Zvekuita nezvekuramba zvinodhaka kweasiri-diki kenza yemapapu yakanangana nemishonga, unoda kuziva pano
Lung cancer is the cancer with the highest morbidity and mortality in China. About 1.6 million people die of this disease each year worldwide, and about 85% of these cases are non-small cell lung cancer (NSCLC). At present, many cancer-targeting drugs have been developed for advanced isina-diki kenza yemapapu kenza in the world. These new therapeutic drugs have increased the median survival time of patients to 35 months, which not only significantly prolonged their life span, but also achieved Personalized treatment. However, most patients will develop secondary drug resistance 8 to 14 months after receiving EGFR-TKI (standard first-line treatment for patients with sensitive mutations in the EGFR gene). How to solve the problem of drug resistance has become a hot research topic. Will continue to answer for everyone.
1. Nei yakanangidzirwa kurapwa kweasina-madiki maseru emukenza mapapu anodzivirira?
Kusvitswa kwezvinodhaka zvinodhaka kunowanzo kuve kwakakamurwa kuita kwekutanga kuramba uye kwechipiri kuramba.
1. Mushonga wekutanga wemishonga: zvinoreva murwere iyeye EGFR chinangwa chinoshanduka, asi nekuda kwekuvapo kwechisikirwo kweKRAS geni shanduko, gefitinib uye erlotinib hydrochloride mapiritsi uye mimwe mishonga yakanangwa haishande, Mushure memwedzi mitatu yekushandisa, kuramba kwemishonga kunoitika.
2. Sekondari kusagadzikana kwezvinodhaka: In the course of targeted drug treatment, because the target signal pathway continues to be inhibited by drugs, the tumarara produces other gene mutations in order to escape the drug, inhibiting the therapeutic effect of the targeted drug on the EGFR target, thereby Lead to drug resistance. The effective time of medication is usually more than 3 months.
2. Mishonga inodzivirira nzira yekurapa kwakanangwa kweasina-madiki kenza yemapapu kenza
There are currently three specific mechanisms for non-small cell kenza yemapapu drug resistance. First, drug resistance is generated through genetic mutation. About 40% of the genes in patients with positive genetic tests will generate new genes from the original genes, which will cause insensitivity to the original drugs, resulting in drug resistance. Secondly, the cunning cancer cells will usually “repair the dark path of the plank road” and take a detour. This situation accounts for about 20% of patients with drug resistance. In addition to the above two drug resistance pathways, the drug resistance mechanism of the remaining 30% of patients is not yet clear.
3. Maitiro ekutonga kuti varwere vane isina-diki maseru kenza yemapapu vane kusagadzikana kwemishonga?
1. Kazhinji, kana mushonga wacho usingamiri, mushonga wakanangwa haugoni kudzora kukura kwebundu, izvo zvichaita kuti bundu racho rikure kana kuti rikure kure. Panguva ino, murwere anenge aine zvimwe zviratidzo, sekunge asina kukosora kare, asi achangotanga kukosora, kana mushure memetastasis yehuropi Murwere achange aine dzungu, musoro, kurutsa pasina chikonzero, uye varwere vane metastasis yebhonzo vanonzwa kurwadziwa, kudzvanywa kwetsinga uye zvimwe zviratidzo. Panguva ino, murwere anofanira kunge akangwarira.
2. Kune varwere vanogona kukura kusagadzikana nemushonga, nzira yakanakisa ndeyekuenda kuchipatara kunoongororwazve. Sarudza kana chakanangwa chinodzvinyirira nemushonga mamakisi uye kuongorora kwekufungidzira.
4. Mushure mekunge murwere atanga kusagadzikana nemushonga, chiremba anowanzo kurudzira bhiopsy yechipiri, zvinorevei
Kazhinji kutaura, vese varwere vane kenza yemapapu vanotora EGFR-TRI madhiragi uye vane chirwere chekufambira mberi vanofanirwa kuenda kechipiri biopsy.
1. Bvisa hutachiona hwehutachiona zvakare kuti uone kana iri kenza nyowani yekutanga kana gomarara rinodzokororwa.
2. Ita bvunzo yechipiri yemajini kuti uone kana iko kuramba kwemishonga kunokonzerwa nekushanduka kwejini zvakare, uye kuona kana paine chirongwa chitsva chekurapa chakanangana.
