Dhibaatada kansarka sanbabka
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 kansarka sanbabada 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.
Sababaha kansarka sanbabka
Sababaha ugu waaweyn ee kansarka sanbabada waxaa ka mid ah sigaar cabista, wasakhowga deegaanka, soo-gaadhista shaqada, cudurrada sambabada ee raaga, iyo u nuglaanshaha hidda-socodka. Waxaa ka mid ah, sigaarku waa qodobka ugu horreeya ee khatarta sare leh ee dhacdooyinka kansarka sanbabada. In ka badan 80% kansarka sanbabada ayaa loo arkaa inay ka dhashaan sigaar cabista, dadka sigaarka cabba ayaa 10 jeer ka badan ugu dhow inuu ku dhaco kansarka sanbabada marka loo eego kuwa aan sigaarka cabbin. Dumarka aan sigaarka cabbin waxay yeelan doonaan 30% khatarta kansarka sanbabada sababtoo ah ninkooda ayaa sigaarka cabba. Gaar ahaan, dadka "saddexda 20", taas oo ah, dadka sigaarka cabba in ka badan 20 sano, dadka bilaabay sigaar cabista ka hor da'da 20 sano, iyo dadka cabba in ka badan 20 sigaar ah maalintii waa dhammaan kooxaha khatarta sare leh. kansarka sanbabada. Sababtoo ah tirada aadka u badan ee sigaarka cabba ee Hindiya, dhacdooyinka kansarka sanbabada halkan aad bay u badan yihiin.
Waxyaabaha deegaanka sida sigaar cabista, soo-gaadhista shaqada, iyo wasakheynta bey'adda waxay lahaan doonaan "cuduro" kala duwan oo loogu talagalay dadka leh hiddo-wadaha kala duwan; tusaale ahaan, dadka qaar waxay buuxiyaan shuruudaha "saddexda 20" laakiin ma yeelan doonaan kansarka sanbabada, halka qaar kalena ay heleen kansarka sanbabada. Hiddo ahaan ugu yeer farqigaas "u nuglaanta hidde-wadaha".
U nuglaanshaha kansarka sanbabka
U nuglaanta hidde-wadaha micnaheedu waa saameynta sababaha hidda-wadaha, ama cillad hidde ahaan u gaar ah, waxay leedahay astaamo u nugul cudurrada qaarkood. Sida aan kor ku soo sheegnay, marka ay dadka kala duwan cabbaan isla qaddarka, dadka qaar waxaa ku dhaca kansarka sambabka dadka qaarna kuma dhacaan kansarka sanbabada. Tan waxaa lagu go'aamin karaa u nuglaanta hidda-socodka. U nuglaanta hidde-wadaha kansarka sambabka waa qayb kale oo muhiim ah oo baaritaanka kansarka sanbabada. In kasta oo inta badan kansarrada sanbabadu aysan xiriir la lahayn arrimo hidde toos ah marka laga reebo qaar ka mid ah kansarka sambabaha qoysaska, iyada oo loo marayo hababka cilmi-baarista ee falanqaynta jimicsiga guud, saynisyahannadu waxay heleen qaar ka mid ah hiddo-wadaha iyo lahjadda la xiriirta u nuglaanshaha hidde-wadaha kansarka sanbabada.
Qoyska cytochrome P450 waa enzyme muhiim u ah oksaydh ku lug leh dheef-shiid kiimikaad daroogooyin badan oo muhiim ah. Dhowr xubnood oo ka tirsan qoyskooda, CYP1A1, CYP1B1, CYP2D6, iyo CYP2A13, waxay leeyihiin goobo badan oo ku saabsan hiddo-wadaha la xiriira halista kansarka sanbabada. Tani waxay la xiriirtaa awoodda dheef-shiid kiimikaad ee kiimikooyinka la keeno jirka sida sigaar cabbidda iyo wasakheynta deegaanka: dadka leh awood dheef-shiid kiimikaad hooseeya waxay u badan tahay inay urursadaan walxo ay ka mid yihiin polycyclic aromatic hydrocarbons (PAH), oo u horseedi kara dhaawac unugyada sambabka.
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 buro production, but mutants may lose or reduce the function of the enzyme, thereby prone to tumors.
