title: Tumor heterogeneity and personalized cancer medicine: are we being outnumbered?
abstract: Tumor heterogeneity is regarded as a major obstacle to successful personalized cancer medicine. The lack of reliable response assays reflective of in vivo tumor heterogeneity and associated resistance mechanisms hampers identification of reliable biomarkers. By contrast, oncogene addiction and paracrine signaling enable systemic responses despite tumor heterogeneity. This strengthens researchers in their efforts towards personalized cancer medicine. Given the fact that tumor heterogeneity is an integral part of cancer evolution, diagnostic tools need to be developed in order to better understand the dynamics within a tumor. Ultra-deep sequencing may reveal future resistant clones within a (liquid) tumor biopsy. On-treatment biopsies may provide insight into intrinsic or acquired drug resistance. Subsequently, upfront combinatorial treatment or sequential therapy strategies may forestall drug resistance and improve patient outcome. Finally, innovative response assays, such as organoid cultures or patient-derived tumor xenografts, provide an extra dimension to correlate molecular profiles with drug efficacy and control cancer growth.
authors.affiliation: Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Geert A
authors.initials: GA
authors.lastname: Cirkel
authors.forename: Christa G
authors.initials: CG
authors.lastname: Gadellaa-van Hooijdonk
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Koudijs
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Willems
authors.forename: Emile E
authors.initials: EE
authors.lastname: Voest
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D057285:Precision Medicine
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor