OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine.
Andrés López-CortésCésar Paz-Y-MiñoSantiago GuerreroAlejandro Cabrera-AndradeStephen J BarigyeCristian R MunteanuHumberto González-DíazAlejandro PazosYunierkis Perez CastilloEduardo TejeraPublished in: Scientific reports (2020)
Breast cancer (BC) is the leading cause of cancer-related death among women and the most commonly diagnosed cancer worldwide. Although in recent years large-scale efforts have focused on identifying new therapeutic targets, a better understanding of BC molecular processes is required. Here we focused on elucidating the molecular hallmarks of BC heterogeneity and the oncogenic mutations involved in precision medicine that remains poorly defined. To fill this gap, we established an OncoOmics strategy that consists of analyzing genomic alterations, signaling pathways, protein-protein interactome network, protein expression, dependency maps in cell lines and patient-derived xenografts in 230 previously prioritized genes to reveal essential genes in breast cancer. As results, the OncoOmics BC essential genes were rationally filtered to 140. mRNA up-regulation was the most prevalent genomic alteration. The most altered signaling pathways were associated with basal-like and Her2-enriched molecular subtypes. RAC1, AKT1, CCND1, PIK3CA, ERBB2, CDH1, MAPK14, TP53, MAPK1, SRC, RAC3, BCL2, CTNNB1, EGFR, CDK2, GRB2, MED1 and GATA3 were essential genes in at least three OncoOmics approaches. Drugs with the highest amount of clinical trials in phases 3 and 4 were paclitaxel, docetaxel, trastuzumab, tamoxifen and doxorubicin. Lastly, we collected ~3,500 somatic and germline oncogenic variants associated with 50 essential genes, which in turn had therapeutic connectivity with 73 drugs. In conclusion, the OncoOmics strategy reveals essential genes capable of accelerating the development of targeted therapies for precision oncology.
Keyphrases
- genome wide
- signaling pathway
- bioinformatics analysis
- copy number
- genome wide identification
- clinical trial
- transcription factor
- dna methylation
- protein protein
- squamous cell carcinoma
- epidermal growth factor receptor
- randomized controlled trial
- single cell
- computed tomography
- pregnant women
- young adults
- magnetic resonance
- cell proliferation
- magnetic resonance imaging
- cell cycle
- polycystic ovary syndrome
- epithelial mesenchymal transition
- dna damage
- single molecule
- binding protein
- papillary thyroid
- rectal cancer
- locally advanced
- insulin resistance
- open label
- image quality
- multiple sclerosis
- drug induced
- network analysis