Dambudziko rekenza yemapapu
Perhaps it is because of the direct feeling of the respiratory system. As the haze continues, we feel more and more people suffering from lung cancer around us. Indeed, lung cancer is the fastest growing malignant tumor in the world. The incidence and mortality of kenza yemapapu are the first among men, and the incidence and mortality of women are the second. Every year on November 17th is the “International Lung Cancer Day”, and 2015 is the “First Year of Precision Medicine”. We hope that on this special day, we will pass on more lung cancer knowledge to people with lung cancer patients around us: lung cancer is not Incurable disease, scientific prevention and treatment of lung cancer, starting from understanding lung cancer.
Zvinokonzera kenza yemapapu
Zvikonzero zvikuru zvegomarara remapapu zvinosanganisira kusvuta, kusvibiswa kwezvakatipoteredza, kuratidzwa pabasa, chirwere chemapapu chisingaperi, uye genetic susceptibility. Pakati pavo, kusvuta ndiyo yekutanga-yepamusoro-ngozi chinhu chekuitika kwekenza yemapapu. Inopfuura 80% yekenza yemapapu inofungidzirwa kuti inokonzerwa nekusvuta, uye vanosvuta vane mukana wakapetwa ka10 wekuita kenza yemapapu pane vasiri kuputa. Vakadzi vasingasvuti vanova nechikamu che30% panjodzi yegomarara remapapu nekuti murume wavo anosvuta. Zvikurukuru, chiverengero chavagari vapasi “vatatu makumi maviri,” ndiko kuti, vanhu vakasvuta kwaanopfuura makore 20, vanhu vakatanga kusvuta vasati vasvika makore 20 ezera, uye vanhu vanosvuta midzanga inopfuura 20 pazuva vose mapoka ari mungozi huru. yekenza yemapapu. Nekuda kwenhamba yakakwira kwazvo yevanoputa muIndia, chiitiko chekenza yemapapu chakakwira zvakanyanya.
Zvinhu zvakatipoteredza senge kuputa fodya, kusvibiswa kwebasa, uye kusvibiswa kwezvakatipoteredza zvichave ne "pathogenicity" dzakasiyana kune vanhu vane akasiyana magene; semuenzaniso, vamwe vanhu vanosangana ne "matatu makumi maviri" mamiriro asi havazowana gomarara remapapu, nepo vamwe vaine Gomarara remapapu. Genetically inodaidza uyu musiyano "genetic susceptibility".
Kenza yemapapu inobatwa
Kufungidzirwa kwemajini kunoreva kuti nekuda kwesimba remajini, kana chimwe chiremara, rine hunhu hwekugara uine zvimwe zvirwere. Sezvambotaurwa pamusoro apa, kana vanhu vakasiyana vachisvuta zvakaenzana, vamwe vanhu vanoita gomarara remapapu uye vamwe vanhu havana gomarara remapapu. Izvi zvinogona kutariswa nehunhu hunobatika. Iko kunokonzerwa nekenza yemapapu yemapapu ndeimwe nzvimbo yakakosha yekutsvaga kenza yemapapu. Kunyangwe mazhinji ekenza yemapapu isingaenderane neakananga majini kunze kwemamwe maronda emukenza emapapu, kuburikidza nenzira dzekutsvaga kwejenome-wide association analysis, masayendisiti akawana mamwe maGenesis uye loci ane hukama nehutachiona hwehutachiona hwemapapu.
Iyo cytochrome P450 mhuri yakakosha inokanganisa metabolic enzyme inobatanidzwa mune metabolism yezvakawanda zvakakosha zvinodhaka. Nhengo dzinoverengeka dzemhuri yadzo, CYP1A1, CYP1B1, CYP2D6, uye CYP2A13, dzine nzvimbo dzakawanda pamajene anosangana nenjodzi yekenza yemapapu. Izvi zvinoenderana nekwaniso yemagetsi yemakemikari akaunzwa mumuviri senge kusvuta uye kusvibisa kwezvakatipoteredza: vanhu vane hushoma hutachiona hwemagetsi vanogona kuve vanokwanisa kuunganidza zvinhu zvakaita se polycyclic inonhuhwirira yemahydrocarbon (PAH), ayo anogona kukonzera kukuvara kwemaviri emapapu.
