Abstract
The concept of personalized medicine is predominantly been pursued through genomic and transcriptomic technologies, leading to the identification of multiple mutations in a large variety of cancers. However, it has proven challenging to distinguish driver and passenger mutations and to deal with tumor heterogeneity and resistant clonal populations. More generally, these heterogeneous mutation patterns do not in themselves predict the tumor phenotype. Analysis of the expressed proteins in a tumor and their modification states reveals if and how these mutations are translated to the functional level. It is already known that proteomic changes including posttranslational modifications are crucial drivers of oncogenesis, but proteomics technology has only recently become comparable in depth and accuracy to RNAseq. These advances also allow the rapid and highly sensitive analysis of formalin‐fixed and paraffin‐embedded biobank tissues, on both the proteome and phosphoproteome levels. In this perspective, pioneering mass spectrometry‐based proteomic studies are highlighted that pave the way toward clinical implementation. It is argued that proteomics and phosphoproteomics could provide the missing link to make omics analysis actionable in the clinic.
Highlights
The concept of personalized medicine is predominantly been pursued through clinical outcome for most cancer types originates from a diverse array of factors, genomic and transcriptomic technologies, leading to the identification of including late diagnosis, tumor heteromultiple mutations in a large variety of cancers
It is already known that proteomic changes including posttranslational modifications are crucial drivers of oncogenesis, but proteomics technology has only recently become comparable in depth and accuracy to RNAseq
The Cancer Genome Atlas (TCGA)[4] and the International Cancer Genome Consoranalysis of formalin-fixed and paraffin-embedded biobank tissues, on both the tium (ICGC)[5] have surpassed the 1000 proteome and phosphoproteome levels. In this perspective, pioneering mass spectrometry-based proteomic studies are highlighted that pave the way toward clinical implementation
Summary
The genomic interrogation of diverse tumor types has led to the discovery of the genetic basis of their underlying abnormalities. Patients often do not respond to such targeted genetic therapies.[45,46] In many cases, poor or no responses can be traced back to heterogeneity of the tumors This subclonal architecture can arise through intercellular genetic instability, followed by selective outgrowth of clones that have a phenotypic advantage during treatment and within the given microenvironmental context.[47] Deep sequencing from single cells is a promising technology to decipher the complexity of tumors.[48] the resulting complex and heterogeneous mutation spectrum usually presents even greater challenges in selecting a treatment because it is difficult to predict whether the presence of genetic abnormalities will translate into downstream levels of gene expression and into the phenotype of cells and tissues. These immense archives of material present an invaluable resource for studying the underlying molecular mechanisms of cancer, testing known biomarkers and uncovering new ones
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