Tissue-specific and time-dependent mechanisms of metastasis
Ponente: Roger Gomis
Institute for Research in Biomedicine (IRB) [Barcelona]
Host: Pedro A. Lazo-Zbikowski
Salón de actos del Centro de Investigación del Cáncer
Metastatic progression relies on specific biological steps that need to be targeted to improve current therapeutic strategies. Chemotherapy targets high-proliferating tumor cells rather than the low-proliferating metastastic tumor cells, which can then spread from the primary tumor to distant sites, where they resist conventional treatments, proliferate, and cause vital organ failure. Strikingly, different BCa types show distinct metastatic organ tropism, and acquisition of metastasis may vary from one tumor type to another. Our group and others have help to simplify metastasis into an orderly sequence of basic steps, which has helped to rationalize the complex set of biological properties required for metastatic disease. However, the steps of the kinetics and mechanisms that regulate tissue-specific metastasis remain poorly understood. Cancer cells must orchestrate diverse cellular functions to overcome the difficulties of transiting the metastatic cascade; these functions are limited to cell-autonomous and non-autonomous traits and are highly dependent on the interactions between the metastatic cell and the tumor and host stroma. Several functions can be required to implement a single step, or a single function may influence multiple steps. This speciation is reflected by the distinct kinetics of cancer relapse at different sites in the same patient, and by the coexistence of malignant cells that differ in organ tropism in patient-derived samples. As we understand more about the biology of BCa cells, we can begin to address how best to treat this form of disease. Key to determining whether dormant solitary cells or micrometastases represent valid targets is knowledge of the underlying biology of dormancy and the probability of cells progressing to active metastatic growth. This progression is poorly understood in preclinical models and even less so clinically and has become of our interest.