March 2022: Mitsipa yeropa inofanirwa kuita semiti, ichidurura okisijeni mumatishu kuitira kuti ibudirire uye maseru edziviriro kuchenesa hutachiona kunze. Sango, kune rumwe rutivi, rinogona kuparara mumamota. Midziyo inokura nekukurumidza uye inoputika uye inomonyoroka pamakona akapinza, zvichiita kuti zviome kusiyanisa pakati petsinga netsinga. Inotanga kuita kunge midzi yemidzi ine gnarled kwete sango. Mumwe chiremba akairondedzera se“labyrinth ine bongozozo.”
Chaos isimba regomarara. Iro midzi yemidzi yakakombama inodzivirira mapundu akasimba kubva kumaseru anodzivirira muviri uye yakanganisa kuedza kukuru kwemasayendisiti ezvinodhaka mumakore achangopfuura kugadzira mishonga inosimudzira immune system nekuitungamirira kumamota.
Vatsvakurudzi vepaYunivhesiti yePennsylvania, kune rumwe rutivi, vanodavira kuti vangangove vakawana mushonga, nzira yokugadzirisazve tsinga dzeropa. Vanamazvikokota vanotenda kuti kana ikashanda, inogona kuvhura nzira yekurapa kweCAR-T inonangana nemamota akasimba, pamwe nekuvandudza kushanda kwemaitiro echinyakare senge radiation uye chemotherapy.
"Iri zano rakanaka uye rinogona kunge rakakosha," akadaro Patrick Wen, Dana-Farber neuro-oncologist anga asina kubatikana muchidzidzo ichi. “Vakaita basa rakanaka. Iyi inzira itsva yekusimudzira immunotherapy."
Avastin, anti-VEGF antibody yakave blockbuster, yakaramba ichitadza kuwedzera kupona mumhando dzakasiyana dzegomarara.
Vesainzi vaizofanira kunyatsoongorora nyaya yacho. Fan akaratidza kuti maitiro anozivikanwa se "endothelial cell transformation" chikamu chedambudziko mune zvinyorwa zviviri zvakaburitswa muna 2018. Maseru anotenderera tsinga dzeropa dzakatenderedza bundu dzinoita hunhu hwakaita sesero, zvichiita kuti dziwande uye dziwedzere panguva imwe chete. chiyero se stem masero.
Fan akaudza Endpoints, "Kune genetic reprogramming." "Vachawedzera kuita zvehasha."
Kurongazve ikoko kwakaitika sei, kunyange zvakadaro? Fan akafunga kuti kana aigona kupinza nzira, aigona kubva agadzira nzira yekuivhara. Akatanga nekugogodza kunze kinases, ari ma cellular motors anogona kukurudzira epigenetic alteration, kana "reprogramming," mumasero endothelial akaparadzaniswa nevarwere vane glioblastoma, rudzi rwegomarara rehuropi. Kunze kwe518, makumi matatu neshanu akanzvenga metamorphosis, nePAK35 ichiita zvakanaka.
Vatsvakurudzi vakatevera kuisa mapundu mumakonzo, mamwe aive nePAK4 uye mamwe aive nekinase yakabviswa: 80% yemakonzo asina kukwana PAK4 akararama kwemazuva makumi matanhatu, nepo mbeva dzese dzesango dzakafa mushure memazuva makumi mana. Masero eT akapinda nemamota zviri nyore muPAK60-inoshaya mbeva, maererano nekudzidza kwaFan.
Yakanga iri rombo rakanaka kuwanikwa: makore gumi apfuura, apo kinase inhibitors yaive hasha, makambani ezvinodhaka akange agadzira akawanda PAK inhibitors. Vazhinji vaive vasiiwa, asi Karyopharm aive achangopinda Phase I aine PAK4 inhibitor.
Kuti aone kana vagadziri vezvinodhaka vachigona kutora mukana wekuwanikwa uku, Fan nevamwe vake vakashandisa T masero kubva kumakonzo uye vakagadzira CAR-T. kurapwa kurwisa cancers.
Mishonga mitatu yakasiyana yakapiwa kumakonzo. Nekuda kwekuti kurapwa kweCAR-T hakuna kukwanisa kusvika bundu iri kuburikidza netsinga, harina kukwanisa kudzikisa bundu riri roga. Pachezvayo, mushonga weKaryopharm hauna mhedzisiro. Nekudaro, mushure memazuva mashanu, vakakwanisa kuderedza kukura kwebundu ne80%. Zvakawanikwa zvakaburitswa muNature Cancer svondo rino.
Fan akati, "Mugumisiro wakavhura maziso." "Ndinotenda kuti tiri kupupurira chimwe chinhu chinoshamisa."
Ehe, izvi zviri mumakonzo chete, asi Fan akatowana humbowo hwakakura hwekutora chikamu kwePAK4 mugomarara. Fan achiri kushanda pakuedza kwake, bhuku rakabva kuchikwata cheAntoni Ribas 'UCLA rakabudiswa muNature Cancer muna Zvita, zvichiratidza kuti PAK4 inhibitors inogona kubatsira T masero kupinda mukati memamota akasimba akasiyana. Vakaratidza mumakonzo kuti imwechete Karyopharm inhibitor inogona kuwedzera mhedzisiro yePD-1 inhibitors, ichibvumira masero eT akaiswa kuti asvike kumamota zvakanyanya.
