Abstract
The increasing incidence combined with constant rates of early diagnosis and mortality of colorectal cancer (CRC) over the past decade worldwide, as well as minor overall survival improvements in the industrialized world, suggest the need to shift from conventional research and clinical practice to the innovative development of screening, predictive and therapeutic tools. Explosive integration of next-generation sequencing (NGS) systems into basic, translational and, more recently, basket trials is transforming biomedical and cancer research, aiming for substantial clinical implementation as well. Shifting from inter-patient tumor variability to the precise characterization of intra-tumor genetic, genomic and transcriptional heterogeneity (ITH) via multi-regional bulk tissue NGS and emerging single-cell transcriptomics, coupled with NGS of circulating cell-free DNA (cfDNA), unravels novel strategies for therapeutic response prediction and drug development. Remarkably, underway and future genomic/transcriptomic studies and trials exploring spatiotemporal clonal evolution represent most rational expectations to discover novel prognostic, predictive and therapeutic tools. This review describes latest advancements and future perspectives of integrated sequencing systems for genome and transcriptome exploration to overcome unmet research and clinical challenges towards Precision Oncology.
Highlights
colorectal cancer (CRC) classification, other independent prognostic markers include several mutated genes [47,48] and primary tumor site of origin in the left or right colon associated with distinct genetic characteristics [44], while microsatellite instability has been confirmed as predictor of survival for CRC but across multiple other cancer types as well [40]
Extensive inter- and intratumor heterogeneity was identified, matched primary tumor (PT) and metastatic tumor (MT) were highly concordant for driver mutations, suggesting the early acquisition of aggressive alterations responsible for metastasis, while the modeof tumor evolution and sub-clonality correlated with disease stage
For colorectal cancer, Strickler et al [19] reported that mutation frequencies identified by cell-free DNA (cfDNA)-targeted NGS (tNGS) matched those of tumor sequencing studies and that tNGS liquid biopsies were capable of detecting alterations driving therapeutic resistance, potentially as a response to treatment
Summary
The validity of next-generation sequencing (NGS) at both bulk and single-cell levels in the identification of disease associated variants and tumor heterogeneity has transformed biomedical and cancer research [1,2,3,4,5,6]. Conventional research on the basis of tumor homogeneity and stability, as well as the linear single-gene transcription concept, has improved oncological outcomes for colorectal cancer (CRC) patients through the standardization of diagnosis, TNM staging and multimodal treatment, major clinical challenges remain unresolved [13,14]. Evidence on extensive inter- and intra-patient genetic, genomic and transcriptional heterogeneity [7,8,9] has underlined the need for combinatorial targeted therapy to improve the rates of disease-free, progression-free and overall survival [17,20,21,22]. This review discusses latest science advances, bottlenecks and future capabilities of genomic and transcriptomic landscape dissection in time and space towards precise prediction of drug response and tailored treatment for sporadic colorectal cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