Yechipiri biopsy inogona kuona nekukasira kufambira mberi kwechirwere, kuratidza nzira dzekuramba zvinodhaka, uye kugadzira zvirongwa zvekurapa zvekutevera. Yechipiri biopsy inonyanya kukamurwa kuita tishu biopsy uye liquid biopsy. Tissue biopsy inonyanya kukamurwa kuita thoracotomy biopsy, bronchoscopy biopsy uye percutaneous lung biopsy. Kune varwere vasingakwanise kuwana tumor tissue, liquid biopsy yakavakirwa paropa NGS gene sequencing tekinoroji inogona kusarudzwa kuti iwane mimwe mikana yekurapa.
5. Chii chandinofanira kuita kana kushomeka kwemishonga kuchionekwa mushure meyekutanga-chizvarwa TKI yakanangwa kurapwa kweasina-madiki maseru kenza yemapapu?
Chizvarwa chekutanga cheEGFR-TKI chinosanganisira gefitinib, erlotinib, uye icotinib.
Sekureva kwenhungamiro dzeNCCN, T790M shanduko yekuyedza inotanga kukurudzirwa mushure mekutanga chizvarwa cheEGFR-TKI kuramba. Maitiro akasiyana anotorwa zvinoenderana nekuti murwere ane zviratidzo here, kungave kune metastasis yeuropi, kungave kufambira mberi kwenzvimbo kana kuwanda kwakawanda.
1. Kune varwere vane T790M yakanaka: iyo kurudziro yekutanga ndeyeOsimertinib kurapwa, ramba uchirapa TKI kune varwere vanononoka kufambira mberi, uye kurapwa kwenzvimbo kune varwere vane kufambira mberi kwenzvimbo, kusanganisira radiotherapy yebrain metastasis, radiotherapy yemunharaunda kune imwechete lesion Kutora chemotherapy kune varwere vane kufambira mberi kwakanyanya.
2. Kune T790M-isina varwere: chemotherapy inogona kupihwa, kana immunotherapy may be selected based on the PD-L1 expression of the patient.
3. Kune varwere vane asymptomatic mushure mekurwisa zvinodhaka: kurapwa kwemunharaunda kunogona kutorwa kana kuenderera kwechizvarwa chekurapa kweTKI. Kune varwere vane chete huro metastases, kurapwa kwemuno kunogona kutariswa, uye kuramba uchishandisa chizvarwa chekutanga cheEGFR-TKI.
6. Inguva yakareba sei mushure mekutora osimertinib inokudziridza kuramba kwemishonga?
Osimertinib ndiyo yechitatu-chizvarwa EGFR-TKI yakanangwa mishonga ine avhareji yekurwisa zvinodhaka nguva ingangoita gumi nemana mwedzi. Zvisinei, mumakiriniki ekushandisa, varwere vazhinji vanoitawo kushanduka kwekudzivirira mushure memakore maviri kana matatu mushure mekutora osimertinib, saka Iyo yakatarwa mamiriro e oxitinib yekudzivirira nguva inosiyana kubva pamunhu kuenda kumunhu.
7. Ndeipi nzira yekurwisa mishonga yeosimertinib?
Iyo yekudzivirira mushonga mashandiro eosimertinib yakaoma kwazvo, kusanganisira C797S mutation, MET amplification / RET rearrangement / ROS-1 rearrangement, HER-2 kukurudzira, BRAF mutation, RAS mutation, FGFR1 mutation, kutendeuka kune diki cell cancer kenza, Iko hakuna majini shanduko, nezvimwewo, uye anotevera madhiragi emushonga emhando dzakasiyana dzekurwisa zvinodhaka akasiyana.
1. EGFR geni shanduko zvakare: EGFR796 uye 797 shanduko dzaive ne24.7%, EGFR 792 shanduko dzaive ne10.8%, EGFR 718 uye 719 shanduko dzaive ne9.7% -EGFR gene, shanduka-isingachinjiki, kuverenga kwe45% yevarwere vese, padyo nehafu yenyika.
2. Dzimwe shanduko dzegene: kusanganisira PIK3CA, BRAF, MET, RET, KRAS, nezvimwewo Zvakawanda zvakajairika uye zvisingawanzoitika gomarara remukenza remapapu majini anobatanidzwa uye akapararira.
