litaba

Lilemong tse leshome tse fetileng, theknoloji ea tatellano ea liphatsa tsa lefutso e sebelisitsoe haholo lipatlisisong tsa mofetše le boikoetliso ba bongaka, e fetoha sesebelisoa sa bohlokoa ho senola litšobotsi tsa limolek'hule tsa mofets'e. Tsoelo-pele ea tlhahlobo ea limolek'hule le kalafo e tobisitsoeng e khothalelitse nts'etsopele ea mehopolo ea kalafo e nepahetseng ea tumor mme e tlisitse liphetoho tse kholo lefapheng lohle la tlhahlobo le kalafo ea hlahala. Teko ea liphatsa tsa lefutso e ka sebelisoa ho hlokomelisa kotsi ea mofetše, ho tataisa liqeto tsa kalafo le ho lekola bokuli, 'me ke sesebelisoa sa bohlokoa sa ho ntlafatsa litlamorao tsa mokuli. Mona, re akaretsa lihlooho tsa morao-rao tse hatisitsoeng ho CA Cancer J Clin, JCO, Ann Oncol le likoranta tse ling ho hlahloba ts'ebeliso ea tlhahlobo ea liphatsa tsa lefutso ho hlahloba kankere le kalafo.

Liphetoho tsa Somatic le liphetoho tsa germline. Ka kakaretso, kankere e bakoa ke liphetoho tsa DNA tse ka futsoang ho batsoali (liphetoho tsa likokoana-hloko) kapa tse fumanoang ka lilemo (liphetoho tsa somatic). Liphetoho tsa likokoana-hloko li teng ho tloha tsoalong, 'me phetoho e atisa ho jara phetoho ea DNA ea sele e' ngoe le e 'ngoe ea' mele 'me e ka fetisetsoa ho bana. Liphetoho tsa Somatic li fumanoa ke batho ba lisele tse seng tsa papali 'me hangata ha li fetisetsoe ho bana. Liphetoho tse peli tsa germline le somatic li ka senya ts'ebetso e tloaelehileng ea lisele mme tsa lebisa phetohong e mpe ea lisele. Liphetoho tsa Somatic ke sesosa se ka sehloohong sa ho baka bobe le biomarker e boletsoeng esale pele ho oncology; leha ho le joalo, hoo e ka bang karolo ea 10 ho isa ho 20 lekholong ea bakuli ba hlahala ba na le liphetoho tsa likokoana-hloko tse eketsang kotsi ea mofetše haholo, 'me tse ling tsa liphetoho tsena le tsona ke tsa phekolo.
Phetoho ea mokhanni le phetoho ea bapalami. Ha se mefuta eohle ea DNA e amang tšebetso ea lisele; ka karolelano, ho nka liketsahalo tse hlano ho isa ho tse leshome tsa genomic, tse tsejoang e le "liphetoho tsa mokhanni," ho qala ho senyeha ho tloaelehileng ha lisele. Liphetoho tsa mokhanni li atisa ho etsahala liphatseng tsa lefutso tse amanang haufi-ufi le mesebetsi ea bophelo ba lisele, tse kang liphatsa tsa lefutso tse amehang taolong ea kholo ea lisele, ho lokisoa ha DNA, taolo ea potoloho ea lisele le mekhoa e meng ea bophelo, 'me e na le monyetla oa ho sebelisoa e le lipakane tsa phekolo. Leha ho le joalo, palo eohle ea liphetoho mofetšeng ofe kapa ofe e kholo haholo, ho tloha ho likete tse 'maloa ho tse ling tsa mofetše oa matsoele ho isa ho tse fetang 100,000 ho tse ling tsa mofets'e oa colorectal le endometrial. Liphetoho tse ngata ha li na kapa li na le bohlokoa bo fokolang ba tlhaho, leha phetoho e etsahala sebakeng sa likhoutu, liketsahalo tse joalo tse sa reng letho tsa phetoho li bitsoa "liphetoho tsa baeti". Haeba phapano ea lefutso mofuteng o itseng oa hlahala e bolela esale pele karabelo ea eona kapa ho hana kalafo, mofuta ona o nkuoa o sebetsa ka mokhoa oa bongaka.
