Izidakamizwa ezigunyazwe yi-ASCO kusukela ngo-2005 kuya ku-2014
Kusukela i-ASCO yashicilela umbiko wayo wokuqala wokuqhubekela phambili komdlavuza ngo-2005, ibone inqubekelaphambili eqinile futhi enqunyiwe emkhakheni we-oncology eminyakeni eyi-10 edlule.
Eminyakeni eyi-10 edlule, izidakamizwa ezilwa nesimila ezingaphezu kuka-60 zigunyazwe yi-FDA (Umfanekiso 1). Ngokuqonda okujulile kwe-tumor biology, ososayensi benze uchungechunge lwemithi emisha eqondiswe kumangqamuzana, futhi ukufika kwabo kushintshe ngezinkulungwane. Isimo samashumi ezinkulungwane zeziguli ezinomdlavuza okunzima ukuzelapha.
Such new drugs can target specific molecules or molecular clusters necessary for isisu cell growth, survival or spread.
Eminyakeni eyishumi edlule, iNational Institutes of Health yethula iphrojekthi ye-TCGA, eyaba ngeyokuqala futhi ebanzi kakhulu yamaphrojekthi anjalo. Kuze kube manje, inethiwekhi yocwaningo ye-TCGA iveze imephu yamangqamuzana ephelele yezinhlobo zomdlavuza eziyi-10.
Namuhla, i-TCGA namanye amaphrojekthi okulandelana kwemiphumela ephezulu ayaqhubeka nokuhlola ulwazi olubalulekile oluzosiza ukuthuthukisa ukubikezela kwesiguli ngochungechunge lwezindlela. Kungenzeka ukuthi iziguli zikhethe indlela yokwelapha efaneleke kakhulu. Ucwaningo luphinde lwathola ukungalungi kofuzo olusha lomshayeli womdlavuza. Lezi zakhi zofuzo zingase zibe yizisulu zemithi emisha.
Ngemuva kwamashumi eminyaka okuthuthukiswa okuqhubekayo, insimu yama-antibody immunotherapy has finally ushered in the long-awaited major success in recent years. It first occurred in the treatment of advanced melanoma, followed by a series of other cancer types, including lung cancer. Common types have also made progress.
Isibalo seziguli ebezikade zingenazo izindlela zokwelapha ezisebenzayo zaphila isikhathi eside kakhulu ngemva kokwelashwa ngemithi emisha. Ucwaningo lwakamuva lwesikhathi eside luphakamise ukuthi i-antibody immunotherapy isenawo umthelela ekukhuleni kwesimila ngemva kweminyaka eminingi yokwelashwa.
Olunye uhlobo lwe-immunotherapy luzibophezele ekuhleleni kabusha amangqamuzana alo omzimba ukuze ahlasele amaseli e-tumor. Isebenza kahle futhi kumathumba egazi athile kanye nochungechunge lwamathumba aqinile.
Okokuqala umuthi wokugomela umdlavuza kule minyaka eyishumi eyedlule iphinde yakhululwa (umuthi wokugomela umdlavuza womlomo wesibeletho i-Gardasil). Ukuhlolwa kokuhlola ezinye izinhlobo zemithi yokugomela umdlavuza nakho kuyaqhubeka.
Finally, large-scale screening studies have brought new and important evidence that it can advance screening practices for some common cancers such as lung cancer, breast cancer, and umdlavuza wendlala.
Ukuthuthukiswa okusheshayo kokwelashwa okuhlosiwe ekwelapheni umdlavuza
Eminyakeni eyishumi edlule, sibone ukwanda okuqhubekayo nokushesha kwenani lemithi yokwelapha ehlosiwe egunyazwe yi-FDA, edlula kude isivinini sokuthuthukiswa kwemithi emisha yokwelapha ngamakhemikhali (Umfanekiso 2).
Ngalesi sikhathi, kwavunywa imithi emisha ehlosiwe engaba ngu-40, eminingi yayo eyashintsha imodeli yokwelapha yendabuko futhi yathuthukisa kakhulu ukubikezelwa kweziguli eziningi ezinomdlavuza.
Okokuqala sethula ama-anti-angiogenesis inhibitors, okuyikilasi lemithi eklanyelwe ukunciphisa i-neovascularization yamathumba futhi abe ukwelapha okuphumelelayo komdlavuza omningi osethuthukile nonolaka.
The first drug approved by the FDA is bevacizumab, which was approved for advanced colorectal cancer in 2004 and has since been used in certain lung, kidney, ovarian, and brain tumors.
