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C. Swanton
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PL02 - Will Personalised Therapies Ever “Cure” Metastatic NSCLC? (ID 73)
- Event: WCLC 2013
- Type: Plenary Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:D. Gandara, D. Carney
- Coordinates: 10/28/2013, 08:15 - 09:45, Plenary Hall, Ground Level
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PL02.3 - Tumour Heterogeneity as an Obstacle to Cure (ID 635)
09:00 - 09:20 | Author(s): C. Swanton
- Abstract
Abstract
Despite advances in cancer genomics, most advanced solid tumors remain incurable and drug resistance is almost inevitable. Two important lessons have emerged, which may provide an explanation for difficulties that have been encountered in improving cancer survival outcomes. First, each tumor contains an individual assortment of multiple genomic aberrations, few of which are shared between patients with the same histopathological tumor subtype. Second, evidence suggests that these anomalies appear to vary within individual tumors, both spatially and temporally during the disease course, indicating substantial intratumor heterogeneity. Branched evolutionary growth and intratumor heterogeneity results in coexisting cancer cell subclones with variegated genotypes and phenotypes that may be regionally separated within the same tumor and alter in dominance over time. Variegated phenotypes, resulting from intratumoral genetic heterogeneity and the emergence of new subclones at relapse, are likely to have important implications for developing novel targeted therapies and for preventing the emergence of drug resistance. Intratumor heterogeneity and sampling bias, resulting from single biopsy-driven biomarker discovery and validation approaches, may also contribute to the recently reported failures in implementation of robust biomarkers in the clinical setting. In this talk, the two fundamental principles of Darwinian Evolution, diversity and selection, will be discussed in relation to achieving better cancer survival outcomes.