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 kanker paru sél non-leutik 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. Naha terapi anu ditargetkeun pikeun kanker paru-paru sél leutik tahan?
Résistansi ubar anu sasaran biasana dibagi kana résistansi primér sareng résistansi sékundér.
1. résistansi ubar primér: ngarujuk kana mutasi target EGFR pasién nyalira, tapi kusabab ayana alami mutasi gén KRAS, gefitinib sareng tablet hidroklorida erlotinib sareng ubar target sanés henteu épéktip, Saatos 3 sasih panggunaan, résistansi ubar lumangsung.
2. résistansi ubar sekundér: In the course of targeted drug treatment, because the target signal pathway continues to be inhibited by drugs, the tumor 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. Mékanisme tahan ubar tina targét anu ditujukeun pikeun kanker paru-paru sél leutik
There are currently three specific mechanisms for non-small cell kanker paru 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. Kumaha carana nangtoskeun naha pasién kanker paru-paru sél sanés alit gaduh résistansi ubar?
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. Pikeun pasién anu tiasa ngembangkeun résistansi ubar, cara anu pangsaéna nyaéta angkat ka rumah sakit kanggo marios rutin. Nangtukeun naha ubar anu ditujukeun tahan ku spidol tumor sareng pamariksaan imaging.
4. Saatos pasién ngembangkeun résistansi ubar, dokter biasana nyarankeun biopsi kadua, naon maksadna
Sacara umum, sadaya pasién kanker paru anu nginum obat EGFR-TRI sareng ngalaman panyakit kedah ngalaman biopsi kadua.
1. Mupus diagnosis patologis deui pikeun nangtoskeun naha éta mangrupikeun kanker primér anyar atanapi kambuh kanker.
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. Naon anu kuring kedah lakukeun upami résistansi ubar némbongan saatos TKI generasi kahiji sasaran terapi kanker paru-paru sél leutik?
Generasi kahiji EGFR-TKI kalebet gefitinib, erlotinib, sareng icotinib.
Numutkeun kana pedoman NCCN, uji coba mutasi T790M munggaran disarankeun saatos generasi kahiji résistansi EGFR-TKI. Strategi anu béda diadopsi numutkeun naha pasién ngagaduhan gejala, naha aya metastasis otak, naha kamajuan lokal atanapi sababaraha kamajuan.
1. Pikeun pasién anu positip T790M: anu 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. Pikeun penderita T790M-négatip: kémoterapi bisa dibikeun, atawa immunotherapy may be selected based on the PD-L1 expression of the patient.
3. Pikeun pasién anu asimtomatik saatos tahan ubar: perlakuan lokal tiasa dilaksanakeun atanapi diteraskeun pikeun generasi perlakuan TKI. Pikeun penderita ngan ukur metastasis uteuk, pangobatan lokal tiasa dianggap, sareng teras nganggo generasi kahiji EGFR-TKI.
6. Sabaraha lami saatos nyandak osimertinib bakal ngembangkeun résistansi ubar?
Osimertinib mangrupikeun ubar target EGFR-TKI generasi katilu kalayan rata-rata tahan résistansi ubar sakitar 11 bulan. Nanging, dina aplikasi klinis, seueur pasién ogé ngembangkeun mutasi résistansi saatos dua atanapi tilu taun saatos nyandak osimertinib, janten Kaayaan spésifik waktos résistansi oxitinib beda-beda ti jalma ka jalma.
7. Naon mékanisme résistansi ubar tina osimertinib?
Mékanisme résistansi ubar tina osimertinib rumit pisan, kalebet mutasi C797S, amplifikasi MET / pangaturan ulang RET / pangaturan ulang ROS-1, amplifikasi HER-2, mutasi BRAF, mutasi RAS, mutasi FGFR1, konversi kanker paru sél alit, teu aya genetik mutasi, sareng sajabana, sareng réimen ubar salajengna pikeun mékanisme résistansi ubar anu béda-béda.
1. Mutasi gén EGFR deui: EGFR796 sareng 797 mutasi nyatakeun 24.7%, mutasi EGFR 792 nyatakeun 10.8%, EGFR 718 sareng 719 mutasi nyatakeun 9.7% -GÉFR gén, mutasi tahan deui, nyatakeun 45% sadaya pasién, caket satengah nagara.