Subsequently, other angiogenesis inhibitor drugs such as axitinib, carbotinib, pazopanib, rigefenib, sorafenib, sunitinib, vandetanib, and abecept were successively Approved for the treatment of advanced kidney cancer, pancreatic cancer, colorectal cancer, thyroid cancer, and izimila stromal emathunjini and sarcomas.
I-EGFR inhibitors: iqondise izindlela zokusayina ezibalulekile
Izimila Nemithambo yegazi
Esinye isigaba esikhulu sezidakamizwa ezihlosiwe senzelwe ukuphazamisa izindlela ezibucayi zokubonisa kumaseli, ikakhulukazi inethiwekhi yokubonisa elawula ukukhula kwamangqamuzana omdlavuza. Enye yalezi zindlela ilawulwa amaprotheni e-EGFR.
The first EGFR drug was gefitinib, which was approved for the treatment of NSCLC in 2003. Two years later, the FDA approved the second EGFR drug cetuximab for the treatment of advanced umdlavuza colorectal, and another similar drug panitumumab was also approved in 2006.
Kodwa-ke, ngo-2008, ucwaningo olusha lwembula ukuthi iziguli ezinomdlavuza we-colorectal ezinezinguquko ze-KRAS zaqala ukumelana ne-cetuximab ne-panitumumab. Lokhu kutholakala kudinga ukuhlolwa okujwayelekile kokuguqulwa kwezakhi zofuzo ze-KRAS ukuze kuqinisekiswe ukuthi iziguli zingazuza ekwelashweni kwezidakamizwa ezimbili ezingenhla, kuyilapho kuvikela ezinye iziguli emiphumeleni emibi yokwelashwa okungenalusizo.
In 2004 and 2005, the FDA approved the EGFR inhibitor erlotinib for the treatment of NSCLC and advanced umdlavuza pancreatic. Recently, in 2013, the US FDA approved afatinib for the treatment of advanced NSCLC patients with specific mutations in the EGFR gene. Other EGFR targeted drugs are undergoing clinical trials.
New HER2 therapy brings continuous breakthrough in umdlavuza webele ukwelashwa
Cishe eminyakeni eyi-15 eyedlule, ososayensi bathola ukwelashwa kokuqala kwezicubu zesimila ezicindezela kakhulu i-epidermal growth factor receptor 2 (HER2). Cishe i-15% kuya ku-20% yeziguli ezinomdlavuza webele zithwala okungenhla okungavamile kofuzo (HER2-positive cancer). Ngokufanayo ne-EGFR yomndeni ofanayo, i-HER2 ingaphinde ikhuthaze ukukhula kwamangqamuzana omdlavuza. Kusukela lapho, kuye kwazalwa imithi emine ehloselwe i-HER2, yonke engathuthukisa ukuphila kweziguli ezinomdlavuza webele we-HER2.
Umuthi wokuqala we-HER2, i-trastuzumab, lapho usetshenziswa uhlanganiswe nokwelashwa ngamakhemikhali ungathuthukisa kakhulu ukusinda kwabesifazane abanomdlavuza webele osuthuthukisiwe we-HER2. Ngo-2006, i-trastuzumab yagunyazwa ezigulini ezinomdlavuza webele wokuqala one-HER2-positive ukuze kwehliswe ingcuphe yokuphinda iphindeke ngemva kokuhlinzwa.
Muva nje, ucwaningo olubalulekile luthole ukuthi ukushaya okuphindwe kabili kwe-HER2 kusebenza kangcono kune-trastuzumab monotherapy, okuholele ekugunyazweni kwe-FDA komuthi wesibili we-HER2 i-Pertuzumab ngokuhlangana ne-trastuzumab ngo-2012 i-Monoclonal antibody isetshenziswa ezigulini ezinomdlavuza webele osuthuthukisiwe we-HER2. , wabe esegunyazwa ukwelashwa kwezifo zakuqala ngo-2013.
Ngawo lowo nyaka, i-trastuzumab-emtansine (T-DM1) (trastuzumab ehlanganiswe nomuthi we-chemotherapeutic) nayo yavunywa. Lokhu kwelashwa okuhlangene akusebenzi nje kuphela kunokwelashwa kwezidakamizwa okukodwa, kodwa futhi kuvumela umuthi ukuthi uqondiswe ngokunembile kumaseli omdlavuza webele, ngaleyo ndlela unciphise imiphumela emibi kumaseli ezicubu ezinempilo. Ngomdlavuza webele we-HER2 one-HERXNUMX oye wawohloka ngemva kokwelashwa okuningi kwangaphambilini, lolu wuhlelo lokwelapha olufanele.