Liphatsa tsa lefutso tsa oncogenes le tumor suppressor. Liphatsa tsa lefutso tse atisang ho fetoloa mofetšeng li ka aroloa ka mekhahlelo e 'meli, liphatsa tsa lefutso tsa oncogene le liphatsa tsa lefutso. Liseleng tse tloaelehileng, protheine e kentsoeng ke li-oncogenes e bapala karolo ea ho khothaletsa ho ata ha lisele le ho thibela apoptosis ea lisele, athe protheine e kentsoeng ke liphatsa tsa lefutso tsa oncosuppressor e ikarabella haholo bakeng sa ho laola karohano ea lisele hampe ho boloka tšebetso e tloaelehileng ea lisele. Ts'ebetsong e mpe ea phetoho, phetoho ea genomic e lebisa ntlafatsong ea ts'ebetso ea oncogene le ho fokotseha kapa tahlehelo ea ts'ebetso ea liphatsa tsa lefutso tsa oncosuppressor.
Phapang e nyane le phapang ea sebopeho. Ena ke mefuta e 'meli e meholo ea liphetoho tse teng ho genome. Mefuta e nyane e fetola DNA ka ho fetola, ho hlakola, kapa ho eketsa palo e nyane ea metheo, ho kenyelletsa ho kenya, ho hlakola, ho hlakola, ho qala tahlehelo ea codon, ho emisa ho lahleheloa ke liphatsa tsa lefutso, joalo-joalo. Phapang ea sebopeho ke tlhophiso e kholo ea genome, e kenyelletsang likarolo tsa liphatsa tsa lefutso ho tloha ho metheo e likete tse 'maloa ho isa ho bongata ba chromosome, ho kopanyelletsa le liphetoho tsa chromosome. phetohelo kapa phalliso. Liphetoho tsena li ka baka phokotso kapa ntlafatso ea ts'ebetso ea protheine. Ntle le liphetoho boemong ba liphatsa tsa lefutso ka bomong, li-signature tsa genomic le tsona ke karolo ea litlaleho tsa tatellano ea kliniki. Li-signature tsa genomic li ka bonoa e le lipaterone tse rarahaneng tsa mefuta e nyane le / kapa ea sebopeho, ho kenyeletsoa tumor mutation load (TMB), microsatellite instability (MSI), le liphoso tsa homologous recombination.

Phetoho ea Clonal le phetoho ea subclonal. Liphetoho tsa clonal li teng liseleng tsohle tsa hlahala, li teng ha ho hlahlojoa, 'me li lula li le teng ka mor'a tsoelo-pele ea phekolo. Ka hona, liphetoho tsa clonal li na le monyetla oa ho sebelisoa e le sepheo sa kalafo ea tumor. Liphetoho tsa subclonal li teng feela karolong e nyenyane ea lisele tsa kankere 'me li ka fumanoa qalong ea tlhahlobo, empa li nyamela ka ho pheta-pheta kapa ho hlaha feela ka mor'a phekolo. Cancer heterogeneity e bolela ho ba teng ha liphetoho tse ngata tsa subclonal mofetšeng o le mong. Haholo-holo, boholo ba liphetoho tse kholo tsa mofetše mefuteng eohle e tloaelehileng ea mofetše ke liphetoho tsa clonal 'me li lula li tsitsitse nakong eohle ea tsoelo-pele ea mofetše. Khanyetso, e atisang ho kopanngoa ke li-subclones, e ka 'na ea se ke ea fumanoa nakong ea ho hlahlojoa empa e hlaha ha e khutlela morao ka mor'a phekolo.

Mokhoa oa setso oa FISH kapa cell karyotype o sebelisoa ho bona liphetoho boemong ba chromosomal. FISH e ka sebelisoa ho lemoha ho kopanngoa ha liphatsa tsa lefutso, ho tlosoa, le ho holisoa, 'me e nkoa e le "tekanyetso ea khauta" bakeng sa ho lemoha mefuta e joalo, ka ho nepahala le kutloisiso e phahameng empa ho na le moeli o fokolang. Likarolong tse ling tsa malignancies, haholo-holo acute leukemia, karyotyping e ntse e sebelisoa ho tataisa tlhahlobo le prognoza, empa mokhoa ona butle-butle o nkeloa sebaka ke liteko tse lebisitsoeng tsa limolek'hule tse kang FISH, WGS, le NGS.
Liphetoho liphatseng tsa lefutso ka bomong li ka bonoa ke PCR, PCR ea nako ea nnete le PCR ea ho theoha ea dijithale. Mekhoa ena e na le kutlo e phahameng, ka ho khetheha e loketse ho lemoha le ho beha leihlo maqeba a manyenyane a setseng, 'me e ka fumana liphello ka nako e batlang e le khutšoanyane, bothata ke hore mefuta e mengata ea ho lemoha e lekanyelitsoe (hangata e lemoha feela liphetoho tsa lefutso le le leng kapa tse seng kae), le bokhoni ba ho etsa liteko tse ngata bo lekanyelitsoe.
