Single-Cell Omics: Strategies Towards Theranostic Biomarker Discovery Along the Continuum of Premalignant to Invasive Disease in Oncology

Abstract Omics-based single-cell and theranostics technologies will allow us to better understand tumor complexity, heterogeneity and resistance mechanisms, early detection, improved profiling and monitoring of cancer stem cells (CSCs), tumor cell heterogeneity, and targeted anticancer therapy to perform an exact prediction of disease susceptibility and diagnosis, as well as to develop a personalized early therapeutic strategy. Preclinical models mimicking human molecular profiles will offer the opportunity to study and characterize key shared molecular events such as angiogenesis, tumor microenvironment, and signaling cascades. The in vivo models will further lead to the generation and evaluation of specifically targeted oligonucleotide theranostic constructs that present high therapeutic potential. Therefore, comprehensive identification and characterization of precancerous cells and their progeny in all types of carcinomas at the single-cell level will allow the development and clinical application of theranostics. The evolution of tumorigenesis begins from a single-cell, which then progresses to heterogeneous cell populations with individually distinct molecular diversities. Genomic diversity and molecular heterogeneity of tumorigenesis complicate the discovery of theranostic, prognostic, and predictive biomarkers, and their translation into personalized/precision medicine for targeted early treatment. Systems biology analyses conducted on high-throughput data obtained from gene expression and other omics studies involving genomics, transcriptomics, proteomics, metabolomics, epigenomics, and glycomics have been successfully applied in oncology and cancer research. Therefore omics-based biomarker discovery at the single-cell level has critical importance in understanding early-stage oncogenic progress and tumor heterogeneity, and developing personalized onco-theranostic biomarkers, prophylactic/preventive therapies targeting specifically precancerous cell populations in various organs. This work provides a review on premalignant to invasive disease and single-cell, as well as omics-based, personalized onco-theranostics strategies in the context of precision medicine.