Onvansertib muaj txiaj ntsig zoo hauv kev kho KRAS mutant mCRC: tag nrho cov lus teb yog 42%!--1/2

Dr. Mark Erlander, Tus Thawj Saib Xyuas Haujlwm ntawm Cardiff Oncology, tau hais tias:" Cov teeb liab muaj zog ntawm kev ua tau zoo thiab kev zam zoo tau pom nyob rau hauv kev sim tshuaj ntsuam xyuas zoo rau peb txoj haujlwm mCRC thiab txhua qhov ntawm peb cov kev pabcuam kho mob KRAS. Piv nrog rau pawg tswj hwm keeb kwm, qhov kev txhim kho tseem ceeb uas peb tau pom hauv kev kho cov lus teb qhia tau hais tias muaj txiaj ntsig ntawm kev sib xyaw ua ke thiab txhawb kev sib ntxiv ntawm onvansertib rau FOLFIRI (irinotecan thiab 5-FU) cov txheej txheem tau pom nyob rau hauv cov kev tshawb fawb preclinical Synergistic cuam tshuam hauv txoj kev kho mob. Peb kuj tau pom cov txiaj ntsig biomarker tseem ceeb, qhia txog qhov muaj peev xwm siv hluav taws xob ntawm cov ntshav ntshav KRAS MAF ua cov cuab yeej kwv yees, uas tuaj yeem pab ua raws li kev sim tsim. Saib tom ntej, peb cia siab tias yuav txuas ntxiv mus rau Theem 2 qhov kev sim tshuaj ntxiv Cov ntaub ntawv ntxiv yuav raug muab los txhawb kev kho mob ntawm onvansertib, tsim kom muaj nuj nqis rau cov tswv cuab, thiab qhov tseem ceeb tshaj, muab kev kho tshiab rau cov neeg mob."

onvansertib chemical qauv

onvansertib yog qhov ncauj, xaiv Polo-zoo li kinase 1 (PLK1) inhibitor. Nws yog tam sim no tau tsim los ua ke nrog cov qauv kev kho mob kom kov yeej cov kev kho mob tam sim no thiab txhim kho kev ua tau zoo ntawm cov qog nqaij hlav thiab cov qog hematological. Thiab tag nrho cov ciaj sia taus.

PLK1 yog lub hom phiaj kho mob uas muaj pov thawj thiab muaj ntau dhau ntawm cov qog nqaij hlav. PLK1 yog ib qho serine / threonine kinase thiab tus tswj hwm loj ntawm kev hloov pauv ntawm tes. PKL1 tswj qhov chaw kuaj G2/mitotic (G2/M). Inhibition ntawm PLK1 tuaj yeem ua rau mitotic ntes thiab tom qab cell tuag. Cov ntaub ntawv tshiab qhia tau hais tias PLK1 kuj yog ib qho tseem ceeb regulator sab nraum mitosis thiab yog ib qho tseem ceeb rau cov qog loj hlob, xws li DNA puas teb.

Hais txog mCRC, onvansertib tsuas yog PLK1 inhibitor thiab tsom rau kev kho mob hauv kev kho mob. Nws tau pom tias muaj zog tiv thaiv KRAS kev hloov pauv hauv mCRC uas hnyav thiab nyuaj kho nrog tshuaj. KRAS mutant hlwb yog rhiab heev rau PLK1 inhibition. RAS qhib PLK1 los ntawm MEK / ERK ywj pheej mechanism. Downstream CRAF cuam tshuam nrog PLK1 thiab txhawb nqa PLK1 ua kom, ua rau mitosis thiab qog nqaij hlav.

Onvansertib muaj cov nyhuv synergistic nrog irinotecan thiab 5-FU, thiab cov tshuaj sib xyaw ua ke muaj kev cuam tshuam ntau zog ntawm cov qog loj hlob dua li cov tshuaj ib leeg. Kwv yees li 50% ntawm mCRCs muaj feem xyuam nrog KRAS kev hloov pauv uas nyuaj rau kho. Nws ntseeg tias KRAS kev hloov pauv tuaj yeem ua rau muaj kev loj hlob ntawm cov qog nqaij hlav thiab tiv thaiv cov kev kho mob uas twb muaj lawm. Onvansertib muaj peev xwm muab kev cog lus tshiab kev kho mob rau KRAS mutant mCRC.