Umuthi wesine we-HER2, i-lapatinib, wavunywa ngo-2007. Uma usetshenziswa ngokuhambisana nezidakamizwa ze-aromatase inhibitor, ungelapha ngempumelelo i-HER2-positive kanye ne-hormonal receptor-positive / HER2-positive metastatic umdlavuza webele.
Izidakamizwa eziqondise izindlela eziningi zamangqamuzana: amathemba athembisayo
Researchers continue to find that many cancer drugs can block multiple molecular targets or pathways at the same time, which makes them a more effective anti-cancer weapon. For example, vandetanib (approved for the treatment of umdlavuza we-thyroid in 2011) can Block EGFR, VEGFR (protein involved in tumor blood vessel growth) and RET.
Umuthi womdlavuza we-colorectal i-gefitinib (wavunywa ngo-2012) uvimba izindlela ezi-6 ezihlukene zomdlavuza: i-VEGFR1-3, TIE2, PDGFR, FGFR, KIT, ne-RET.
Okuhlosiwe okusha nemithi emisha ekwelapheni umdlavuza
I-prospec
I-ts yokuthuthukiswa kwezidakamizwa emisha iyathandeka kakhulu. Ngo-2013 nango-2014, i-FDA igunyaze i-Trametinib ne-Dalafenib, izidakamizwa ezimbili ezingasetshenziswa ukwelapha i-melanoma ethile eguquguqukayo yofuzo lwe-BRAF, elawula indlela ye-MEK.
Crizotinib (approved in 2013) can target umdlavuza wamaphaphu and childhood cancer with ALK gene mutation. Tisirolimus (approved in 2007) and everolimus (approved in 2012) block the mTOR pathway, which can control the growth of several cancers, including breast cancer, pancreatic cancer, and kidney cancer.
I-Everolimus umuthi wokuqala ohlosiwe osebenzayo womdlavuza webele we-HER2-negative, lolu hlobo lubanga umdlavuza webele omningi. I-Everolimus ehlanganiswe nezidakamizwa ze-aromatase inhibitor igunyazwe i-hormone receptor positive kanye ne-HER2 negative postmenopausal iziguli ezinomdlavuza webele othuthukile.
I-Nilotinib (yavunywa ngo-2007) kanye ne-dasatinib (eyagunyazwa ngo-2010) ingaqondisa i-BCR-ABL, iphrotheni ethile etholakala kuphela ezinhlotsheni ezithile ze-leukemia.
Siyakwamukela enkathini ye-immunotherapy
Ososayensi bazi ukuthi isimiso somzimba sokuzivikela ezifweni singamandla anamandla okulwa nomdlavuza eminyakeni eyikhulu edlule. Kodwa kuze kube yiminyaka eyishumi edlule lapho i-immunotherapy yaqala ngempela ukuguqula ukwelashwa komdlavuza. Inqubekelaphambili yenziwe ngezindlela eziningana kusukela emithini yomlomo kuya ekwelapheni okusekelwe kumaseli okuklanyelwe isiguli ngasinye.
Khuthaza amasosha omzimba ukuze alwe nomdlavuza
Ama-T cell adlala indima ebalulekile ekulweni nomdlavuza. Ngo-2011, i-FDA igunyaze i-ipilimumab njengendlela yokwelapha ephumelelayo ye-melanoma. I-Ipilimumab iyisidakamizwa sokuzivikela komzimba esiqondise kuphrotheni ye-CTLA-4 yamaseli e-T, engavimbela umphumela wokubulala wama-T cell.
Ezivivinyweni zomtholampilo, iziguli zizobhekana nokuhlehla kwesimila ngokushesha nokusobala, futhi zisazozuza ngemva kwesikhathi eside ngemva kokuphela kokwelashwa (kwezinye iziguli kungase kuhlale iminyaka eminingana).
Kusukela lapho, kuye kwasungulwa ezinye izidakamizwa ezibizwa nge-immune checkpoint inhibitor, ikakhulukazi ezinye izidakamizwa zingakhomba indlela ye-PD-1 / PD-L1, esiza amathumba ukubaleka amasosha omzimba.
I-FDA iklomelise izidakamizwa ze-PD-1 blocker nivolumab kanye ne-MK-3475 izihloko zokwelapha eziphumelelayo. Ezivivinyweni zakamuva zomtholampilo ze-melanoma, zombili zibonise ukusebenza kahle ngendlela engakaze ibonwe ngaphambili (i-nivolumab ingasetshenziswa ngempumelelo kumdlavuza wezinso Kanye nokwelashwa komdlavuza wamaphaphu).