3. Akashandurwa kuita kenza diki yemukenza yemapapu.
8. Chii chekuita mushure meOxitinib yakanangwa kurapwa kwekurwisa zvinodhaka?
Kune akasiyana majini ekurwisa, mhinduro yekutanga ndeinotevera:
1. Nezvenyaya yekuchinja katatu (C797S / T790M / 19-del), mhedzisiro yekusarudza bugatinib iri nani pane osimertinib / gefitinib, uye mhedzisiro haina kukanganiswa nenzvimbo yenzvimbo yeC797S uye T790M. (1) Bugatinib yakasanganiswa neye-anti-EGFR kirasi (cetuximab / panitumumab) inogona kusimudzira kurapa kwehutatu hwekuchinja, uye kusanganiswa kwemishonga miviri kunogona kuridza mushandira pamwe. (2) Bugatinib inosanganiswa naSelumetinib (Simetinib) inogona kukunda kurwisa kweosimertinib kunokonzerwa neC797S mutation.
2. Nezve trans-kurongeka kweEGFR C797S, funga yekutanga-chizvarwa chakanangwa mishonga inosanganiswa neyechitatu-chizvarwa chakanangwa zvinodhaka, senge osimertinib inosanganiswa ne gefitinib / erlotinib. Kune iyo cis-kuenderana, iwe unogona
sarudza Bugatinib + VEGF yakanangwa zvinodhaka.
3. Kana paine chete C79CS mutation, unogona kushandisa chizvarwa chekutanga EGFR inhibitor, senge gefitinib, erlotinib, icotinib.
4. MET amplification inoratidza kuti osimertinib inosanganiswa neMET inhibitors (camatinib, crizotinib, Savolitinib, nezvimwewo). BRAF shanduko dzinoratidza kuti osimertinib inosanganiswa neBRAF inhibitors (dalafinib + trametinib). RET mutation yakaratidza kuti Osimertinib inosanganiswa neKotinib, uyezve zvirinani Osimertinib inosanganiswa neBUU-667.
Zvinokurudzirwa kuti mushure mekushorwa kwe oxetinib, zviri nani kuita genetiyamu zvakare, uye sarudza chakakodzera chakanangwa mushonga zvichienderana nechinangwa chekuchinja kuti ubatsire kurapwa zvakanaka. Zvakanakisisa kubvunza chiremba ane hunyanzvi nezvekubatanidza kurapa kwemishonga yakanangwa.
9. Mhedzisiro mhedzisiro yekenza isiri-diki yemukenza yemapapu yakanangwa nemishonga
Chinangwa chemakemikari akanangana nemishonga akajeka, asi hazvireve kuti hapana kiriniki yakashata inoitika ichaitika. Maitiro akashata emishonga yakanangwa senge manyoka, proteinuria, kukwirisa kweropa, acne-kunge mapundu uye chirwere chemwoyo zvinozivikanwa. Kunyangwe zvakanangwa zvinodhaka zvakaderera pane zvechinyakare cytotoxic zvinodhaka, hazvisati zvichizofanirwa kutarisirwa pasi. Kumwe kuita kusingawanzo kuve kwakanyanya kunowanzo kunetsa kuongororwa nekuda kwekuongororwa kwechipatara, kazhinji zvichitungamira kumhedzisiro.
Semuenzaniso, erlotinib kurapwa kunogona kukonzera asymptomatic chiropa transaminase kukwirira, uye kubuda kwematumbo kubuda ropa hakuwanzo kutaurwa, nepo gefitinib idiki mamorekuru inorwisa-EGFR yakanangwa kurapwa, kunyange metabolism yayo iri kunyanya chiropa Inenge 4% inojekeswa neitsvo muchimiro cheprototypes uye metabolites, uye kiriniki inokonzeresa kukundikana kweitsvo kwakanyanya, izvo zvinovandudza mushure mekusiya zvinodhaka. Mukurapwa kwezvinodhaka, zvakakomba uye zvinouraya maitiro akashata anofanirwa kudzivirirwa zvakanyanya. Maitiro akashata anochinja chivimbo chemurwere pakurapwa. Kuita kwakakomba kwakashata kunogona kukanganisa maitiro ekurapa.
