Background: The endoplasmic reticulum (ER) stress initiates unfolded protein response (UPR) to re-establish ER homeostasis as an adaptive pathway in cancer. However, persistent ER stress triggers the apoptotic pathway. The term "kidney cancer" (KC) actually refers to a number of distinct cancers, each of which has its own distinctive histology, genetic alterations, clinical course, and therapeutic response. Apart from the usual socio-economic factors generally implicated in the occurrence of cancer; kidney cancer is generally observed in a number of genetic diseases such as: Von hippel-lindau syndrome (VHL), Tuberous sclerosis complex (TSC), Birt hogg dube syndrome (BHD), Hereditary papillary renal cell carcinoma, Hereditary leiomyomatosis, Hereditary paranglioma and pheochromocytoma syndrome, Downden's syndrome. Historically, patients with renal tumors underwent the same surgical procedures, and received similar drug treatments, none of which worked, for the treatment of KC. The available systemic therapies did not increase survival for patients with advanced disease, although there would occasionally be a response. Despite significant improvements in cancer detection and treatment, one of the most difficult aspects of the field is still disease management especially for those living with genetic diseases.
Methods: The purpose of this research was to generate peptides from natural in sillico that might be used as kidney cancer therapeutics. Target prediction, protein-protein interaction, and protein-peptide molecular docking have all been used as calculation techniques.
Results: The network of critical KC gene consist of C3AR1, CSNK2A2, ACE, DPP4, CAPN1, FPR2, HLA-A and MMP2 together with predicted kinases such as RPS6KA5, MAPK14, CSNK2A1, PRKCD, CDK1 and HIPK2in addition to transcription factors such as IRF8, TCF3, ERG, CREB1, EZH2, SPI1, IRF1 and SUZ12. The identified molecular target of isolated peptides HLA class I histocompatibility antigen A-3, Lipoxin A4, Dipeptidyl peptidase IV, Angiotensinconverting enzyme, Cyclooxygenase-2, C3a anaphylatoxin chemotactic receptor, Melanocortin receptor 4, Neurotensin receptor 1, Mu opioid receptor, Delta opioid receptor and Calpain 1.
Conclusion: Overall, the results showed that GVSK, PGP, WQR, YGGF and IF peptides are promising candidates for further study. Future work would be needed to test the therapeutic properties of these hydrolysate peptides by in vitro and in vivo approaches.
Keywords: Genetic diseases, Kidney cancer, Peptide treatment, Molecular docking