NgoSepthemba 2014, i-Mk-3475 (pembrolizumab) yaba umuthi wokuqala oqondiswe ku-PD-1 owavunywa yi-FDA. Isidakamizwa esiqondiswe ku-PD-1 i-MPDL3280A siphinde sabonisa umphumela ngokumelene ne-melanoma ethuthukisiwe ezivivinyweni zomtholampilo.
Ucwaningo lwakamuva lubonisa ukuthi ukusetshenziswa okuhlangene kwemithi ehlukene yokuhlola inhibitor noma inhlanganisela yezidakamizwa ezisebenza ngokuzivikela ezifweni ezifana ne-interferon, i-interleukin nezinye izidakamizwa ze-checkpoint inhibitor kungase kuthuthukise inzuzo yesiguli.
Patients and abasindile have significantly improved quality of life
Kule minyaka eyishumi edlule, ucwaningo luthole uchungechunge lwezindlela zokwelapha ezintsha ezingathuthukisa ikhwalithi yempilo yeziguli kuzo zonke izinyathelo ukusuka ekuxilongweni kuya ekusindeni. Ukwengeza, ukugcizelela ukuhlanganiswa kokunakekelwa kwe-palliative kusenesikhathi kanye nokwelashwa okusebenzayo kuzosiza iziguli eziningi, ikakhulukazi ukukhuthaza iziguli ezithuthukile ukuze ziphile impilo engcono.
Yehlisa imiphumela emibi ehlobene nomdlavuza
Amasu amasha ahloselwe ukulawula imiphumela emibi angathuthukisa kakhulu izinga lempilo yeziguli, phakathi nangemuva kokwelashwa. Isibonelo, ucwaningo olubili oluzimele lubonise ukuthi i-antidepressant duloxetine kanye ne-antipsychotic olanzapine imithi esebenzayo yokuvimbela imiphumela emibi evamile efana ne-chemotherapy peripheral neuropathy kanye nesicanucanu.
Olunye ucwaningo lwathola ukwelashwa kwezimpawu ezivamile ezingazange zidonse ukunakwa okwanele-ukucindezeleka nobuhlungu. Ubufakazi obuningi buqinisekisa ukusebenza kwezindlela okungezona ezokwelashwa ezifana ne-acupuncture ne-yoga ukuthuthukisa impilo yomzimba nengqondo yeziguli nabasindile. Izinzuzo ezingaba khona zihlanganisa ukunciphisa ukukhathala nobuhlungu, ukuthuthukisa izinga lempilo, nokunciphisa ukusetshenziswa kwemithi.
Ukuhlanganisa ukwelashwa komdlavuza nokunakekelwa kwangaphambi kwesikhathi kwe-palliative
Ukuhlolwa komtholampilo okubalulekile ngo-2010 kwaqinisekisa ukuthi ukuhlanganiswa kokwelashwa okudambisa izinhlungu kusenesikhathi ngesikhathi sokwelashwa kungathuthukisa kakhulu izinga lempilo futhi kwandise ukuphila kweziguli ezinomdlavuza wamaphaphu othuthukisiwe uma kuqhathaniswa nokwelashwa okukodwa okusebenzayo. Ukwengeza, iziguli ezithole ukunakekelwa kwe-palliative kusenesikhathi akulindelekile ukuthi zithole ukunakekelwa okunamandla okusebenzayo okufana nokuvuselelwa ekupheleni kokuphila.
Ucwaningo ludale igagasi elisha lokunakekelwa kweziguli ezithuthukile. Ucwaningo luphinde lwasho izincomo zezinkombandlela zesikhashana ezikhishwe yi-ASCO ngo-2012: Noma yisiphi isiguli esinomdlavuza we-metastatic noma umthwalo wezimpawu ophakeme singahambisana nokwelashwa kwe-palliative ekwelashweni komdlavuza okujwayelekile kwangaphambi kwesikhathi.
Izidakamizwa ezivamile ezinciphisa ingozi yomdlavuza
A large number of clinical trials have shown that some commonly used drugs may have important effects on cancer prevention. For example, analysis of data from nearly 50 epidemiological studies shows that oral contraceptives can reduce the risk of ovarian cancer by 20% every 5 years. This reduction effect persists within 30 years of termination of the drug.
Ucwaningo olwengeziwe lwathola ukuthi ukuphuza i-aspirin nsuku zonke kunganciphisa ingozi yomdlavuza we-colorectal. Nokho, ngenxa yokopha esiswini nezinye izingozi, akunconywa ukusebenzisa i-aspirin ngokujwayelekile njengendlela yokuvimbela umdlavuza. Isinyathelo esilandelayo socwaningo sizophinde sihlole imishanguzo eqeda ukuvuvukala ekuvimbeleni umdlavuza kanye nendima yokwelapha.
