What to do about drug resistance of non-small cell lung cancer targeted drugs, you want to know here
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 cututtukan daji na kansa marasa kansar 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. Me yasa maganin da ba ƙaramin ƙwayar huhu ba ke da juriya?
Juriya na miyagun ƙwayoyi yawanci ana raba shi zuwa juriya na farko da juriya na sakandare.
1. Maganin juriya na farko: yana nufin maye gurbi na maƙasudin EGFR na mai haƙuri, amma saboda kasancewar yanayin halittar halittar KRAS, allunan gefitinib da erlotinib hydrochloride da sauran magungunan da aka yi niyya ba su da tasiri , Bayan watanni 3 na amfani, juriya na miyagun ƙwayoyi yana faruwa.
2. Maganin juriya na biyu: In the course of targeted drug treatment, because the target signal pathway continues to be inhibited by drugs, the tumo 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. Tsarin juriya na miyagun ƙwayoyi na maganin da aka yi niyya don ciwon daji na huhu mara ƙananan ƙwayoyin cuta
There are currently three specific mechanisms for non-small cell kwayar cutar huhu 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. Yaya za a yi hukunci ko marasa lafiya da ciwon huhu marasa ƙananan ƙwayoyin cuta suna da juriya na ƙwayoyi?
1. Usually, when the drug is resistant, the targeted drug cannot control the growth of the tumor, which will cause the tumor to grow or metastasize far away. At this time, the patient will have certain symptoms, such as no cough before, but recently started coughing, or after brain metastasis The patient will have dizziness, headache, vomiting without cause, and patients with bone metastasis will experience pain, nerve compression and other symptoms. At this time, the patient needs to be vigilant.
2. Ga marasa lafiya waɗanda zasu iya haɓaka juriya na miyagun ƙwayoyi, hanya mafi kyau ita ce zuwa asibiti don dubawa akai-akai. Ƙayyade ko maganin da aka yi niyya yana da juriya ta alamomin ƙari da gwajin hoto.
4. Bayan mai haƙuri ya haɓaka juriya na miyagun ƙwayoyi, likita yakan ba da shawarar biopsy na biyu, menene ma'anarsa
Gabaɗaya magana, duk marasa lafiya da ke fama da ciwon huhu waɗanda ke shan magungunan EGFR-TRI kuma suna da ci gaban cuta ya kamata a yi biopsy na biyu.
1. Share ganewar asali don sanin ko sabon ciwon daji ne na farko ko kuma ciwon daji.
2. Carry out the second genetic test to determine whether it is drug resistance caused by the mutation of the gene again, and detect whether there is a new targeted treatment plan.
The second biopsy can promptly detect disease progression, reveal drug resistance mechanisms, and formulate appropriate follow-up treatment plans. The second biopsy is mainly divided into tissue biopsy and liquid biopsy. Tissue biopsy is mainly divided into thoracotomy biopsy, bronchoscopy biopsy and percutaneous lung biopsy. For patients who cannot obtain tumor tissue, liquid biopsy based on blood NGS gene sequencing technology can be selected to obtain further treatment opportunities.
5. Menene ya kamata in yi idan juriya na miyagun ƙwayoyi ya bayyana bayan ƙarni na farko na TKI da aka yi niyya na ciwon huhu na huhu mara ƙarami?
Farkon ƙarni na EGFR-TKI ya haɗa da gefitinib, erlotinib, da icotinib.
Dangane da jagororin NCCN, gwajin maye gurbin T790M an fara ba da shawarar bayan ƙarni na farko na juriya na EGFR-TKI. Ana ɗaukar dabaru daban-daban bisa ga ko mai haƙuri yana da alamun bayyanar, ko akwai metastasis na kwakwalwa, ko ci gaban gida ko ci gaba da yawa.
1. Ga marasa lafiya tare da tabbatacce T790M: da first recommendation is Osimertinib treatment, continue TKI treatment for patients with slow progression, and local treatment for patients with local progression, including radiotherapy for brain metastasis, local radiotherapy for single lesion To take chemotherapy for patients with extensive progress.
2. Ga marasa lafiya T790M: ana iya ba da chemotherapy, ko immunotherapy may be selected based on the PD-L1 expression of the patient.
3. Ga marasa lafiya waɗanda suke asymptomatic bayan juriya na miyagun ƙwayoyi: Ana iya ɗaukar ko ci gaba da jiyya na gida don tsararrun jiyya na TKI. Ga marasa lafiya tare da ƙananan ƙwayoyin kwakwalwa kawai, ana iya la'akari da jiyya na gida, kuma a ci gaba da amfani da ƙarni na farko na EGFR-TKI.
6. Yaya tsawon lokacin shan osimertinib zai haɓaka juriya na miyagun ƙwayoyi?
Osimertinib shine magani na ƙarni na uku na EGFR-TKI da aka yi niyya tare da matsakaicin lokacin juriyar ƙwayoyi na kusan watanni 11. Duk da haka, a cikin aikace-aikacen asibiti, marasa lafiya da yawa kuma suna haɓaka juriya bayan shekaru biyu ko uku bayan shan osimertinib, don haka takamaiman halin da ake ciki na lokacin juriya na oxitinib ya bambanta daga mutum zuwa mutum.