2. Mutasi gén sanés: kalebet PIK3CA, BRAF, MET, RET, KRAS, sareng sajabana Rupa-rupa gén supir kanker paru-paru umum sareng teu umum kalibet sareng langkung sumebar.
3. Dirobih janten kanker paru-paru sél alit.
8. Naon anu kedah dilakukeun saatos Terapi sasaran Oxitinib pikeun résistansi ubar?
Pikeun gén résistansi anu béda, solusi awal sapertos kieu:
1. Pikeun kasus mutasi triple (C797S / T790M / 19-del), pangaruh milih bugatinib langkung saé tibatan osimertinib / gefitinib, sareng pangaruhna henteu kapangaruhan ku lokasi spatial C797S sareng T790M. (1) Bugatinib digabungkeun sareng kelas anti-EGFR (cetuximab / panitumumab) tiasa ningkatkeun pangaruh terapi tina triple mutation, sareng gabungan dua ubar tiasa maénkeun pangaruh sinergis; (2) Bugatinib digabungkeun sareng Selumetinib (Simetinib) tiasa tiasa ngungkulan résistansi osimertinib anu disababkeun ku mutasi C797S.
2. Pikeun susunan trans-EGFR C797S, pertimbangkeun ubar target generasi kahiji digabungkeun sareng ubar target generasi katilu, sapertos osimertinib digabungkeun sareng gefitinib / erlotinib. Pikeun cis-alignment, anjeun tiasa
milih ubar sasaran Bugatinib + VEGF.
3. Upami ngan ukur aya mutasi C79CS, anjeun tiasa nganggo sambetan EGFR generasi kahiji, sapertos gefitinib, erlotinib, icotinib.
4. amplifikasi MET nunjukkeun yén osimertinib digabungkeun sareng sambetan MET (camatinib, crizotinib, Savolitinib, jst.). Mutasi BRAF nunjukkeun yén osimertinib digabungkeun sareng sambetan BRAF (dalafinib + trametinib). Mutasi RET nunjukkeun yén Osimertinib digabungkeun sareng Kabotinib, sareng tangtosna langkung saé Osimertinib digabungkeun sareng BLU-667.
Disarankeun yén saatos résistansi oxetinib, langkung saé dilakukeun tes genetik deui, sareng pilih ubar sasaran anu cocog numutkeun target mutasi pikeun ngabantosan perawatan anu hadé. Langkung saé konsultasi ka dokter ahli pikeun terapi kombinasi ubar sasaran.
9. Pangaruh samping tina kanker sasaran sél paru-paru sanés alit
Target ubar target molekular jelas, tapi henteu hartosna teu aya réaksi ngarugikeun klinis. Réaksi ngarugikeun obat anu ditujukeun sapertos diare, proteinuria, tekanan darah tinggi, baruntus sapertos jarawat sareng panyakit jantung dipikaterang. Sanaos ubar anu ditargét langkung handap dibanding ubar sitotoksik tradisional, éta tetep henteu kedah diremehkeun. Sababaraha réaksi ngarugikeun langka sering sesah didiagnosa kusabab diagnosis klinis, sering nyababkeun akibat serius.
Salaku conto, perlakuan erlotinib tiasa nyababkeun éléptém transaminase ati asimtomatik, sareng perdarahan gastrointestinal jarang dilaporkeun, sedengkeun gefitinib mangrupikeun terapi molekul anti-EGFR anu ditargét alit, sanaos metabolisme na utamina ati Kira-kira 4% diberesihan ku ginjal dina bentuk prototipe sareng metabolit, sareng sacara klinis rawan gagal ginjal akut, anu ningkat saatos ditarikna ubar. Dina terapi ubar anu ditujukeun, réaksi ngarugikeun anu parah bahkan nepi ka tiwasna kedah dihindari sabisa-bisa. Réaksi ngarugikeun bakal mangaruhan kayakinan sabar dina pangobatan. Réaksi ngarugikeun serius tiasa ngaganggu prosés pangobatan.
