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Improved understanding of the cellular and molecular makeup of tumors in the last 30 years has unraveled a previously unexpected level of heterogeneity among tumor cells as well as within the tumor microenvironment. The concept of tumor heterogeneity underlines the realization that different tumors can display significant differences in their genomic content as well as in their overall behavior. Our capacity to better understand the heterogeneous make up of tumors has very important consequences on our ability to design efficient therapeutic strategies to improve patient survival. This book highlights several aspects of tumor heterogeneity in the context of metastatic development and summarize some of the challenges posed by heterogeneity for tumor diagnostics and therapeutic management of tumors.

clear cell renal cell carcinoma --- tumor evolution --- tumor ecology --- intratumor heterogeneity --- multisite tumor sampling --- targeted therapy --- uterine carcinosarcoma --- endometrial carcinoma --- metaplastic carcinoma --- epithelial-to-mesenchymal transition --- clonality --- mutation --- TP53 --- PI3K/AKT pathway --- gene expression --- miRNA expression --- tumor microenvironment --- interstitial pH --- acidosis --- tumor heterogeneity --- magnetic resonance imaging --- hyperpolarized 13C MRI --- carbonic anhydrase --- lactic acid --- positron emission tomography --- esophageal squamous cell carcinoma --- precision medicine --- natural killer cells --- tumor mutation burden --- immunotherapy --- PET --- heterogeneity --- radiomics --- radiopharmaceuticals --- SUV --- nuclear medicine --- colon cancer --- Wnt signaling --- phenotypic plasticity --- EMT --- hybrid E/M --- collective and single-cell migration --- beta-catenin paradox --- breast cancer --- immune microenvironment --- DCIS --- ADH --- mammary gland --- cell fate --- 3D cultures --- organoids --- signaling --- single-cell RNAseq --- tumor endothelial cell --- metastasis --- angiocrine factor --- microsatellite instability --- colorectal cancer --- immune checkpoints --- deficient mismatch repair --- plasticity --- biomechanics --- circulating tumor cells (CTCs) --- extracellular vesicles --- metastatic niche --- epigenetics --- CTC-clusters --- single-cell analysis --- cellular heterogeneity --- circulating tumor cells --- pancreatic cancer --- epithelial mesenchymal plasticity --- target discovery --- review --- genomics --- intra-tumour heterogeneity --- subclonal diversity --- treatment resistance