Dabcan, weli waxaa jira daraasado badan oo ku saabsan u nuglaanshaha hidde-wadaha ee la xiriira kansarka sanbabada, oo halkan waxaa ku yaal dhowr ka mid ah. Waxaa la rumeysan yahay in sii xoojinta cilmi baarista, hiddo-wadayaal u nugul kansarka sanbabada la ogaan doono, iyo xiriirka ka dhexeeya goobahan xasaasiga ah iyo kansarka ugu dambeeya ee kansarka ayaa sidoo kale si tartiib tartiib ah loo soo bandhigi doonaa.
Daawada saxda ah ee kansarka sanbabada
“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 kansarka sanbabada ee aan yareyn (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
Soo-dhowaynta kobaca Epidermal (EGFR) iyo xubnaha qoysku waxay ciyaaraan door muhiim ah oo kansarka leh iyagoo xakameynaya kororka unugyada, apoptosis, socdaalka iyo angiogenesis buro. Isbeddellada unugyada calaamadaha EGFR waxay ku lug leeyihiin dhacdooyinka iyo horumarinta burooyinka xun xun ee kala duwan. Inkasta oo habka uu isu beddelka EGFR u keeno kansar aan si buuxda loo fahmin, waxaa cad in isbeddellada EGFR ay kor u qaadi karaan dhaqdhaqaaqa kinase borotiinka tyrosine.
Mareykanka iyo Aasiya, qiyaastii 10% iyo 35% bukaannada qaba kansarka sanbabada ee unugyada yar waxay leeyihiin isbadal EGFR. Is-beddelladani waxay inta badan ku dhacaan tusaalooyinka 18 - 21, kuwaas oo qiyaastii 90% ka mid ah is-beddelka ay yihiin exon 19 tirtirid ama exons ah. Wiilka 21 L858R isbeddel dhibic. Is-beddelladani waxay kordhiyaan waxqabadka EGFR kinase, oo horseedaya kicinta dariiqyada calaamadaha hoose. Xaaladaha badankood, isbeddelada EGFR waxaa badanaa la socda noocyo kale oo isbeddello ama dib-u-habeyn ah, sida is-beddelka KRAS iyo dib-u-habeynta ALK.
Waqtigan xaadirka ah, daawooyinka molecular ee loogu talagalay EGFR waxay inta badan u qaybsan yihiin laba qaybood: 1. Unugyada yaryar ee tyrosine kinase inhibitors (TKI), sida gefitinib iyo erlotinib, iyo icotinib oo si madax-bannaan u horumariyay Shiinaha, Saddexdu waxay joojin karaan dhaqdhaqaaqa tyrosine kinase. gudaha EGFR intracellular domain; 2. Daawooyinka monoclonal antibody (mAb), sida cetuximab iyo panitumumab, labaduba waxay ku xidhan yihiin qaybta ka baxsan EGFR, xannibaadda waxay kuxirantahay firfircoonida EGFR ee ligand. Daawooyinka kor ku xusan waxay xannibaan EGFR-dhexdhexaadinta calaamadaha calaamadaha unugyada gudaha iyada oo loo marayo dariiqyada unugyada gudaha iyo kuwa ka baxsan, siday u kala horreeyaan, taas oo joojinaysa koritaanka unugyada burooyinka iyo socdaalka, kor u qaadida apoptosis unugyada burooyinka, iyo kordhinta dareenka kiimikaad.
KRAS
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.
Borotiinka K-ras sidoo kale waa xakameeye fure u ah marinka hoose ee wadada calaamadaha EGFR. Isbeddel ka dib hiddo-wadaha K-ras, had iyo jeer wuxuu ku jiraa xaalad firfircoon, marka saameyn kuma yeelanayso calaamadaha kore ee EGFR. Gobolkan, daaweynta dawooyinka la bartilmaameedsaday ee EGFR waa kuwo aan ansax ahayn. Habka ugu caansan ee isbeddelada kansarka ku dhaca hiddo-wadaha K-ras waa is-beddelka dhibcaha ee codons 12, 13 iyo 61 ee N-terminus, iyo codon 12 isbadal ayaa ugu badan.
