DOI: https://doi.org/10.36347/sajb.2025.v13i06.011

Pages: 738-750

Cancer genomics has advanced a lot; a main problem is still turning molecular findings into treatments due to the variety of cells in each tumor and gaps in knowing certain pathway functions. Predicting whether a treatment will be effective is difficult right now which means that patient outcomes are often less than ideal. This research tackled the issue by studying whether looking at many genes and oncogenic pathways at the same time helps identify which patients may show cancer progression or treatment resistance. For this study, we looked at the genes, proteins and other molecules from a total of 1,500 patients in six major types of cancer (breast, colorectal, lung, melanoma, ovarian and prostate). We used genomic variant calling, analysis of gene pathways and detailed study of proteins with advanced bioinformatics and machine learning tools. The study found that TP53 mutations (OR: 2.14, 95% CI: 1.72-2.66, p < 0.001) and the PI3K/AKT/mTOR pathway being activated (OR: 1.89, 95% CI: 1.51-2.37, p = 0.003) were strongly linked to cancer not responding to treatment and negative outcomes. Tumors with a high number of mutations (≥ 10/Mb) reacted much better to immunotherapy (OR: 3.02, p < 0.001). Three subgroups of tumors were found through unsupervised analysis and these showed different chances of success: tumors with many mutations and high immune activity performed best (39.1% complete response), but those with mutations in PI3K and TP53 had the worst prognosis (28.5% progressive disease). Patients whose tumors were active in the PI3K/AKT pathway had progression-free survival of 8.2 months, significantly less (log-rank p < 0.001) than those whose tumors were not active. Evidence shows that integrative molecular profiling is better at predicting outcomes than the traditional method of classifying tumors by looking at slides. Study results show which molecular subgroups are most important to oncology and help link their treatment response to which therapy is best,