Immunohistochemistry (IHC) ke sesebelisoa sa tlhahlobo se thehiloeng ho protheine se atisang ho sebelisoa ho bona polelo ea li-biomarker tse kang ERBB2 (HER2) le li-receptor tsa estrogen. IHC e ka boela ea sebelisoa ho bona liprotheine tse fetotsoeng (tse kang BRAF V600E) le mefuta e itseng ea liphatsa tsa lefutso (joaloka ALK fusions). Molemo oa IHC ke hore o ka kenngoa habonolo ts'ebetsong ea tlhahlobo ea lisele tse tloaelehileng, kahoo e ka kopanngoa le liteko tse ling. Ho feta moo, IHC e ka fana ka tlhahisoleseling mabapi le sebaka sa protheine ea subcellular. Mefokolo ke scalability e fokolang le litlhoko tse phahameng tsa mokhatlo.
Moloko oa bobeli oa tatellano (NGS) NGS e sebelisa mekhoa e phahameng ea ho tsamaisana ka mokhoa o ts'oanang ho lemoha ho fapana ha boemo ba DNA le / kapa RNA. Mokhoa ona o ka sebelisoa ho tatellana ka bobeli liphatsa tsa lefutso (WGS) le libaka tsa liphatsa tsa lefutso tse khahlang. WGS e fana ka tlhaiso-leseling e felletseng ea phetoho ea liphatsa tsa lefutso, empa ho na le litšitiso tse ngata ts'ebelisong ea eona ea bongaka, ho kenyeletsoa tlhoko ea lisampole tse ncha tsa lisele tsa tumor (WGS ha e so lokele ho sekaseka disampole tse sa sebetseng hantle) le litšenyehelo tse phahameng.
Tatellano e reriloeng ea NGS e kenyelletsa tatellano e felletseng ea exon le phanele ea liphatsa tsa lefutso. Liteko tsena li ntlafatsa libaka tse khahlang ka DNA probes kapa PCR amplification, ka tsela eo e fokotsa palo ea tatellano e hlokahalang (exome kaofela e etsa karolo ea 1 ho isa ho 2 lekholong ea genome, esita le liphanele tse kholo tse nang le liphatsa tsa lefutso tse 500 li etsa karolo ea 0.1 lekholong feela ea genome). Leha tatellano eohle ea exon e sebetsa hantle ka har'a lithane tse tsitsitseng tsa formalin, litšenyehelo tsa eona li lula li le holimo. Metsoako ea liphatsa tsa lefutso e batla e na le chelete e ngata 'me e lumella ho fetoha ha maemo ha ho khethoa liphatsa tsa lefutso tse lokelang ho lekoa. Ntle le moo, ho potoloha DNA ea mahala (cfDNA) ho hlaha e le khetho e ncha bakeng sa tlhahlobo ea genomic ea bakuli ba mofetše, e tsejoang ka hore ke li-biopsies tsa metsi. Ka bobeli lisele tsa mofetše le lisele tse tloaelehileng li ka lokolla DNA maling, 'me DNA e tšolotsoeng liseleng tsa mofetše e bitsoa circulating tumor DNA (ctDNA), e ka hlahlojoang ho bona liphetoho tse ka bang teng liseleng tsa hlahala.
Khetho ea tlhahlobo e itšetlehile ka bothata bo itseng ba kliniki bo lokelang ho rarolloa. Boholo ba li-biomarker tse amanang le liphekolo tse amohetsoeng li ka bonoa ka mekhoa ea FISH, IHC, le PCR. Mekhoa ena e utloahala bakeng sa ho lemoha li-biomarker tse nyenyane, empa ha li ntlafatse bokhoni ba ho lemoha ka ho eketseha ha lihlahisoa, 'me haeba li-biomarker tse ngata li fumanoa, ho ka' na ha se ke ha e-ba le lisele tse lekaneng bakeng sa ho fumanoa. Mefuteng e meng ea mofetše, joalo ka mofetše oa matšoafo, moo ho leng thata ho fumana lisampole tsa lisele, 'me ho na le li-biomarker tse ngata tse lokelang ho hlahlojoa, ho sebelisa NGS ke khetho e ntle. Qetellong, khetho ea tlhahlobo e itšetlehile ka palo ea li-biomarker tse lokelang ho lekoa bakeng sa mokuli e mong le e mong le palo ea bakuli ba lokelang ho hlahlojoa bakeng sa biomarker. Maemong a mang, tšebeliso ea IHC / FISH e lekane, haholo-holo ha sepheo se tsejoa, joalo ka ho fumanoa ha li-receptor tsa estrogen, li-receptor tsa progesterone, le ERBB2 ho bakuli ba kankere ea matsoele. Haeba ho hlokahala tlhahlobo e felletseng ea liphetoho tsa genomic le ho batla sepheo sa kalafo se ka bang teng, NGS e hlophisehile haholoanyane ebile e na le litšenyehelo tse ngata. Ho feta moo, NGS e ka nahanoa maemong ao liphetho tsa IHC/FISH li sa hlakang kapa li sa fihlelleng hantle.

