Sida lagu sheegay warbixintii ugu dambeysay ee ka soo baxday Xarumaha Xakamaynta iyo Kahortagga Cudurrada ee Maraykanka (CDC), dhacdooyinka ku dhowaad dhammaan kansarrada ayaa hoos u dhacay labaatankii sano ee la soo dhaafay, halka dhacdooyinka kansarka ilma -galeenku kor u kaceen. Dhakhaatiirtu waxay bilaabeen inay fiiro gaar ah u yeeshaan xaaladdan waxayna xusuusiyeen haweenka inay fiiro gaar ah u yeeshaan dhowr arrimood oo muhiim u ah cudurkan.
According to statistics from the American Cancer Society (ACS), more than 90% of uterine cancers occur in the endometrium, called endometrial cancer. Early endometrial cancer has a good prognosis. According to the US Centers for Disease Control and Prevention, the five-year relative survival rate is estimated to be 80% to 90%. Because kansarka ilmo galeenka can usually be diagnosed early, its most typical symptoms are abnormal bleeding before and after menopause, weight loss and pelvic pain. For advanced metastatic patients, treatment options are very limited.
Dhowaan, US FDA waxay ansixisay PD-1 inhibitor Keytruda (pabolizumab) oo ay weheliso tyrosine kinase inhibitor Lenvima (Levatinib) si loogu daweeyo bukaannada qaba kansarka endometrial gaar ah. Waxaa mudan in la ogaado in bukaannadani aysan u baahnayn xasillooni darro sare oo microsatellite ah (MSI-H) ama cilladda dayactirka (dMMR). Ilaa inta uu cudurku sii wado horumarka ka dib marka la helo daawaynta habdhiska hore oo aan la heli karin qaliin daawaynta ama shucaaca, daawaynta cusub ee isku dhafka ah waa la aqbali karaa.
Waa in la sheegaa in oggolaanshahan la dedejiyey lagu oggolaaday isku mar Maraykanka, Australia iyo Kanada.
Ansixinta waxay ku saleysan tahay natiijooyinka daraasad lagu sameeyay 94 bukaan oo qaba burooyinka kansarka endometrial, oo aan midkoodna ahayn MSI-H ama dMMR. Bukaanadan, wadarta guud ee jawaabta (ORR) waxay ahayd 38.3%, oo ay kujiraan 10.6% heerka jawaabta oo dhameystiran (CR) iyo heerka jawaabta qeyb ahaan 27.7%. 69% (n = 25) bukaanku waxay lahaayeen mudada jawaabta (DOR) months 6 bilood.
“Ugu yaraan 75% bukaanada qaba kansarka endometrial ma ahan kuwa MSI-H ama nooca dMMR, marka ansixinta daaweyntan waxay keeneysaa ikhtiyaarro daaweyn cusub waxayna rajo u qabaan bukaanada badankood ee qaba kansarka endometrial.
Waqtigan xaadirka ah, horumarka kale ee cilmi baarista ee kansarka endometrial ayaa sidoo kale halkan si kooban loogu soo bandhigay:
01avelumab (Bavincia monoclonal antibody) oo lagu daray talazoparib (tarazopanib)
Maxkamad uu hogaaminayo Konstantinopoulos ayaa adeegsaday avelumab isdifaaca isdifaaca isdifaaca iyadoo lagu darayo PARP inhibitor talazoparib. (Kontaroolayaasha isbaarooyinka dhigaa waxay nadiifiyaan wadada habka difaaca jirka u weeraraan kansarka; PARP ka hortagayaashu waxay baabi'iyaan unugyada kansarka iyagoo hor istaagaya awoodooda inay dayactiraan DNA-da dhaawacan.) Tijaabadii hore, avelumab waxay ahayd Bukaanka qaba kansarka "aan xasilooneyn" endometrial waa waxtar badan, laakiin asal ahaan aan firfircooneyn ee nooca cudurka "microsatellite deggan" (MSS) ee caanka ah. Tijaabadu waxay sahmineysaa in isku darka avelumab iyo ka hortagayaasha PARP ay waxtar badan u leedahay bukaanada qaba cudurka MSS.
02pembrolizumab (pabolizumab) oo lagu daray mirvetuximab
Tijaabo isku daraysa barta koontaroolka ee pembrolizumab iyo mirvetuximab. (Pembrolizumab waxay beegsataa borotiinka isbaarada difaaca ee loo yaqaan PD-1; mirvetuximab waxay ku darsataa unugyada ka-hortagga molecules-ka daroogada ee beegsanaya qaababka muhiimka ah ee unugyada kansarka si degdeg ah u kala qaybiya. bukaanka qaba kansarka endometrial MSS.