7. Menene tsarin juriya na miyagun ƙwayoyi na osimertinib?
Tsarin juriya na miyagun ƙwayoyi na osimertinib yana da rikitarwa sosai, gami da maye gurbin C797S, haɓaka MET / sake tsarawa RET / sake tsara ROS-1, haɓaka HER-2, maye gurbi na BRAF, maye gurbin RAS, maye gurbin FGFR1, canzawa zuwa ƙananan ƙwayoyin huhu na huhu, Babu kwayoyin halitta maye gurbi, da sauransu, da kuma tsarin magunguna na gaba don hanyoyin juriya na magunguna daban-daban sun bambanta.
1. EGFR maye gurbi kuma: EGFR796 da 797 maye gurbi sun kai kashi 24.7%, EGFR 792 maye gurbi sun kai kashi 10.8%, EGFR 718 da 719 maye gurbi sun hada da 9.7% -EGFR gene, maye gurbi mai juriya, lissafin kashi 45% na duk marasa lafiya, kusa da rabin kasar.
2. Sauran maye gurbi: ciki har da PIK3CA, BRAF, MET, RET, KRAS, da dai sauransu. Daban-daban iri-iri na gama-gari da ba a saba gani ba.
3. An canza shi zuwa ƙananan ƙwayar huhu.
8. Menene za a yi bayan Oxitinib da aka yi niyya don juriya na miyagun ƙwayoyi?
Ga kwayoyin juriya daban-daban, maganin farko shine kamar haka:
1. Don yanayin maye gurbi sau uku (C797S / T790M / 19-del), tasirin zaɓin bugatinib ya fi osimertinib / gefitinib, kuma tasirin sararin samaniya bai shafi C797S da T790M ba. (1) Bugatinib hade tare da anti-EGFR aji (cetuximab / panitumumab) na iya haɓaka tasirin warkewa na maye gurbi sau uku, kuma haɗuwa da kwayoyi biyu na iya yin tasirin daidaitawa; (2) Bugatinib haɗe tare da Selumetinib (Simetinib) na iya shawo kan juriyar osimertinib da ke haifar da maye gurbin C797S.
2. Domin trans-tsari na EGFR C797S, yi la'akari da ƙarni na farko da aka yi niyya magunguna hade da ƙarni na uku da ake nufi da kwayoyi, irin su osimertinib hade da gefitinib / erlotinib. Don cis-alignment, za ku iya
zaɓi magungunan Bugatinib + VEGF da aka yi niyya.
3. Idan akwai maye gurbin C79CS kawai, zaka iya amfani da mai hana EGFR na farko, irin su gefitinib, erlotinib, icotinib.
4. Ƙwararren MET yana nuna cewa osimertinib tare da masu hana MET (camatinib, crizotinib, Savolitinib, da dai sauransu). Maye gurbin BRAF yana ba da shawarar cewa osimertinib hade da masu hana BRAF (dalafinib + trametinib). Maye gurbin RET ya ba da shawarar cewa Osimertinib ya haɗu da Kabotinib, kuma ba shakka mafi kyau shine Osimertinib hade da BLU-667.
Ana ba da shawarar cewa bayan juriya na oxetinib, yana da kyau a sake yin gwajin kwayoyin halitta, kuma a zaɓi maganin da aka yi niyya da ya dace bisa ga maƙasudin maye gurbi don ƙarin taimako na jiyya. Zai fi kyau a tuntuɓi ƙwararren likita don haɗuwa da magungunan da aka yi niyya.
9. Abubuwan da ke haifar da cutar kansar huhun da ba ƙananan ƙwayoyin cuta ba
Manufar magungunan kwayoyin da aka yi niyya a bayyane yake, amma ba yana nufin cewa babu wani mummunan halayen asibiti da zai faru ba. Mummunan halayen magungunan da aka yi niyya kamar su gudawa, proteinuria, hawan jini, kuraje-kamar kurji da cututtukan zuciya sananne ne. Kodayake magungunan da aka yi niyya sun yi ƙasa da magungunan cytotoxic na gargajiya, har yanzu ba za a yi la'akari da su ba. Wasu halayen da ba kasafai suke faruwa ba sau da yawa suna da wahalar ganowa saboda ganewar asibiti, galibi suna haifar da mummunan sakamako.
Misali, maganin erlotinib na iya haifar da hawan asymptomatic hanta transaminase, kuma ba kasafai ake ba da rahoton zubar jini na gastrointestinal ba, yayin da gefitinib karamin kwayar cutar anti-EGFR ne wanda aka yi niyya, kodayake metabolism ya fi hanta Kusan 4% ana sharewa ta hanyar kodan ta hanyar samfuri. da metabolites, da kuma asibiti mai saurin kamuwa da gazawar koda, wanda ke inganta bayan cirewar miyagun ƙwayoyi. A cikin maganin miyagun ƙwayoyi da aka yi niyya, ya kamata a guje wa mummunan halayen haɗari har ma da mutuwa gwargwadon yiwuwa. Abubuwan da ba su da kyau za su yi tasiri ga amincewar mai haƙuri a cikin jiyya. Mummunan halayen haɗari na iya katse tsarin jiyya.
