Matsalar kansar huhu
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 kwayar cutar huhu 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.
Dalilin cutar kansa ta huhu
Babban abubuwan da ke haifar da ciwon daji na huhu sun haɗa da shan taba, gurɓataccen muhalli, fallasa sana'a, cututtukan huhu na yau da kullun, da kamuwa da kwayoyin halitta. Daga cikin su, shan taba shine abu na farko da ke da hatsarin kamuwa da cutar kansar huhu. Fiye da kashi 80 cikin 10 na cututtukan daji na huhu ana ɗaukar su ta hanyar shan sigari ne, kuma masu shan sigari sun fi sau 30 kamuwa da cutar kansar huhu fiye da masu shan taba. Matan da ba sa shan taba za su sami karuwar kashi 20% na cutar kansar huhu saboda mijinsu yana shan taba. Musamman, mutanen "20 20", wato, mutanen da suka sha taba fiye da shekaru 20, mutanen da suka fara shan taba kafin shekaru XNUMX, da kuma mutanen da suke shan taba fiye da XNUMX a rana duk kungiyoyi ne masu haɗari. ga ciwon huhu. Saboda yawan masu shan taba a Indiya, kamuwa da cutar kansar huhu a nan ya yi yawa sosai.
Abubuwan da ke cikin muhalli kamar shan sigari, fallasawar aiki, da gurɓatar mahalli za su sami “cutarwa” daban-daban ga mutanen da ke da asalin asalin halittar; misali, wasu mutane sun cika yanayin "uku" 20 amma ba zasu kamu da cutar sankarar huhu ba, yayin da wasu suka samu ciwon huhu. A dabi'ance ana kiran wannan bambanci "mai saukin kamuwa da kwayoyin halitta".
Mai saukin kamuwa da cutar huhu
Saukin dabi'un halitta yana nufin saboda tasirin tasirin kwayoyin, ko wani lahani na kwayoyin, yana da halaye na zama masu saurin kamuwa da wasu cututtuka. Kamar yadda aka ambata a sama, idan mutane daban-daban suka sha sigari daya, wasu mutane suna kamuwa da cutar sankarar huhu wasu kuma ba sa kamuwa da cutar huhu. Wannan na iya ƙayyadewa ta saukin yanayin ƙwayoyin halitta. Halin kwayar cutar sankarar huhu wani muhimmin fanni ne na binciken kansar huhu. Kodayake yawancin cututtukan huhu ba su da alaƙa da abubuwan da ke haifar da kwayoyin halitta kai tsaye sai dai wasu cututtukan huhu na iyali, ta hanyar hanyoyin bincike na nazarin alakar ɗumbin ɗumbin masana, masanan kimiyya sun gano wasu ƙwayoyin halitta da na alaƙa da ke da alaƙa da ƙwayoyin cututtukan huhu.
Iyalin P450 na cytochrome muhimmin enzyme ne wanda ke cikin hadahadar magunguna masu mahimmanci. Da yawa daga cikin dangin ta, CYP1A1, CYP1B1, CYP2D6, da CYP2A13, suna da shafuka da yawa akan kwayoyin halittar da ke da alaƙa da haɗarin cutar kansa ta huhu. Wannan yana da alaƙa ne da ƙarancin tasirin sinadarai da aka shigo da su cikin jiki kamar shan sigari da gurɓatar muhalli: mutanen da ke da ƙarancin yanayin rayuwa na iya samun damar tara abubuwa kamar su polycyclic aromatic hydrocarbons (PAH), wanda zai iya haifar da lalacewar ƙwayar huhu.
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 tumo production, but mutants may lose or reduce the function of the enzyme, thereby prone to tumors.
Tabbas, har yanzu akwai sauran karatu game da yanayin kwayar halittar da ke da nasaba da cutar sankarar huhu, kuma ga wasu kaɗan. An yi imanin cewa tare da zurfafa bincike, za a gano ƙarin ƙwayoyin cuta masu saurin kamuwa da cutar huhu, kuma alaƙar da ke tsakanin waɗannan rukunin yanar gizo masu saurin ji da sannu sannu a hankali za a bayyana su a hankali.
Daidaitaccen magani don cutar huhu
“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 cututtukan daji na kansa marasa kansar (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 girma factor receptor (EGFR) da 'yan uwa suna taka muhimmiyar rawa ta carcinogenic ta hanyar daidaita yaduwar kwayar halitta, apoptosis, ƙaura da ƙari angiogenesis. Canje-canje a cikin ƙwayoyin siginar EGFR sun haɗa da faruwa da haɓakar ciwace-ciwacen ƙwayoyi iri-iri. Kodayake tsarin da maye gurbi na EGFR ke haifar da ciwon daji ba a fahimta sosai ba, a bayyane yake cewa maye gurbin EGFR na iya haɓaka ayyukan kinase protein na tyrosine.
A Amurka da Asiya, kusan 10% da 35% na marasa lafiya da ke da ƙananan ƙwayoyin cuta na huhu suna da maye gurbi na EGFR. Wadannan maye gurbi galibinsu suna faruwa ne a cikin misalan 18-21, wanda kusan 90% na maye gurbi ya zama share 19 ko share. 21a 858 LXNUMXR maye gurbi. Wadannan maye gurbi suna haɓaka aikin kinji na EGFR, wanda ke haifar da kunna hanyoyin siginar ƙasa. A mafi yawan lokuta, sauye-sauyen EGFR galibi suna tare da wasu nau'ikan maye gurbi ko sake tsara su, kamar maye gurbin KRAS da sake fasalin ALK.
