Dear Colleagues, 

Cancer cells evolve by acquiring novel genetic/non-genetic aberrations, partially due to their genetic instability, and by adapting to changing conditions. Such evolution of cancer cells is often overlaid with Darwinian evolution, and as cancer cells spread into a new circumstance (metastasis), the diversity of the cancer cells further increases. As a result, patients’ tumors possess a considerable amount of tumor heterogeneity at various levels, e.g., morphological, cellular, molecular, and/or metabolic levels. Such diversity in human cancers has long been recognized, however, recent rapid advents of next-generation sequencing (NGS) technologies have accelerated research for tumor heterogeneity and have transformed our understanding of the extent of genetic heterogeneity in various human cancers.

This Special Issue welcomes all aspects of tumor heterogeneity, intra-tumor heterogeneity and inter-lesion heterogeneity, in terms of genetic/non-genetic (molecular) levels, cellular and histological levels, tumor microenvironment levels including infiltrating immune cells, metabolic levels, and associations between these various levels of tumor heterogeneity (e.g., how molecular-level tumor heterogeneity affects infiltration of immune cells). This Special Issue especially welcomes manuscripts that report the roles of tumor heterogeneity in drug resistance. Due to the diversity of cancer cells, they do not uniformly respond to treatments; minor clones with inherent resistance or treatment inducible drug tolerant cells survive. Furthermore, heterogeneity in the acquired resistance mechanisms to the front-line therapy will reduce the efficacy of the next treatment.

With the clinical application of molecular targeted therapies and cancer immunotherapies, cancer treatment has become a precision medicine. The precise treatment means that a small change in cancer cells may affect the efficacy of the treatment. I expect that papers that will be published in this Special Issue will help us to further understand tumor heterogeneity and to propose novel treatment strategies to eradicate all the cancer cells beyond the tumor heterogeneity.

Dr. Kenichi Suda
Guest Editor

Manuscript Submission Information

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• intra-tumor heterogeneity (ITH)
• metastases
• molecular evolution
• molecular phylogenetics
• biomarkers
• inherent and acquired resistance
• nest generation sequencing (NGS)