Litaelo tse fapaneng li fana ka tataiso ea hore na bakuli ba lokela ho tšoaneleha bakeng sa tlhahlobo ea lefutso. Ka 2020, ESMO Precision Medicine Working Group e ile ea fana ka litlhahiso tsa pele tsa tlhahlobo ea NGS bakeng sa bakuli ba nang le mofetše o tsoetseng pele, e khothaletsa tlhahlobo ea kamehla ea NGS bakeng sa mofetše oa matšoafo o seng oa squamous o seng o monyane oa lisele tsa matšoafo, mofets'e oa senya, mofets'e oa colorectal, mofets'e oa mofets'e le lisampole tsa mofets'e oa mahe a bomme, mme ka 2024, ESMO e ile ea nchafatsoa motheong ona oa mofetše oa matsoele. Joalo ka lihlahala tsa stromal tsa ka mpeng, li-sarcomas, mofets'e oa qoqotho le mofets'e o sa tsejoeng.
Ka 2022, ASCO's Clinical Opinion mabapi le tlhahlobo ea genome ea somatic ho bakuli ba nang le mofetše oa metastatic kapa o tsoetseng pele o re haeba kalafo e amanang le biomarker e amoheloa ho bakuli ba nang le metastatic kapa li-tumor tse tiileng tse tsoetseng pele, tlhahlobo ea liphatsa tsa lefutso e khothaletsoa ho bakuli bana. Mohlala, tlhahlobo ea genomic e lokela ho etsoa ho bakuli ba nang le melanoma ea metastatic ho hlahloba liphetoho tsa BRAF V600E, kaha li-inhibitors tsa RAF le MEK li lumelletsoe pontšo ena. Ho phaella moo, tlhahlobo ea liphatsa tsa lefutso e boetse e lokela ho etsoa haeba ho na le letšoao le hlakileng la ho hanyetsa hore moriana o fuoe mokuli. Mohlala, Egfrmab, ha e sebetse ho mofetše oa mala oa KRAS o fetohang. Ha ho nahanoa ka ho tšoaneleha ha mokuli bakeng sa tatellano ea liphatsa tsa lefutso, boemo ba 'mele oa mokuli, li-comorbidities, le sethala sa tumor se lokela ho kopanngoa, hobane letoto la mehato e hlokahalang bakeng sa tatellano ea liphatsa tsa lefutso, ho kenyelletsa le tumello ea mokuli, ts'ebetso ea laboratori, le tlhahlobo ea liphetho tsa tatellano, li hloka hore mokuli a be le matla a lekaneng a' mele le tebello ea bophelo.
Ntle le liphetoho tsa somatic, mefuta e meng ea mofetše le eona e lokela ho hlahlojoa bakeng sa liphatsa tsa lefutso. Teko ea liphetoho tsa methapo ea likokoana-hloko e ka ama liqeto tsa kalafo bakeng sa mofetše o kang BRCA1 le BRCA2 liphetoho tsa matsoele, mahe a bomme, tšoelesa ea senya le manyeme. Liphetoho tsa likokoana-hloko li ka 'na tsa e-ba le liphello bakeng sa ho hlahloba le ho thibela kankere nakong e tlang ho bakuli. Bakuli ba ka 'nang ba tšoaneleha bakeng sa tlhahlobo ea liphetoho tsa likokoana-hloko ba hloka ho finyella maemo a itseng, a kenyelletsang lintlha tse kang histori ea lelapa la mofetše, lilemo tsa tlhahlobo, le mofuta oa mofetše. Leha ho le joalo, bakuli ba bangata (ho fihlela ho 50%) ba jereng liphetoho tsa pathogenic moleng oa kokoana-hloko ha ba finyelle mekhoa ea setso bakeng sa tlhahlobo ea liphetoho tsa likokoana-hloko ho latela histori ea lelapa. Ka hona, ho eketsa boitsebahatso ba bajari ba liphatsa tsa lefutso, National Comprehensive Cancer Network (NCCN) e khothaletsa hore bakuli bohle kapa bongata ba bakuli ba nang le mofetše oa matsoele, mahe a bomme, endometrial, pancreatic, colorectal, kapa prostate ba lekoe bakeng sa liphetoho tsa mela ea likokoana-hloko.
