Inkinga yomdlavuza wamaphaphu
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 umdlavuza wamaphaphu 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.
Izimbangela zomdlavuza wamaphaphu
The main causes of lung cancer include smoking, environmental pollution, occupational exposure, chronic lung disease, and genetic susceptibility. Among them, smoking is the first high-risk factor for the incidence of lung cancer. More than 80% of lung cancers are considered to be caused by smoking, and smokers are more than 10 times more likely to develop lung cancer than non-smokers. Women who do not smoke will have a 30% increased risk of lung cancer because their husband smokes. In particular, the “three 20” population, that is, people who have smoked for more than 20 years, people who have started smoking before the age of 20, and people who smoke more than 20 cigarettes a day are all high-risk groups for lung cancer. Because of very high number of smoker’s in India, incidence of lung cancer here is very high.
Izici zemvelo ezinjengokubhema, ukuvezwa emsebenzini, kanye nokungcoliswa kwemvelo kuzoba "ne-pathogenicity" ehlukile kubantu abanezizinda ezihlukile zofuzo; isibonelo, abanye abantu bahlangabezana nezimo "ezintathu ezingama-20" kepha ngeke bathole umdlavuza wamaphaphu, kanti abanye Banomdlavuza wamaphaphu. Ngokofuzo biza lo mehluko ngokuthi “ukuthambekela kofuzo”.
Ukutholakala komdlavuza wamaphaphu
Ukuthambekela kofuzo kusho ukuthi ngenxa yethonya lezici zofuzo, noma ukukhubazeka okuthile kofuzo, inezici zokuthambekela ezifweni ezithile. Njengoba kushiwo ngenhla, lapho abantu abahlukene bebhema inani elifanayo, abanye abantu baba nomdlavuza wamaphaphu kanti abanye abantu abanawo umdlavuza wamaphaphu. Lokhu kunganqunywa ukuthambekela kofuzo. Ukutholakala kofuzo lomdlavuza wamaphaphu kungenye inkambu ebalulekile yocwaningo lomdlavuza wamaphaphu. Yize iningi lomdlavuza wamaphaphu ungahlobene nezici eziqondile zofuzo ngaphandle kweminye imidlavuza yamaphaphu yomndeni, ngokusebenzisa izindlela zocwaningo zokuhlaziywa kwenhlangano ebanzi, ososayensi bathole amaGenesis kanye ne-loci ahlobene nokutholakala kofuzo lomdlavuza wamaphaphu.
Umndeni we-cytochrome P450 yi-enzyme ebalulekile ye-oxidative ehilelekile ekuguqulweni kwemithi eminingi ebalulekile. Amalungu amaningana omndeni wawo, i-CYP1A1, i-CYP1B1, i-CYP2D6, ne-CYP2A13, anamasayithi amaningi kwizakhi zofuzo ezihlotshaniswa nengozi yomdlavuza wamaphaphu. Lokhu kuhlobene namandla we-metabolic wamakhemikhali alethwe emzimbeni njengokubhema kanye nokungcola kwemvelo: abantu abanamandla amancane emethabolikhi bangase babe nethuba lokuqongelela izinto ezinjenge-polycyclic aromatic hydrocarbons (PAH), ezingadala ukulimala kwezicubu zamaphaphu.
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 isisu production, but mutants may lose or reduce the function of the enzyme, thereby prone to tumors.
Vele, kusenezifundo eziningi mayelana nokuthambekela kofuzo okuhlobene nomdlavuza wamaphaphu, futhi nazi ezimbalwa nje. Kukholakala ukuthi ngokwanda kocwaningo, kuzokhonjwa izakhi zofuzo ezithinta umdlavuza wamaphaphu, kanti nobudlelwano phakathi kwalezi zindawo ezibucayi kanye nomdlavuza wamaphaphu ozovela nawo buzovezwa kancane kancane.
Umuthi oqondile womdlavuza wamaphaphu
“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 umdlavuza wamaphaphu weselula ongewona omncane (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.
I-Egfr
Epidermal growth factor receptor (EGFR) and its family members play an important carcinogenic role by regulating cell proliferation, apoptosis, migration and tumor angiogenesis. Changes in EGFR signaling molecules involve the occurrence and development of various malignant tumors. Although the mechanism by which EGFR mutations cause cancer is not fully understood, it is clear that EGFR mutations can enhance tyrosine protein kinase activity.
E-United States nase-Asia, iziguli ezingaba ngu-10% no-35% ezinomdlavuza ongewona omncane wamangqamuzana wamaphaphu zinezinguquko ze-EGFR. Lezi zinguquko zenzeka kakhulu kuma-exon 18-21, lapho cishe u-90% wezinguquko kungu-exon 19 ukususwa noma izinciphiso. Indodana 21 L858R iphuzu ukuguqulwa. Lokhu kuguquka kwandisa umsebenzi we-EGFR kinase, okuholela ekusebenzeni kwemigwaqo yokusayina esezansi. Ezimweni eziningi, ukuguqulwa kwe-EGFR kuvame ukuhambisana nezinye izinhlobo zokuguqulwa noma ukuhlelwa kabusha, njengokuguqulwa kwe-KRAS nokuhlelwa kabusha kwe-ALK.
