Immunotherapy uses drugs to help the body’s own immune system better recognize and destroy cancer cells. Immunotherapy can be used to treat patients with advanced colorectal cancer.
Immune checkpoint inhibitor
Chikamu chakakosha chemuviri wemuviri kugona kwayo kuzvidzivirira kubva pakurwisa masero akajairwa nemuviri. Kune izvi, inoshandisa "cheki yekuongorora" mapuroteni pane maseru ezvirwere, anoita senge switch dzinofanirwa kuvhurwa (kana kudzimwa) kutanga mhinduro yemumuviri.
Cancer maseru dzimwe nguva anoshandisa aya ekuongorora kumisa immune system kubva pakuvarwisa. Nekudaro, mishonga yakanangana nenzvimbo dzekuongorora idzi ine tarisiro huru senzira dzekurapa gomarara.
Zvinodhaka zvinodaidzwa kuti checkpoint inhibitors zvinogona kushandiswa muvanhu vane maseru emukenza macolorectal vakaedza kuita zvakanaka kune mamwe majini ekushanduka, senge yakakwira microsatellite kusagadzikana (MSI-H), kana imwe yemhando dze mismatch kugadzirisa (MMR) Genetic shanduko.
These drugs are used in people whose cancer is still growing after chemotherapy. They may also be used to treat people whose cancer cannot be removed surgically, relapses after treatment (relapse) or has spread to other parts of the body (metastasis).
Approved immunotherapy zvinodhaka
PD-1 inhibitor approved
Pembrolizumab (Pembrolizumab, Keytruda) and nivolumab (Nivolumab, Opdivo) are drugs that target PD-1, a protein on cells of the immune system called T cells that usually helps Prevent these cells from attacking other cells in the body. By blocking PD-1, these drugs can enhance the immune response to cancer cells.
On May 24, 2017, the US FDA approved the PD-1 inhibitor pembrolizumab (Pembrolizumab, Keytruda) for the treatment of solid tumarara patients with microsatellite highly unstable (MSI-H) / mismatch repair defects (dMMR), The tumor types cover 15 different malignant tumors, including colorectal cancer, small cell lung cancer, and cervical cancer.
Musi waAugust 2, 2017, iyo US Chikafu neDrug Administration (FDA) yakabvumidza nivolumab (Navumab, Opdivo) yekurapa fluorouracil, oxaliplatin, uye irinotecan. Microsatellite ine yakanyanya kusagadzikana (MSI -H) Kurapa kwemasastatic colorectal cancer kune vanhu vakuru kana vana (≥12 makore) kana kusakanganisa kukanganisa kuremara (dMMR).
CTLA-4 inhibitor inogamuchirwa
Ipilimumab (Yervoy) mumwe mushonga unogona kusimudzira mhinduro yemumuviri. Haigoni kushandiswa yoga. Inoda kusanganiswa nivolumab, inovhara CTLA-4, inova imwe protein pane T maseru.
Nyaya yakabudirira yeMSI-High (MSI-High) mCRC ndiko kushandiswa kwekubatana kwe nivolumab uye ipilimumab, iyo yakaongororwa muChikamu II ChekuongororaMate142 kudzidza. Musanganiswa wekurapa wakaratidza ORR (chinangwa chekupindura chiyero) che49%, uye vashanu pavane 5 varwere vaive neCR (yakazara mhinduro) uye 119 PR (mhinduro shoma). Vazhinji varwere (n = 53) vakambogamuchira fluorouracil, oxaliplatin uye irinotecan. Mune varwere ava, ORR yaive 82%, 46 CRs uye 3 PRs.
Sekureva kweCheckMate-142 dhata, iyo FDA yakabvumidza mubatanidzwa (Nivolumab + Ipilimumab) yekurapa kwevakuru uye kwevana varwere vane makore gumi nemaviri zvichikwira, kusanganisira mCRC varwere vane MSI-H kana mismatch kugadzirisa kuremara (dMMR), Varwere ava vakafambira mberi. mushure mekurapwa ne fluorouracil, oxaliplatin uye irinotecan.
Dudziro yekushandisa kweMSI / dMMR mune colorectal kurapwa
MSI inoreva kurasikirwa kwekusaenzana kwekugadzirisa magene anokonzerwa neDNA methylation kana jeni shanduko, zvichikonzera shanduko muhurefu hwe microsatellite kudzokorora kuteedzana. Chidzidzo chacho chakawana kuti MSI-H inokosha biomarker yemamota akakodzera immunotherapy.
MSI is microsatellite instability, MMR (mismatch repair) inoreva geni mismatch kugadzirisa basa. Iyo yemunhu mismatch yekugadzirisa gene (MMR gene) inogona kuratidza inoenderana mismatch yekugadzirisa mapuroteni mushure mekunyorwa uye kushandurwa. Kana kurasikirwa kwekutaura kwechero mapuroteni eMMR kunogona kukonzera kutadza musero kusarongeka kwekugadzirisa basa, iko kusanzwisisika mukuita kweDNA kudzokorodza Kurasikirwa kwekugadzirisa basa kunotungamira mukuunganidzwa, uko kunotungamira mukuitika kwekusagadzikana kwemicrosatellite (MSI). Panenge gumi neshanu muzana yekenza yakajeka inokonzerwa nenzira yeMSI.
PCR can be used to detect the length of microsatellite sites (microsatellites are tandem repeats of short DNA sequences in the genome of eukaryotes) in tumor cell DNA, and then compared with the corresponding normal cell DNA. With the popularization and application of NGS (Second Generation Sequencing), in addition to traditional immunohistochemistry and PCR detection, microsatellite status can also be detected on the NGS platform. To understand the authoritative NGS genetic testing institutions at home and abroad, please consult 400-626-9916.
Pamusoro pezvo, mamota emarara (anosanganisira ekuvhiya masampuli uye ekumisikidza) anogona zvakare kushandiswa pakuona kwemunohistochemical kwemajini mana asina kufanana, anosanganisira: MLH1, MSH2, MSH6, uye PMS2. Chero bedzi chero awa mapuroteni mana aripo, iro bundu ndere dMMR, chinova chikanganiso chekusafambiswa kwekugadzirisa basa. Kana ese mapuroteni mana achitaurwa zvakanaka uye bundu iri pMMR, iyo mismatch yekugadzirisa basa yapera.
Genetic kuyedza MSI mushumo ongororo
Mufananidzo unotevera unoratidza murwere anobva kuGlobal Oncologist Network akawanikwa aine MSI-H mushure mekuyedzwa kweMSI nekambani yekuongorora majini epamba (400-626-9916). Uyu murwere ane rombo rakanaka uye akakodzera immunotherapy.
Mumwe murwere paGlobal Oncologist Network akaedzwa zvakanaka neUS Keruis Gene (400-626-9916), uye mapuroteni ese mana aive akanaka (akanaka), zvinoreva kuti murwere aive pMMR, uye anga asingakodzere Immunotherapy yakatenderwa pamusoro apa. .
Dudziro yemhedzisiro yemabvunzo ekupedzisira inogona kuganhurwa muMSS (microsatellite solid), MSI-L (microsatellite yakadzika kusagadzikana) uye MSI-H (microsatellite yakadzika kusagadzikana). Kazhinji, dMMR yakaenzana neMSI-H, uye pMMR yakaenzana neMSS uye MSI-L.
Chenjedzo yekushandisa PD-1 inhibitors
- Iyi mishonga inopihwa seinopinda (IV) infusions vhiki mbiri kana nhatu dzese.
- Zvimwe zvinokonzeresa zvemishonga iyi zvinosanganisira kuneta, kukosora, kusvotwa, kurumwa, kuputika, kurasikirwa nechido, kuzvimbirwa, kurwadziwa pamwe chete uye manyoka.
- Zvimwe zvakakomba mhedzisiro zvinowanzoitika zvishoma nezvishoma. Dzimwe nguva, immune system inogona kurwisa zvimwe zvikamu, zvichikonzeresa zvakakomba kana kutyisidzira hupenyu mumapapu, ura, chiropa, gland inogadzira mahormone, itsvo, kana dzimwe nhengo.
- Munguva yekumisikidzwa, mamiriro emuviri wemurwere anoda kuongororwa munguva chaiyo.
Ipilimumab mishonga yekudzivirira
- Mushonga uyu unoshandiswa nivolumab (Opdivo) kurapa kenza yakajeka, asi haigone kushandiswa wega. Inofambiswa neiyo intravenous (IV) infusion, kazhinji vhiki dzese nhatu kwemana kutenderera kwekurapa.
- Iwo akajairika mhedzisiro mhedzisiro yemushonga iyi anosanganisira kuneta, manyoka, mapundu uye kuvaviwa.
- Paunenge uchishandisa ichi chinwiwa, zvakakomba mhedzisiro mhedzisiro inoita kunge yakajairika pane kushandisa PD-1 inhibitors. Kunge PD-1 inhibitors, uyu mushonga unogona kukonzera immune system kurwisa zvimwe zvikamu zvemuviri, izvo zvinogona kukonzera matambudziko akakomba nematumbu, chiropa, gland inogadzira mahormone, tsinga, ganda, maziso, kana dzimwe nhengo. Mune vamwe vanhu, izvi mhedzisiro zvinogona kutyisidzira hupenyu.
- Munguva yekumisikidzwa, mamiriro emuviri wemurwere anoda kuongororwa munguva chaiyo.
Nzira yekusarudza sei immunotherapy zvinodhaka mukenza yakajeka?
Chiremba wezvegomarara weAmerica Dr. Chiorean akati, "Pembrolizumab kana nivolumab inonyanya kufarirwa kuvarwere vane MSI-H. Nivolumab inosanganiswa ne ipilimumab (CTLA-4 inhibitor) haiwanzoshandiswa. Ini ndinofunga mutsauko i
s very small. Similarly, some people may argue that CTLA-4 may be better tolerated by the inhibitory response, but I also feel that the toxicity is significantly higher. ”
Dr. Messersmith said that when he needed to quickly obtain therapeutic effects, he used nivolumab and ipilimumab combination therapy. Adding ipilimumab can get an additional 15%–20% response rate. If the patient is symptomatic, it can be added. Even though this may increase adverse reactions, the treatment effect is even greater. This requires an assessment of the patient’s physical condition.
If patients and their families have difficulty in choosing an immunotherapy drug, they can seek domestic authoritative colorectal cancer experts for consultation through the Global Oncologist Network (+91 96 1588 1588) to determine the final, more suitable treatment plan.
