KRAS Inhibitor Adagrasib Tau Ntawv Pov Thawj Ua Kev Kho Mob Los Ntawm FDA!

Niaj hnub no, Mirati Therapeutics tshaj tawm tias US FDA tau tso cai rau lub tuam txhab' KRAS G12C inhibitor adagrasib kev kho kho mob kev xaiv rau kev kho mob uas tsis kho mob qog noj ntshav qog noj ntshav (NSCLC) cov neeg mob KRAS G12C hloov pauv.

Ua ntej qhov no, Mirati thiab Zai Lab tau mus txog qhov kev koom tes thiab ntawv tso cai pom zoo ntawm kev txhim kho thiab kev lag luam ntawm cov khoom me me KRASG12C inhibitor adagrasib hauv Tuam Tshoj. Adagrasib yog kev tshawb fawb, xaiv tau zoo thiab muaj txiaj ntsig zoo hauv qhov ncauj me me molecules KRASG12C inhibitor, ua kom zoo los tswj kev tiv thaiv. Cov yam ntxwv no tseem ceeb heev rau kev kho mob qog noj ntshav KRASG12C uas rov tsim dua txhua 24-48 teev. Cov kev tshawb fawb ntawm adagrasib tau qhia tias cov tshuaj muaj lub neej ib nrab ntev, nthuav dav cov ntaub so ntswg, thiab tiv taus zoo. Nyob rau tib lub sijhawm, adagrasib tau qhia pom ib tus neeg sawv cev ua haujlwm tau zoo hauv cov qog nqaij hlav ntsws tsis-me, mob qog noj ntshav, mob qog noj ntshav thiab lwm yam qog nqaij hlav nrog KRASG12C hloov pauv.

Txiav txim los ntawm cov ntaub ntawv mob qog noj ntshav thoob ntiaj teb tshiab tshaj tawm los ntawm International Agency for Research on Cancer (IARC) ntawm Lub Koom Haum Saib Xyuas Kev Noj Qab Haus Huv Hauv Xyoo 2020, muaj 9.96 lab tus mob qog noj ntshav tuag thoob ntiaj teb hauv xyoo 2020, ntawm uas 1.8 lab yog mob ntsws cancer tuag, ntau tshaj lwm yam hom mob qog noj ntshav thiab qeb duas ntawm kev tuag mob qog noj ntshav. Zauv ib. Xyoo 2020, cov neeg tuag mob qog noj ntshav hauv Suav teb yog 3 lab, thiab mob ntsws ntsws tuag yog nyob deb ua ntej, mus txog 710,000, suav txog 23.8% ntawm tag nrho cov neeg tuag vim mob qog noj ntshav. Yuav ua li cas txhawm rau mob qog noj ntshav hauv lub ntsws yog ib qho ntawm ntau yam teeb meem uas cov kws kho mob hauv zej zog xav kom kov yeej.

Raws li kev tshawb fawb tam sim no, RAS kev hloov pauv noob yog ib yam ua rau mob qog noj ntshav loj. Kev hloov pauv KRAS feem ntau tshwm sim hauv mob qog noj ntshav, mob qog noj ntshav, thiab mob qog noj ntshav, yog li lawv tau dhau los ua lub hom phiaj nrov rau cov kws tshawb fawb kom kov yeej.

Xyoo tsis ntev los no, kev tsom mus rau RAS ncaj qha sawv cev los ntawm KRAS G12C inhibitors tau ua tiav qhov tseem ceeb. KRAS noob hloov pauv feem ntau yog tsom rau codons 12, 13 thiab 61, uas codon 12 kev hloov pauv ntau dua 80%, suav nrog G12A, G12C, G12D, G12R, G12S thiab G12V, thaum KRAS G12C hloov pauv nyiaj ntau dua 80% 12 % ntawm txhua qhov kev hloov pauv KRAS, thiab feem ntau yog cov mob qog noj ntshav uas tsis yog me me (NSCLC).

KRAS G12C inhibitors tuaj yeem txuas covalently rau KRAS nrog G12C kev hloov pauv thiab kaw KRAS G12C hloov pauv hauv lub xeev tsis ua haujlwm. Txoj kev kho no thawj zaug ua tiav qhov kev kov yeej loj hauv Amgen' s AMG 510 inhibitor. AMG 510 tau tsom mus rau NSCLC. Nws tau txais kev pom zoo kho los ntawm FDA thaum kawg ntawm 2020, thiab tau tsim nyog rau kev tshuaj xyuas ua ntej thiab nrawm pom zoo. Nws tau pom zoo los ntawm FDA rau 28th los ua lub ntiaj teb' thawj KRAS inhibitor.

Ntxiv nrog rau kev tsom ncaj qha rau RAS kev kho mob, kev kho lub hom phiaj ncaj qha kuj tseem nyiam mloog. Kev kho tus kheej tsis ncaj ncees feem ntau txwv tsis pub lub hom phiaj hauv nws txoj hauv kev taw qhia kom tiv thaiv kev sib xyaw ntawm RAS thiab GTP los ntawm kev nkag mus rau lub xeev qhib, yog li zam kev pib ua rau mob qog noj ntshav. Cov tuam txhab muag tshuaj tau koom ua ke hauv txoj kev tshawb fawb no thiab txoj kev txhim kho, vam tias yuav tau txais cov txuj ci thev naus laus zis.

Tam sim no, Novartis' s TNO-155, JAB-3068 sib koom tsim los ntawm Jacos thiab AbbVie, thiab RMC-4630 sib koom tsim los ntawm Sanofi thiab Kev Hloov Pauv yog txhua qhov kev twv ntawm SHP2 inhibitor khiav thiab tau nkag mus rau theem kuv qhov kev sim tshuaj ; Roche' s Cobimetinib, Novartis&#Trametinib thiab Array' s Binimetinib yog txhua tus MEK inhibitors. Ntawm lawv, Array' s Encorafenib thiab Binimetinib tau siv ua ke los kho mob qog noj ntshav melanoma; Bayer' s Copanlisib lub hom phiaj PI3K teeb tsa txoj hauv kev, thaum lub Cuaj Hlis 2017 Nws tau pom zoo los ntawm Asmeskas FDA rau hnub tim 14 rau kev kho mob qog noj ntshav qog noj ntshav rov qab los, thiab tau suav nrog hauv cov npe khoom kho mob los ntawm CDE ntawm kawg ntawm 2020, thiab tau tshaj tawm rau npe hauv Suav teb.

Ntxiv rau kev tsom mus rau RAS ncaj qha thiab lub hom phiaj ncaj qha ntawm RAS, muaj ntau txoj kev kho rau RAS hloov pauv, xws li siRNA txoj kev kho, txais kev kho mob ntawm tus menyuam, thiab txhaj tshuaj tiv thaiv qog, tos rau kev tshawb fawb tshawb fawb thiab pov thawj.