03abemaciclib + LY3023414 + daaweynta hoormoonka
Tijaabo kale oo uu hogaaminayo Konstantinopoulos ayaa tijaabin doonta isku darka daroogada abemaciclib + LY3023414 + therapy hormone. (LY3023414 wuxuu bartilmaameedsanayaa unugyada kansarka ee loo yaqaan PI 3 kinase; abemaciclib wuxuu farageliyaa marxaladda muhiimka ah ee wareegga unugga.) 70% ilaa 90% ee kansarka endometrial waxaa lagu quudiyaa estrogen waxayna marka hore ka jawaabaan daaweynta hormoonka xannibaadda, laakiin ugu dambeyntii soo noqoshada. Ku darista abemaciclib iyo LY3023414 (waxay taaban karaan laba qaybood oo isla dariiqa molikal ah) ee daaweynta hormoonka xannibaadda, cilmi baarayaashu waxay rajaynayaan inay ka adkaadaan dhibaatada iska caabinta daroogada.
04AZD1775
A trial led by Joyce Liu, MD, MPH, director of clinical research at the Department of Gynecologic Oncology at Dana-Farber, used AZD1775 for patients with high-grade serous uterine cancer that account for 10-15% of endometrial cancer. Such cancers are aggressive and usually recur after standard treatment. The recently opened trial is based on a study led by Dr. Liu and Ursula Matulonis, director of the Dana-Farber Department of Gynecologic Oncology, showing that AZD1775 is active in a patient model with high-grade serous kansarka ugxansiduhu.
05dostarlimab (TSR-042)
Natiijooyinka tijaabada Wajiga I / II ee GARNET ayaa dhowaan la daabacay, iyo guud ahaan heerka waxtarka leh ee PD-1 inhibitor dostarlimab (TSR-042) ee bukaannada qaba soo noqnoqda ama kansarka endometrial wuxuu ku dhow yahay 30%.
Intaas waxaa sii dheer, xasillooni darrada micro-satellite-ka (MSI-H) iyo kooxaha xasilloonida yar-yar (MSS) waa kuwo joogto ah.
Dostarlimab (TSR-042) waa antibody-anti-PD-1 monoclonal antibody oo ay si wada jir ah u soo saareen TESARO iyo AnaptysBio. Waxay ku xidhan tahay soo-qaadaha PD-1 oo leh xidhiidh sare, taas oo ka dhigaysa inay ku xirto xirmooyinka PD-L1 iyo PD-L2.
Natiijooyinka waxay muujiyeen in heerka wax ku oolka ah ee dadweynaha oo dhan uu ahaa 29.6%, heerka wax ku oolka ah ee kooxda bukaanka MSI-H wuxuu ahaa 48.8%, iyo heerka wax ku oolka ee kooxda MSS wuxuu ahaa 20.3%. Lix bukaan (2 MSI-H iyo 4 MSS) ayaa dhammeystiray dhammaystirka.
Kadib dabagal dhexdhexaad ah oo 10 bilood ah, 89% bukaanada waxay heleen daaweyn> 6 bilood, iyo 49% bukaanada waxay heleen daaweyn> 1 sano. Intaas waxaa sii dheer, 84% bukaanada wax ku oolka ah daaweynta ayaa wali helaya daaweyn.
Finally, in 85% of MSI-H responders, the total buro burden was reduced by ≥50%, and 69% of patients with MSS had a total tumor burden of ≥50%.
Dostarlimab waa rajo cusub oo loogu talagalay daaweynta kansarka endometrial.
Cilmi-baarayaashu waxay bilaabi doonaan daraasado dheeraad ah oo III ah qaybta labaad ee 2019. Dostarlimab iyo chemotherapy ayaa lagu dari doonaa daaweynta safka hore ee kansarka endometrial, waxaana rajeyneynaa inaan helno natiijooyin rajo leh dhawaan!
Tijaabad kasta waxay wax ka qabtaa cilladaha daaweynta caadiga ah ama dhibaatooyinka laga helay tijaabooyinkii hore ee dawooyinka cusub. Tusaale ahaan, labada tijaabo ee hore waxaa looga dan leeyahay sidii looga gudbi lahaa xaaladda faqiirka ee hadda jirta immunotherapy bukaanka qaba cudurka MSS. Midda saddexaad waxay xallisaa dhibaatada iska caabbinta daaweynta hoormoonka, kan afraadna wuxuu bartilmaameedsanayaa noocyada gaarka ah ee kansarka endothelial.
Si aad wax badan uga ogaato horumarka cilmi-baarista ee ugu dambeeyay iyo qorshaha daaweynta ugu fiican ee kansarka endometrial, kaliya khabiirada kansarka ugu sarreeya ee gudaha iyo dibaddaba ayaa leh khibrad caafimaad oo hodan ah. Waxaad dalban kartaa la-talin lala yeesho khubarada ku xeel dheer arrimaha gudaha iyo kuwa caalamiga ah si aad u hesho cudurka ugu fiican iyo qorshaha daaweynta.