In addition, a cohort study of 5,739 patients with sporadic lung cancer and 5,848 healthy controls controlled the genetic susceptibility site at the rs2736100 (TERT) site on chromosome 5, and the TT genotype at this site was associated with a high incidence of lung cancer. TERT is a telomerase reverse transcriptase, under physiological conditions, it inhibits tumarara production, but mutants may lose or reduce the function of the enzyme, thereby prone to tumors.
Ehe, pachine zvimwe zvidzidzo zvakawanda pamusoro pehutachiona hwehukama hune chekuita nekenza yemapapu, uye heano angori mashoma. Zvinotendwa kuti nekudzika kwekutsvagisa, mamwe majekiseni ekubatwa nekenza yemapapu anozoonekwa, uye hukama pakati penzvimbo dzinoonekera pamwe nekenza yemapapu inozoburitswa zvishoma nezvishoma.
Kuchengetedza mishonga yekenza yemapapu
“Precision medicine” is an emerging method of disease prevention and treatment, which is based on understanding the individual’s genes, environment and lifestyle. At present, precision medicine is the most mature, or the most effective, is isina-diki kenza yemapapu kenza (NSCLC), which accounts for more than 80% of lung cancer. Surgery is still the most effective treatment, but it is only suitable for a small number of patients with non-localized metastases in NSCLC, and many patients will still relapse after surgery. In recent years, the role of epidermal growth factor receptor (EGFR) in the tumorigenesis of lung cancer and targeted therapy for EGFR are gradually being clinically recognized. Clinically reasonable screening of EGFR targeted therapy targets and determination of test results play an extremely important role in treatment The important role becomes the key to treatment. At the same time, KRAS and BRAF mutations and ALK gene rearrangement and the role of PD-L1 gene in lung cancer targeted therapy have also been gradually recognized clinically.
Egfr
Epidermal growth factor receptor (EGFR) uye nhengo dzemhuri yavo vanoita basa rakakosha recarcinogenic nekudzora kuwanda kwesero, apoptosis, kutama uye bundu angiogenesis. Shanduko muEGFR yekusaina mamorekuru anosanganisira kuitika uye kukura kweakasiyana mamota anouraya. Kunyangwe iyo nzira iyo EGFR shanduko inokonzera cancer isinganzwisisike zvizere, zviri pachena kuti EGFR shanduko inogona kuwedzera tyrosine protein kinase basa.
MuUnited States neAsia, vanenge 10% uye 35% yevarwere vane isina-diki maseru kenza yemapapu vane EGFR shanduko. Shanduko idzi dzinowanzoitika mumabhenoni 18-21, ayo angangoita makumi mapfumbamwe kubva muzana ekuchinja kuri exon 90 kubviswa kana exon. Mwanakomana 19 L21R poindi mutation. Izvi zvinoshandura zvinowedzera EGFR kinase chiitiko, zvichitungamira mukumisikidzwa kwenzizi dzekuratidzira nzira. Muzviitiko zvakawanda, EGFR shanduko inowanzo kuperekedzwa nedzimwe mhando dzekuchinja kana kugadzirisazve, senge KRAS mutations uye ALK rearrangements.
Parizvino, mishonga inotarirwa nemakemikari yakagadzirirwa EGFR inonyanya kugoverwa muzvikamu zviviri: 1. Small molecule tyrosine kinase inhibitors (TKI), yakadai se gefitinib uye erlotinib, uye icotinib yakazvimiririra yakagadzirwa muChina, Izvo zvitatu zvinogona kudzivisa basa re tyrosine kinase. muEGFR intracellular domain; 2. Monoclonal antibody drugs (mAb), yakadai secetuximab uye panitumumab, iyo yose inosunga kune extracellular domain yeEGFR, kuvhara kunoenderana neEGFR activation ye ligand. Mishonga iri pamusoro inovharira EGFR-mediated intracellular signing pathways kuburikidza neintracellular uye extracellular pathways, zvichiteerana, nekudaro ichidzivirira bundu cell kukura uye kutama, kukurudzira bundu cell apoptosis, uye kuwedzera chemotherapy senitivity.