At present, the molecular targeted drugs developed for EGFR are mainly divided into two categories: 1. Small molecule tyrosine kinase inhibitors (TKI), such as gefitinib and erlotinib, and icotinib independently developed in China , The three can inhibit the activity of tyrosine kinase in EGFR intracellular domain; 2. Monoclonal antibody drugs (mAb), such as cetuximab and panitumumab, both of which bind to the extracellular domain of EGFR, blocking depends on EGFR activation of the ligand. The above drugs block EGFR-mediated intracellular signaling pathways through intracellular and extracellular pathways, respectively, thereby inhibiting tumor cell growth and migration, promoting tumor cell apoptosis, and increasing chemotherapy sensitivity.
IKRAS
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 i-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.
I-K-ras protein nayo iyisilawuli esibalulekile ezansi nomgwaqo osayina we-EGFR. Ngemuva kokuguqulwa kohlobo lwe-K-ras, luhlala lusesimweni esivumelekile, ngakho-ke aluthinteki yisiginali esenyakatho ye-EGFR. Kulesi sifundazwe, ukwelashwa ngezidakamizwa eziqondiswe ku-EGFR akuvumelekile. Indlela ejwayeleke kakhulu yokushintshwa kwe-carcinogenic kuhlobo lwe-K-ras ukuguqulwa kwamaphoyinti kuma-codon 12, 13 no-61 ku-N-terminus, kanye nokuguqulwa kwama-codon 12 yikhona okuvame kakhulu.
I-BRAF
I-BRAF (i-murine sarcoma filter toxin (v-raf) i-carcinogen homolog B1) yindawo yofuzo
ted engezansi kwe-KRAS ku-EGFR signaling pathway futhi ifaka ikhodi ye-serine / threonine protein kinase endleleni ye-MAPK. I-enzyme idlulisa isignali isuka ku-RAS iye ku-MEK1 / 2, bese ibamba iqhaza ekulawuleni imicimbi eyahlukahlukene yeseli.
Amaqembu ocwaningo ekhaya nakwamanye amazwe abike ukuthi i-BRAF inezilinganiso ezahlukahlukene zokuguquka komdlavuza wamaphaphu. Lezi zinguquko zenzeka kakhulu esifundeni sokuvula se-exon 15, futhi cishe ama-92% azo ayetholakala kwi-nucleotide 1799 (T mutation to A), okuholele ekufakweni kwe-glutamic acid (V600E) ye-valine encoded. Lokhu kuguquka kungadala ukuthi iziguli zihlakulele ukumelana nemithi elwa namagciwane njenge-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 i-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.
Izilingo zomtholampilo zikhombisile ukuthi ngemuva kokusebenzisa i-ceritinib ezigulini eziyi-180 ezinomdlavuza wamaphaphu ongewona omncane we-ALK, iziguli ezingama-60% zinezidakamizwa eziphumelelayo, lapho iziguli eziyi-121 ezazithole i-crizotinib ngaphambilini zazinezinga lokuphendula elingu-55.4%, 59 iziguli ezingakatholi ukwelashwa zinezinga lokuphendula elingu-69.5%. PD-L1 PDCD1 (Progammed cell death1, PD1) gene encode an immunoglobulin superfamily type I transmembrane glycoprotein, which is associated with its ligands PD-L1, PD- The combination of L2 has an inhibitory effect on the activation of lymphocytes, mediates the negative isignali elawula ukuphendula komzimba, futhi inciphisa i-apoptosis yamaseli we-anti-tumor T. I-PD1 ingalawula futhi amaseli we-T akhethekile e-antigen kuma-lymph node ngokulawula isakhi sofuzo se-Bcl-2. Ukuqongelela. Idlala indima ethile yokulawula ku-tumorigenesis, ukutheleleka ngegciwane kanye nezifo ezizimele. I-PD1 ne-ligand PD-L1 yayo ingeyemolekyuli yokuvuselela umfutho yomndeni we-B7. Le molekyuli inephrofayili ebanzi yokuveza izicubu kanye nokubonakaliswa okuphezulu kolunye ulayini weseli le-tumor. Ucwaningo oluningi lukhombisile ukuthi luhlobene nendlela yokuphunyuka kwamagciwane emathunjini. Indlela yokusayina exhunyaniswe yi-PD1 kanye ne-ligand PD-L1 yayo iba ngenye yezindlela zokwelashwa kwezifo zokwelashwa ngokungenelela komzimba.
PD-L1
Protein molecules are hardly expressed in normal tissues, but they are ubiquitous on the surface of human lung cancer, umdlavuza wesibeletho, 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. Leli yisu eliphumelela kakhulu le-immunotherapy lazo zonke izinhlobo zamathumba, ngezinga lokuphendula lesimila eliqhubekayo lika-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 umdlavuza webele 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.
Ukuvimbela umdlavuza wamaphaphu
Ukuvimbela umdlavuza wamaphaphu ngokwesayensi, ngaphezu kokwenqaba ukubhema okusebenzayo nokungathathi ntweni, ukunaka nokuphatha ngenkuthalo izifo ezingalapheki zamaphaphu, ukunciphisa ukungcoliswa komoya kwangaphakathi nangaphandle, nokugcina umoya omncane ngemuva kokungenisa umoya, kufanele kwenziwe ukuhlolwa kwezokwelapha njalo ngonyaka. Ukuthandwa kwalokhu kudlale indima ebalulekile ekutholeni umdlavuza wamaphaphu kusenesikhathi. Kubantu abajwayelekile, ukuqonda imvelaphi yabo yofuzo kanye nokuzazi kwabo kuzonikeza isiqinisekiso sempilo enempilo.
