Metronomics Workshop meeting report published in May 15, 2013 issue of Cancer Research!
While the introduction of chemotherapy and radiation in the 1950s resulted in significant advances in our treatment of hematologic, testicular, and certain childhood cancers, the same cannot be said for most advanced solid tumors of the adult. According to recent NCI statistics, survival in these cases has remained flat for the past 50+ years, despite vast improvements in knowledge and technology. Underlying this observation is believed to be the refractoriness that comes with the greater intra-tumor heterogeneity seen in the advanced adult tumors. Recognition of tumor heterogeneity has led us to new understandings regarding the acquisition of tumor resistance, and more generally to a ‘systems biologic’ appreciation of the disease, involving host mechanisms that modulate tumor development. Meanwhile, some have suggested the control of tumor heterogeneity might come not with a new therapy, but with a new way to deliver classic therapy — that is, as ‘metronomic chemotherapy.’ At the time the term was introduced in an editorial to the original article introducing the concept, it related to a low-dose continuous chemotherapeutic backbone. Meanwhile, despite promising initial data, more general acceptance of the metronomic chemotherapy concept by clinicians has been hindered by inconsistencies in its definition, by the lack of understanding about its mechanism of action, and by the lack of tools to evaluate outcomes. The evaluation is complicated by the multiplicity of targets that have been identified to date. Frequent, continuous, low doses of chemotherapy have been shown to have effect on angiogenesis and stromal activation, as well as on immune, inflammatory and stem cell recruitment, three major host modulators of tumor growth.
This workshop addressed the problem of evaluating the metronomics concept from a quantitative, ‘systems’ perspective. We focused on tumor context — how do cell-cell interactions modify cancer dynamics, and how we might render our responses in quantitative terms that are testable, and most importantly, predictive. More specifically, the workshop aimed to address the problem of chemotherapeutic dose and frequency from a control-theoretic standpoint, focusing on each individual response target in turn: 1) angiogenesis, 2) stem cell response, and 3) immune response.
This workshop was part of the Center of Cancer Systems Biology's (CCSB) outreach and education effort funded by the National Cancer Institute's Integrative Cancer Biology Program (ICBP). The CCSB, based in Boston, Massachusetts, brings together diverse researchers to better understand the molecular and tissue-level events underlying the evolution and progression of cancer. The team of lab investigators and research staff assembled at the CCSB is working to develop novel quantitative and qualitative approaches to the problem of cancer, both at the molecular and at the systems levels.
Workshop Coordinator: Clare Lamont
Organizing Committee: Cassedra Enayo, Dr. Heiko Enderling, Dr. Shiva Kalinga, Melissa Klumpar, Winifred Nwangwu