Mabapi le nako ea tlhahlobo ea liphatsa tsa lefutso, hobane boholo ba liphetoho tse kholo tsa mokhanni ke tsa clonal 'me li batla li tsitsitse nakong ea tsoelo-pele ea mofetše, hoa utloahala ho etsa tlhahlobo ea liphatsa tsa lefutso ho bakuli nakong ea tlhahlobo ea mofetše o tsoetseng pele. Bakeng sa tlhahlobo e latelang ea liphatsa tsa lefutso, haholo-holo ka mor'a phekolo e lebisitsoeng ho limolek'hule, tlhahlobo ea ctDNA e molemo ho feta DNA ea lisele tsa hlahala, hobane DNA ea mali e ka ba le DNA ho tsoa maqeba 'ohle a hlahala, e leng ntho e loketseng ho fumana tlhahisoleseding e mabapi le tumor heterogeneity.
Tlhahlobo ea ctDNA kamora kalafo e ka khona ho bolela esale pele karabelo ea hlahala kalafong le ho tseba tsoelo-pele ea lefu pele ho mekhoa e tloaelehileng ea ho nka litšoantšo. Leha ho le joalo, liprothokholo tsa ho sebelisa lintlha tsena ho tataisa liqeto tsa kalafo ha li so thehoe, 'me tlhahlobo ea ctDNA ha e khothalletsoe ntle le litekong tsa bongaka. ctDNA e ka boela ea sebelisoa ho lekola maqeba a manyane a setseng ka mor'a opereishene e matla ea hlahala. Tlhahlobo ea ctDNA ka mor'a ho buuoa ke sesupo se matla sa tsoelo-pele ea lefu le latelang 'me e ka thusa ho tseba hore na mokuli o tla rua molemo ho chemotherapy ea adjuvant, empa ho ntse ho sa khothaletsoe ho sebelisa ctDNA ka ntle ho liteko tsa meriana ho tataisa liqeto tsa adjuvant chemotherapy.

Ts'ebetso ea data Mohato oa pele oa tatellano ea liphatsa tsa lefutso ke ho ntša DNA ho lisampole tsa bakuli, ho lokisa lilaeborari, le ho hlahisa datha ea tatelano e tala. Lintlha tse tala li hloka ts'ebetso e eketsehileng, ho kenyelletsa le ho sefa data ea boleng bo tlase, ho e bapisa le genome ea referense, ho tsebahatsa mefuta e fapaneng ea liphetoho ka li-algorithms tse fapaneng tsa tlhahlobo, ho fumana phello ea liphetoho tsena phetolelong ea protheine, le ho sefa liphetoho tsa mela ea likokoana-hloko.
Tlhaloso ea liphatsa tsa lefutso tsa mokhanni e etselitsoe ho khetholla liphetoho tsa mokhanni le bapalami. Liphetoho tsa mokhanni li lebisa tahlehelong kapa ntlafatsong ea ts'ebetso ea liphatsa tsa lefutso tsa tumor suppressor. Mefuta e menyane e lebisang ho ts'ebetsong ha liphatsa tsa lefutso tsa tumor suppressor li kenyelletsa liphetoho tse se nang kelello, liphetoho tsa li-frameshift, le liphetoho tsa mantlha tsa sebaka sa marang-rang, hammoho le ho hlakoloa ha li-codon khafetsa, ho hlakoloa ha codon, le mefuta e mengata e fapaneng ea ho kenya / ho hlakola. Ntle le moo, liphetoho tse mpe le liphetoho tse nyane tsa ho kenya / ho hlakola li ka lebisa tahlehelong ea ts'ebetso ea liphatsa tsa lefutso tsa tumor suppressor ha e ama libaka tsa bohlokoa tse sebetsang. Mefuta e fapaneng ea sebopeho e lebisang tahlehelong ea ts'ebetso ea liphatsa tsa lefutso tsa tumor suppressor e kenyelletsa ho hlakoloa ha liphatsa tsa lefutso ka mokhoa o sa fellang kapa ka botlalo le mefuta e meng ea genomic e lebisang timetsong ea foreimi ea ho bala. Liphetoho tse nyane tse lebisang ts'ebetsong e ntlafetseng ea li-oncogenes li kenyelletsa liphetoho tsa missense le ho kenngoa / ho tlosoa ha intron ka linako tse ling tse lebisang libakeng tsa bohlokoa tsa ts'ebetso ea protheine. Maemong a sa tloaelehang, ho fokotseha ha protheine kapa liphetoho tsa sebaka sa splicing ho ka lebisa ts'ebetsong ea li-oncogenes. Phapang ea sebopeho e lebisang ts'ebetsong ea oncogene e kenyelletsa fusion ea liphatsa tsa lefutso, ho hlakoloa ha liphatsa tsa lefutso, le phetiso ea liphatsa tsa lefutso.
