Spatiotemporal diversification of intrapatient genomic clones and early drug development concepts realize the roadmap of precision cancer medicine.

The unmet clinical needs of high relapse and cancer-related death rates are reflected by the poor understanding of the genome-wide mutational landscape and molecular mechanisms orchestrating therapeutic resistance. Emerging potential solutions to this challenge include the exploration of cancer genome dynamic evolution in time and space. Breakthrough next-generation sequencing (NGS) applications including multiregional NGS for intratumor heterogeneity identification, repeated cell-free DNA/circulating tumor DNA-NGS for detecting circulating genomic subclones and their comparison to reveal intrapatient heterogeneity (IPH) could identify the dynamic emergence of resistant subclones in the neoadjuvant, adjuvant and metastatic setting. Based on genome-phenotype mapping[SB1] , and potential promising findings, rigorous evaluation of IPH spatiotemporal evolution and early drug development concepts in innovative clinical trials could dramatically speed up the translational process to achieve clinical precision oncology.

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