Effect of cell proliferation pathway on accessibility to targeted therapeutics in the spectrum of co-occurring prognostic cellular pathways in pan-cancers.

Abstract

e15092 Background: Cellular pathways play a crucial role in prognosis and development of targeted therapies by impacting molecular mechanisms underlying disease progression. Targeted therapies can significantly reduce side effects while offering the potential to overcome challenges like drug resistance. This study aims to investigate prognostic cellular pathways that may be promising in guiding drug interactions pan-cancers. Methods: A cohort of 82 pan-cancer patients (Breast, Colorectal, Endometrium, Gall Bladder, Gastric, HNC, Lung, Melanoma, Ovary, Pancreas, Prostate, Urothelium) were retrospectively analyzed to understand the distribution of cellular pathways. Next Generation Sequencing (NGS) test was performed using OncoIndx Assay. Results: A total of 99 genomic alterations distributed across cellular pathways including proliferation, progression, dsDNA Repair, mismatch repair (MMR), tumor suppression and cell signaling were detected. Cell proliferation pathway alterations constituted the highest frequency with 43 mutations in 34.14% of patients while 31 alterations in tumor suppressor genes were identified in 34.14% patients. MMR and cell signaling pathways included a minor 2 and 1 alterations. Crucial pathways were also identified to co-occur with cell proliferation including tumor suppression (n = 13/28), cell progression (n = 2/28), dsDNA repair (n = 3/28), and MMR pathways (n = 2/28). From this group, 1 patient had recently undergone surgery showing no e/o recurrence or residual disease and the other patient was started with oral chemotherapy (capecitabine). Interestingly, both patients showed co-occurring tumor suppression pathway alterations. Conclusions: Cell proliferation pathway alterations, by presenting themselves as co-occurring with tumor suppression, cell progression, dsDNA repair and MMR pathway, open newer targets for multiple treatment lines.