Abstract IA11: Functional and clinical relevance of intratumor heterogeneity in breast cancer

Intratumor heterogeneity is a major obstacle toward understanding and treatment of cancers. We have analyzed cellular genetic and phenotypic heterogeneity in breast tumors using immune-FISH and found that higher pre-treatment genetic diversity predicts therapy resistance and distant metastases are the most diverse. In HER2+ tumors we detected startling heterogeneity for HER2 copy number gain and PIK3CA mutation using STAR-FISH, a novel method we developed, and determined that changes in the topologic distribution of cellular heterogeneity for these genetic alterations during neoadjuvant chemotherapy predicts long-term clinical outcome.We have also developed experimental models of subclonal heterogeneity and shown that polyclonal tumors grow faster and are more metastatic than monoclonal ones, a tumor-driver clone can be a minor subpopulation acting via non-cell-autonomous mechanisms, a dominant clone can outcompete the tumor-driver minor clone leading to tumor collapse, and that cancer therapies intensify clonal competition potentially leading to inadvertent acceleration of disease progression.Our results emphasize the need to study tumors as a whole and to understand the properties of cancer cell populations that compose tumors and interactions among them to be able to predict tumor evolution during disease progression and cancer therapies.Citation Format: Kornelia Polyak. Functional and clinical relevance of intratumor heterogeneity in breast cancer. [abstract]. In: Proceed...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Heterogeneity (Intratumor and Intertumoral): Oral Presentations - Invited Abstracts Source Type: research