuze ichume namaseli omzimba ukuze ahlanze izifo. Ngakolunye uhlangothi, ihlathi lingahamba kabi ngenxa yamathumba. Imikhumbi ikhula ngokushesha futhi iqhume futhi isonteke ema-engeli abukhali, okwenza kube nzima ukuhlukanisa phakathi kwemithambo nemithambo. Iqala ukufana nephansi lempande eshwabene kunehlathi. Omunye udokotela wayichaza ngokuthi “i-labyrinth ephithizelayo.”
Isiphithiphithi siwuphawu lomdlavuza. Leso sisekelo sezimpande ezigobile sivikela amathumba aqinile kumangqamuzana omzimba futhi sibhuntshise imizamo emikhulu yososayensi bezidakamizwa eminyakeni yamuva nje yokuklama imithi ezoshukumisa amasosha omzimba futhi iwaqondise emathunjini.
Ngakolunye uhlangothi, abacwaningi baseYunivesithi yasePennsylvania bakholelwa ukuthi bathole ikhambi, indlela yokulungisa kabusha imithambo yegazi. Ochwepheshe bakholelwa ukuthi uma isebenza, ingavula indlela yokwelashwa kwe-CAR-T eqondise izimila eziqinile, kanye nokuthuthukisa ukusebenza kahle kwamasu esintu amaningi njengemisebe ne-chemotherapy.
"Kuyisu elihle futhi elibalulekile," kusho uPatrick Wen, udokotela we-neuro-oncologist wase-Dana-Farber owayengahileleki ocwaningweni. “Benze umsebenzi oncomekayo. Lena indlela entsha yokuthuthukisa i-immunotherapy."
I-Avastin, i-anti-VEGF antibody eyaba i-blockbuster, ihlulekile njalo ukwandisa ukusinda ezinhlobonhlobo zomdlavuza.
Ososayensi kuzodingeka bajule kule ndaba. Umlandeli ubonise ukuthi inqubo eyaziwa ngokuthi "i-endothelial cell transformation" iyingxenye yenkinga ezincwadini ezimbili ezishicilelwe ngo-2018. Amangqamuzana ahlanganisa imithambo yegazi ezungeze isimila ahlakulela izimfanelo ezifana ne-stem cell, ewavumela ukuba ande futhi ande ngesikhathi esifanayo. izinga njengama-stem cells.
Umlandeli utshele i-Endpoints, “Kukhona ukuhlelwa kabusha kofuzo.” “Bazoba nolaka kakhulu.”
Nokho, lokho kuhlelwa kabusha kwenzeka kanjani? Umlandeli ucabange ukuthi uma engakwazi ukuvala indlela, angakwazi ukwenza iqhinga lokuyivimba. Uqale ngokukhipha ama-kinases, okungamamotho amaselula angakhuthaza ukuguqulwa kwe-epigenetic, noma “ukuhlelwa kabusha,” kumaseli e-endothelial ahlukaniswe neziguli ezine-glioblastoma, uhlobo lomdlavuza wobuchopho olunolaka. Kwabangu-518, abangama-35 bagweme ukuguquguquka, i-PAK4 yenza kahle kakhulu.
Abacwaningi ngokulandelayo bafaka izimila kumagundane, amanye awo ayene-PAK4 kanti amanye ayekhiphe i-kinase ngokofuzo: I-80% yamagundane antula i-PAK4 aphila izinsuku ezingu-60, kuyilapho wonke amagundane ohlobo lwasendle afa ngemva kwezinsuku ezingu-40. Ama-T cell ahlasele amathumba kalula kakhulu kumagundane ashoda nge-PAK4, ngokocwaningo lwabalandeli.
Kwaba ukutholakala kwenhlanhla: eminyakeni eyishumi edlule, lapho ama-kinase inhibitors ayethukuthele, izinkampani zezidakamizwa zazenze ama-PAK inhibitor amaningi. Abaningi babeshiywe, kodwa uKaryopharm wayesanda kungena esigabeni sokuqala nge-PAK4 inhibitor.
Ukuze banqume ukuthi abathuthukisi bezidakamizwa bangakwazi yini ukusizakala ngalokhu kutholwa, u-Fan nozakwabo basebenzisa ama-T cell avela kumagundane futhi benza i-CAR-T. ukwelashwa ukuhlasela umdlavuza.
Amagundane anikezwa izinqubo ezintathu ezahlukene. Ngenxa yokuthi ukwelapha kwe-CAR-T akukwazanga ukufinyelela isimila ngemithambo, ayikwazanga ukushwabana usayizi wesimila ngokwawo. Ngokwayo, umuthi weKaryopharm wawungenawo umphumela. Kodwa-ke, ngemva kwezinsuku ezinhlanu, bakwazi ukuncipha usayizi wesimila ngo-80%. Okutholakele kushicilelwe ku-Nature Cancer kuleli sonto.
Umlandeli uphawule wathi, “Umphumela ovula amehlo ngempela.” "Ngikholwa ukuthi sibona into engavamile."
Vele, lokhu kumagundane kuphela, kodwa i-Fan isivele ithole ubufakazi obuningi bokubamba iqhaza kwe-PAK4 kumdlavuza. Ngenkathi u-Fan esasebenza esivivinyweni sakhe, incwadi evela ethimbeni lika-Antoni Ribas le-UCLA yanyatheliswa kuyi-Nature Cancer ngoDisemba, okubonisa ukuthi ama-PAK4 inhibitors angasiza ama-T cell ukuthi angene azungeze izimila eziqinile ezihlukahlukene. Babonise kumagundane ukuthi i-Karyopharm inhibitor efanayo ingase ithuthukise imiphumela ye-PD-1 inhibitors, ivumele amaseli e-T acushiwe ukuthi afinyelele izimila ngempumelelo kakhudlwana.