A halin yanzu, magungunan da aka yi niyya na kwayoyin halitta don EGFR sun kasu kashi biyu: 1. Ƙananan ƙwayoyin tyrosine kinase inhibitors (TKI), irin su gefitinib da erlotinib, da icotinib da kansu sun haɓaka a kasar Sin, ukun na iya hana ayyukan tyrosine kinase. a cikin yankin intracellular na EGFR; 2. Monoclonal antibody kwayoyi (mAb), irin su cetuximab da panitumumab, dukansu sun ɗaure zuwa yankin extracellular na EGFR, toshewa ya dogara da kunna EGFR na ligand. Magungunan da ke sama suna toshe hanyoyin siginar siginar ciki na EGFR ta hanyar intracellular da extracellular, bi da bi, ta haka ne ke hana haɓakar ƙwayar ƙwayar cuta da ƙaura, haɓaka apoptosis cell tumor, da haɓaka ilimin chemotherapy.
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.
Furotin na K-ras kuma babban mai sarrafawa ne a ƙasan hanyar siginar EGFR. Bayan maye gurbi na kwayar K-ras, koyaushe yana cikin yanayin kunnawa, don haka siginar sama na EGFR baya shafar shi. A cikin wannan jihar, jiyya tare da magungunan EGFR ba daidai bane. Hanyar da ta fi dacewa ta maye gurbi a cikin kwayar K-ras ita ce maye gurbi a lamba 12, 13 da 61 a N-terminus, kuma maye gurbin codon 12 sun fi yawa.
Farashin BRAF
BRAF (murine sarcoma tace toxin (v-raf) carcinogen homolog B1) asalin yanki ne
saukar da ƙasan KRAS a cikin hanyar siginar EGFR kuma yana sanya serine / threonine protein kinase a cikin hanyar MAPK. Enzyme din yana watsa sigina daga RAS zuwa MEK1 / 2, don haka yana shiga cikin daidaita abubuwan da ke faruwa a cikin kwayar halitta.
Kungiyoyin bincike a cikin gida da waje sun ba da rahoton cewa BRAF yana da nau'ikan yanayin maye gurbi a cikin cutar sankarar huhu. Wadannan maye gurbi sun fi faruwa a yankin kunnawa na exon 15, kuma kusan kashi 92 cikin 1799 daga cikinsu an same su ne a nucleotide 600 (T maye gurbi zuwa A), wanda ya haifar da maye gurbin glutamic acid (VXNUMXE) don ɓoyayyen valine. Wannan maye gurbi na iya haifar da rashin lafiya ga kwayoyi masu hana yaduwar kwayoyi kamar 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 linzoma 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.
Gwaje-gwajen asibiti sun nuna cewa bayan amfani da ceritinib a cikin marasa lafiya 180 tare da ALK-hade da ƙananan ƙwayoyin cuta na huhu, 60% na marasa lafiya suna da tasirin kwayoyi masu tasiri, waɗanda marasa lafiya 121 waɗanda a da suka karɓi crizotinib a baya sun sami adadin amsa 55.4%, 59 marasa lafiya waɗanda ba su sami magani ba suna da nauyin amsa 69.5%. PD-L1 PDCD1 (Progammed cell death1, PD1) kwayar halitta mai dauke da nau'ikan dangi na immunoglobulin na transmembrane glycoprotein, wanda ke hade da ligands dinsa PD-L1, PD- Haɗin L2 yana da tasirin hanawa kan kunna ƙwayoyin lymphocytes, yana yin sulhu mara kyau siginar tsari na amsawar rigakafi, kuma yana haifar da apoptosis na ƙwayoyin T-anti-tumo. PD1 na iya sarrafa ƙwayoyin T na musamman na ƙwayoyin cuta a cikin ƙwayoyin lymph ta hanyar daidaita kwayar Bcl-2. Tarawa. Yana takaita takamaiman aikin sarrafawa a cikin tumorigenesis, cututtukan ƙwayoyin cuta da cututtukan autoimmune. PD1 da ligand PD-L1 na cikin kwayar haɓakar haɓaka ta gidan B7. Wannan kwayar tana da fadin nama mai fadi da kuma magana mai girma akan wasu layin kwayar halitta. Yawancin karatu sun nuna cewa yana da alaƙa da tsarin tsere na rigakafin ƙwayoyin cuta. Hanyar sigina ta hanyar PD1 da ligand PD-L1 tana zama ɗayan hanyoyin maganin cututtukan asibiti ta hanyar rigakafin rigakafi.
PD-L1
Protein molecules are hardly expressed in normal tissues, but they are ubiquitous on the surface of human lung cancer, ciwon daji na ovarian, 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. Wannan ita ce mafi nasarar dabarun rigakafin rigakafi na kowane nau'in ciwace-ciwacen daji, tare da ci gaba da karɓar amsawar ƙari na 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 ciwon nono 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.
Rigakafin cutar huhu
Don hana cutar kansar huhu a kimiyance, banda kin shan sigari mai aiki da zafin jiki, kula da kuma kula da cututtukan huhu na yau da kullun, rage gurɓatar iska ta cikin gida da waje, da kiyaye iska bayan iska, ya kamata a gudanar da binciken likita na yau da kullun kowace shekara. Shahararren wannan ya taka muhimmiyar rawa a farkon gano kansar huhu. Ga talakawa, fahimtar asalinsu da sanin yakamata zai ba da tabbaci ga rayuwa mai ƙoshin lafiya.