WALAAL
BRAF (murine sarcoma filter toxin (v-raf) kansar homoglog B1) waa hiddo-wadaha
hoos udhaca KRAS ee wadada calaamadeynta EGFR waxayna codeeysaa serine / threonine protein kinase ee dariiqa MAPK. Enzyme-ka ayaa ka wareejinaya signalka RAS illaa MEK1 / 2, oo markaa ka qaybqaata hagaajinta dhacdooyinka noolaha kala duwan ee unugga.
Kooxaha cilmi-baarista ee gudaha iyo dibaddaba waxay soo sheegeen in BRAF ay leedahay heerar kala duwan oo isbeddello kansarka sanbabada ah. Isbeddelladani waxay badanaa ka dhaceen aagga firfircoonaanta ee exon 15, qiyaastii 92% ka mid ahna waxay ku yaalliin nukleotide 1799 (T mutation to A), taasoo keentay beddelidda glutamic acid (V600E) ee loo yaqaan 'valine encoded'. Isbeddelkan wuxuu sababi karaa bukaanjiifka inay yeeshaan iska caabin ka hortagga daroogada sida cetuximab.
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 qanjiro 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.
Tijaabooyin caafimaad ayaa muujiyay in ka dib markii loo isticmaalay ceritinib in 180 bukaan ah oo leh kansarka sanbabada ee unugyada yar yar ee ALK, 60% bukaanada ay leeyihiin falcelin daroogo oo wax ku ool ah, kuwaas oo 121 bukaan ah oo horey uhelay crizotinib ay heleen jawaab celin ah 55.4%, 59 bukaanka aan helin wax daaweyn ah waxay leeyihiin jawaab celin ah 69.5%. PD-L1 PDCD1 (Progammed cell death1, PD1) hidde wuxuu xiraa nooca 'immunoglobulin superfamily type I transmembrane glycoprotein', kaas oo laxiriira xididadiisa 'PD-L1, PD- Isku darka L2 wuxuu leeyahay saameyn xaddidan oo ku saabsan firfircoonida' lymphocytes ', wuxuu dhexdhexaadiyaa diidmada calaamadda sharciyeynta ee jawaab celinta difaaca jirka, waxayna keentaa apoptosis-ka unugyada anti-tumor T. PD1 sidoo kale waxay xakamayn kartaa unugyada T-ga ee gaarka u ah unugyada qanjirada iyadoo la nidaaminayo hidda-wadaha Bcl-2. Iskudhin Waxay ka ciyaareysaa door sharciyeed qaas ah oo ku saabsan tumorigenesis, infekshannada fayraska iyo cudurada iswada. PD1 iyo ligand-kiisa PD-L1 waxay ka tirsan yihiin molecule wada-kiciyaha ee qoyska B7. Molikiyuulkani wuxuu leeyahay muuqaal ballaaran oo muujinta nudaha ah iyo muujinta sare ee khadadka unugyada burooyinka qaarkood. Daraasado badan ayaa muujiyay inay la xiriirto habka baxsashada difaaca ee burooyinka. Wadada calaamadeynta ee ay dhexdhexaadineyso PD1 iyo xariggeeda PD-L1 waxay noqoneysaa mid ka mid ah hababka daaweynta cudurka daaweynta iyadoo loo marayo faragelinta difaaca jirka.
PD-L1
Protein molecules are hardly expressed in normal tissues, but they are ubiquitous on the surface of human lung cancer, kansarka ugxansiduhu, 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. Tani waa ilaa hadda istaraatijiyadda difaaca jirka ee ugu guusha badan dhammaan noocyada burooyinka, oo leh heerka jawaab celinta burada joogtada ah ee 10-15%.
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 kansarka naasaha 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.
Kahortaga kansarka sanbabada
Si looga hortago kansarka sanbabada si cilmiyaysan, marka lagu daro diidmada sigaarka firfircoon iyo kuwa dadban, u fiirsashada iyo firfircoonida daaweynta cudurada sanbabada ee daba dheeraada, yareynta wasakheynta hawada gudaha iyo dibada, iyo ilaalinta hawo qaadashada ka dib hawada, baaritaan caafimaad oo joogto ah waa in la sameeyaa sanad kasta. Caan ka noqoshada tani waxay door muhiim ah ka ciyaartay baaritaanka hore ee kansarka sanbabada. Dadka caadiga ah, fahamka asalkooda hidde iyo is-baraarujintu waxay siin doontaa dammaanad-qaad nolol caafimaad leh.