SKRATCH
RAS is a common oncogene in human tumors. The genes associated with human tumors in the RAS gene family are composed of K-ras, H-ras and N-ras. Among them, K-ras (v-Ki-ras2 murine Kirsten sarcoma virus oncogene The highest mutation rate of homologues is 17-25%; at the same time, the K-ras gene is also the oncogenic gene with the highest mutation frequency in all tumors, and about 10-20% of tumors are related to the abnormal activation of K-ras. Can control the path of cell growth; when abnormal, it causes the cell to continue to grow and prevent apoptosis, which in turn leads to cancer.
K-ras protein zvakare iri yakakosha mutongi muzasi kwerwizi rweEGFR yekuratidzira nzira. Mushure mekuchinja kweiyo K-ras geni, inogara iri munzvimbo yakamisikidzwa, saka haina kukanganiswa nechiratidzo chekumusoro cheEGFR. Mune ino nyika, kurapwa neEGFR yakanangwa nemishonga hakushande. Nzira yakajairika yekuchinja kwecarcinogen muK-ras geni inongedzo maconons 12, 13 uye 61 paN-terminus, uye macodon gumi nemaviri shanduko ndiwo akajairika.
HANZVADZI KONAMA
BRAF (murine sarcoma sefa toxin (v-raf) carcinogen homolog B1) iri geni loca
ted yekumusoro kwerwizi rweKRAS muEGFR yekuratidzira nzira uye inokomberedza iyo serine / threonine protein kinase munzira yeMAPK. Iyo enzyme inoshandura chiratidzo kubva kuRAS kuenda kuMEK1 / 2, uye nekudaro inotora chikamu mukugadzirisa zviitiko zvakasiyana siyana zvehupenyu musero.
Mapoka ekutsvagisa kumba nekune dzimwe nyika akataura kuti BRAF ine zviyero zvakasiyana zvekuchinja mukenza yemapapu. Idzi shanduko dzakanyanya kuitika munzvimbo yekumisikidza ye exon 15, uye ingangoita 92% yadzo yaive pa nucleotide 1799 (T mutation kuenda kuA), zvichikonzera kutsiva kwe glutamic acid (V600E) yevhavha yakavharidzirwa. Iyi shanduko inogona kukonzera varwere kukudziridza kuramba mishonga yeantibody secetuximab.
Verofinil is a non-receptor tyrosine kinase inhibitor that selectively inhibits the BRAF protein located at the entrance of the MAPK / ERK pathway. Approved for the treatment of malignant melanoma, it is the first approved tyrosine kinase inhibitor for tumors carrying the BRAF (V600E mutation) gene. Clinical trials have shown that the drug has an effective rate of 42.9% for patients with this melanoma, but is basically ineffective for those who have not been mutated.
ALK
The ALK (anaplastic lymphoma kinase) gene encodes a receptor tyrosine kinase and belongs to the insulin receptor superfamily. ALK proteins play an important role in brain development and can affect the nervous system of specific neurons. FDA approves ZYKADIA for patients with metastatic non-small cell lung cancer who have ALK positive progression or cannot use crizotinib, and crizotinib (XALKORI) is approved by the FDA for ALK positive non-small cell lung cancer patient. Rearranged ALK accounts for 5% of the incidence of NSCLC. In 2010, the New England Journal of Medicine reported that 82 of 1001 lung cancers were ALK-positive medications, with an effective rate of 60.8%. 347 patients with ALK positive (including platinum-based chemotherapy failure) randomized to receive crizotinib and chemotherapy significantly improved the proportion of tumor control.
