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Invited Commentary
April 27, 2020

Tumor Heterogeneity: Ignorance Is Not Bliss

Author Affiliations
  • 1Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
  • 3Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge
JAMA Netw Open. 2020;3(4):e203677. doi:10.1001/jamanetworkopen.2020.3677

Tumor heterogeneity encompasses interpatient heterogeneity, intrapatient heterogeneity among disease sites within a patient, and intratumoral heterogeneity within a single disease site. While tumor profiling provides a glimpse of interpatient heterogeneity, oncologists lack adequate tools in our diagnostic tool kit to fully characterize intrapatient and intratumoral heterogeneity, which remain critical barriers to developing targeted anticancer therapies, particularly in gastroesophageal adenocarcinoma (GEA).1-3 Although distal gastric cancer, historically associated with Helicobacter pylori, is becoming less common, proximal cancers arising near the gastroesophageal junction are becoming more common in Western countries owing to their associations with obesity and the Western diet.4 These cancers have extensive chromosomal instability leading to copy number alterations, including amplifications of genes encoding potentially actionable receptor tyrosine kinases, such as ERBB2 (OMIM 164870), EGFR (OMIM 131550), MET (OMIM 164860), and FGFR2 (OMIM 176943).

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