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Updates found with 'certain proteins'

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Updates found with 'certain proteins'

IMMUNOTHERAPY IN LUNG CANCER- THE FUTURE OF CANCER CARE.Any cancer and lung cancer in particular creates a highly immunosuppressive environment locally i.e. our bodies immune cells are unable to recognize cancer cells.This is made possible by expression of certain proteins on surface of cancer cells which in turn binds to checkpoints like CTLA-4 and PD-1 present on surface of T-cells . This binding triggers a negative signal and stops T-cells from killing cancer cells. Immunotherapy drugs blocks the CTLA-4 and PD-1 which are checkpoints on T-cells , alternatively other drugs bind to the ligands present on surface of tumor cells. This leads to reactivation of the bodies ability to kill these cancer cells.Pembrolizumab is a immunotherapy drug that is a PD-1 inhibitor and it is approved in both 1st and 2nd line metastatic non small cell lung cancer.There is a IHC test that has to be done with a approved antibody for detecting the expression of PD-L1 ligand in tumor tissue.In the 1st line pembrolizumab is used in patients when PD-L1 expression is more then 50%.In the 2nd line the drug is used when expression >1%.The drug recently got its approval in 1st line in combination with chemotherapy based on the results of one of KEYNOTE trial. Nivolumab is approved in 2nd line irrespective of the PD-L1 expression for metastatic NSCLC.Immunotherapy drugs leads to long term stabilization of metastatic disease in approximately 20% of patients. Cost is a major limitation which restricts its use in developing country
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Maintenance with PARP inhibitor is the way forward in ovarian cancer:Median PFS in platinum sensitive relapse carcinoma ovary is approximately 10 months.20% of high grade serous carcinoma ovary have somatic or germline mutation in BRCA gene.Single stranded DNA breaks are repaired Base excision repair pathways of which PARP ( poly ADP ribose polymerase) enzymes are one of the key members.In presence of PARP inhibitors these single stranded breaks are converted into double stranded breaks and the repair of these double stranded breaks require intact Homologous recombination repair pathway. BRCA proteins are integral part of these Homologous recombination pathway.In presence of BRCA gene muatation the double stranded breaks produced in presence of PARP inhibitor bring about lethal damage to the cancer cells.Olaparib is the most extensively studied PARP inhibitor and it is approved in BRCA mutation positive relapse high grade carcinoma ovary as single agent after 3 or more lines of chemotherapy. Also Olaparib has been approved as maintenance in both BRCA mutated and wild type patients in relapse platinum sensitive high grade carcinoma ovary who attain CR or PR to last line platinum doublet.The reported PFS in this setting is around 18 months in BRCA mutated (SOLO-2 trial-using tablet olaparib 300mg twice daily) v/s 9 months in BRCA wild type based on STUDY- 19 Trial (Capsule Olaparib 400mg twice daily).It is important to note that about 15% patients remain progression free at 5 years in study-19 trial on Olaparib ( these long term progression free survival benefited both BRCA wild type and BRCA mutated subgroup) .Niraparib based on the result of NOVA trial (300 mg once daily) got approval in maintenance for both BRCA mutated and wild type patients in relapse platinum sensitive high grade carcinoma ovary who attain CR or PR to last line platinum doublet. Rucaparib at a dose of 600mg twice daily awaits its approval in similar setting with the promising results of the ARIEL3 presented in ESMO 2017.Main toxicity of Olaparib is anemia, nausea and fatigue. (Discontinuation rate 6%)Main toxicity of Niraparib is nausea and haematological (Thrombocytopenia> Anemia>Neutropenia) (Discontinuation rate 15%)Main toxicity of Rucaparib is anemia and elevation of liver enzyme (Discontinuation rate 13%)
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