Zvirwere zvemakiriniki zvakaratidza kuti mushure mekushandisa ceritinib muvarwere zana nemakumi masere vane ALK-yakasanganisa isiri-diki kenza yemapapu yemukenza, 180% yevarwere vaive nemishonga inoshanda, iyo varwere 60 vakambogamuchira crizotinib vaive nemhinduro ye121%, 55.4 varwere vasina kuwana chero kurapwa vane mukana wekupindura we59%. PD-L69.5 PDCD1 (Yakafambiswa sero kufa1, PD1) geni inodzora immunoglobulin superfamily mhando ini transmembrane glycoprotein, inosanganiswa neiyo ligands PD-L1, PD- Iko kusanganiswa kweL1 kune chinokanganisa kushanda kweiyo activation ye lymphocyte, inopindirana nezvakashata. inodzora chiratidzo chekudzivirira immune, uye inokonzeresa apoptosis yea anti-bundu T masero. PD2 inogona zvakare kudzora antigen-akasarudzika T maseru mune lymph node nekugadzirisa iyo Bcl-1 geni. Kuunganidza. Inotamba yakatarwa yekuita basa mune tumorigenesis, hutachiona hutachiona uye autoimmune hosha. PD2 uye iyo ligand PD-L1 ndeyeye-inosimudzira mamorekuru emhuri yeB1. Morekuru iri rine rakapamhamha tishu kutaura chimiro uye kukwirira kutaura pane mamwe mamota maseru mitsara. Ongororo dzakawanda dzakaratidza kuti zvine chekuita neyekudzivirira immune maitiro emamota. Iyo yekuratidzira nzira inopindirana nePD7 uye iyo ligand PD-L1 iri kuve imwe yemaitiro ekurapwa kwechirwere chechipatara kuburikidza nekupindira kwemajoni.
PD-L1
Protein molecules are hardly expressed in normal tissues, but they are ubiquitous on the surface of human lung cancer, ovarian kenza, colon cancer, renal cancer and melanoma. Studies have speculated that it can make tumor cells have the magical ability to escape immune response. . By inhibiting PD1 or PD-L1 to activate the anti-tumor activity of T cells and maintain its ability to detect and attack cancer cells, it can provide new ideas for cancer treatment. More than 200 patients with different types of tumors were enrolled in two different clinical trials. The largest cohort samples included melanoma and non-small cell lung cancer (NSCLC) patients. Both trials reported surprisingly long-lasting response rates (6–17% in the anti-PDL1 group and 18–28% in the anti-PD1 group), especially for melanoma patients (17% and 28% in both groups) , And the incidence of drug-related adverse events is also low (9% and 14% for grade 3 and 4 drug-related adverse events, respectively). More importantly, in the anti-PD1 group, the response rate of tumor patients with positive PD-L1 expression was 36%. It is worth noting that the trial purpose and sustained response rate of NSCLC patients also meet the trial requirements, and such patients are known for their resistance to immunotherapy. Iri ndiro rakanyanya kubudirira immunotherapy zano remarudzi ese emamota, ane bundu rinoramba richipindura mwero we10-15%.
As the concept of precision medicine continues to advance, the clinic has begun to use mutations to distinguish tumors rather than tissue sources. For example, if a gene mutation related to kenza yebonde targeted medication is found in lung cancer, then this breast cancer medication may be used in the treatment of lung cancer; the National Cancer Institute (NCI) has initiated related clinical research (NCI-MATCH) . I believe that in the near future, this concept will be fully practiced in the clinic.
Kudzivirira kenza yemapapu
Kudzivirira kenza yemapapu nesainzi, mukuwedzera pakuramba kusvuta uye kuputa fodya, kutarisisa uye nekushinga kurapa chirwere chisingaperi chemapapu, kudzikisira mweya wekunze nekunze, uye kuchengetedza kufefetera mushure mekufefetwa, kuongororwa kwechiremba nguva nenguva kunofanira kuitwa gore rega rega. Kuzivikanwa kweizvi kwakabata chinzvimbo chakakosha mukuonekwa kwekutanga kwekenza yemapapu. Kune vanhuwo zvavo, kunzwisisa kwavo kwehunhu uye nekuzviziva iwe kunopa vimbiso yehupenyu hwakanaka.