Tlhaloso ea bongaka ea phetoho ea genomic e lekola bohlokoa ba liphatsa tsa lefutso tse khethiloeng, ke hore, boleng ba tsona ba ho hlahloba, ho tsebahatsa pele kapa kalafo. Ho na le litsamaiso tse 'maloa tse thehiloeng bopaking tse ka sebelisoang ho tataisa tlhaloso ea bongaka ea phapang ea genomic.
Setsi sa Memorial Sloan-Kettering Cancer Center's Precision Medicine Oncology Database (OncoKB) se arola mefuta e fapaneng ea liphatsa tsa lefutso ka mekhahlelo e mene ho latela boleng ba bona bo boletsoeng esale pele bakeng sa tšebeliso ea lithethefatsi: Level 1/2, FDA-approved, kapa clinical-standard biomarkers tse bolelang esale pele karabelo ea pontšo e itseng ho sethethefatsi se amohelehang; Boemo ba 3, li-biomarker tse amohetsoeng ke FDA kapa tse sa amoheloeng tse bolelang esale pele karabelo ho litlhare tse lebisitsoeng tse ncha tse bonts'itseng ts'episo litekong tsa bongaka, le Level 4, li-biomarker tse sa lumelloeng ke FDA tse bolelang esale pele karabelo ho litlhare tse lebisitsoeng tse ncha tse bonts'itseng bopaki bo kholisang ba tlhaho litekong tsa bongaka. Sehlotšoana sa bohlano se amanang le ho hanyetsa kalafo se ile sa eketsoa.
Mokhatlo oa Amerika oa Molecular Pathology (AMP)/American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) tataiso bakeng sa tlhaloso ea phapang ea somatic e arola phapang ea somatic ka mekhahlelo e mene: Sehlopha sa I, se nang le bohlokoa bo matla ba kliniki; Sehlopha sa II, se nang le bohlokoa ba kliniki; Sehlopha sa III, bohlokoa ba kliniki bo sa tsejoe; Sehlopha sa IV, se sa tsejoeng se le bohlokoa ho tsa bongaka. Ke mefuta ea sehlopha sa I le II feela tse bohlokoa bakeng sa liqeto tsa kalafo.
ESMO's Molecular Target Clinical Operability Scale (ESCAT) e arola mefuta e fapaneng ea liphatsa tsa lefutso ka mekhahlelo e tšeletseng: Level I, lipehelo tse loketseng tšebeliso ea kamehla; Mokhahlelo oa II, sepheo se ntseng se ithutoa, ho ka etsahala hore se sebelisoe ho hlahloba palo ea bakuli ba ka ruang molemo ho sethethefatsi se lebisitsoeng, empa ho hlokahala lintlha tse ngata ho e tšehetsa. Sehlopha sa III, mefuta e fapaneng ea liphatsa tsa lefutso e bonts'itseng molemo oa bongaka mefuteng e meng ea mofetše; Mophato oa IV, ke mefuta e fapaneng ea liphatsa tsa lefutso e lebisitsoeng feela e tšehetsoeng ke bopaki ba preclinical; Sehlopheng sa V, ho na le bopaki bo tšehetsang bohlokoa ba kliniki ba ho lebisa tlhokomelo phetohong, empa phekolo ea meriana e le 'ngoe khahlanong le sepheo ha e atolose ho phela, kapa leano la phekolo le kopantsoeng le ka amoheloa; Sehlopha sa X, ho hloka boleng ba bongaka.