期刊
ADVANCES IN ANATOMIC PATHOLOGY
卷 22, 期 4, 页码 267-272出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/PAP.0000000000000078
关键词
landscape; pathology; ecology; personalized medicine; precision medicine
类别
资金
- NIH/NCI PS-OC [U54CA143970]
- Analytic Microscopy Core Facility at the H. Lee Moffitt Cancer Center & Research Institute, an NCI-designated Comprehensive Cancer Center [P30-CA076292]
A major goal of modern medicine is increasing patient specificity so that the right treatment is administered to the right patient at the right time with the right dose. While current cancer studies have largely focused on identification of genetic or epigenetic properties of tumor cells, emerging evidence has clearly demonstrated substantial genetic heterogeneity between tumors in the same patient and within subclones of a single tumor. Thus, molecular analysis from populations of cells (either a whole tumor or small biopsy of that tumor) is, at best, an incomplete representation of the underlying biology. These observations indicate a significant need to define intratumoral evolutionary dynamics that yield the observed spatial variations in cellular properties. It is generally accepted that genetic heterogeneity among cancer cells is a manifestation of intratumoral evolution, and this is typically viewed as a consequence of random mutations generated by genomic instability within the cancer cells. We suggest that this represents an incomplete view of Darwinian dynamics, which typically are governed by phenotypic variations in response to spatial and temporal heterogeneity in environmental selection forces. We propose that pathologic feature analysis can provide precise information regarding regional variations in environmental selection forces and phenotypic adaptations. These observations can be integrated using quantitative, spatially explicit methods developed in landscape ecology to interrogate heterogenous biological processes in tumors within individual patients. The ability to investigate tumor heterogeneity has been shown to inform physicians regarding critical aspects of cancer progression including invasion, metastasis, drug resistance, and disease relapse.
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