Join the Drug Discovery Committee for this presentation on Vasculature and Oncology.

 

Kevin Foley, Ph.D., Director of In Vivo Pharmacology, Synta Pharmaceuticals

Title: Beyond Angiogenesis Inhibitors:  Developing a Next-Generation Antivascular Therapy for Cancer

Abstract: "Vascular disrupting agents (VDAs), sometimes referred to as vascular targeting agents, preferentially block blood flow in tumors relative to normal tissues, thereby inducing tumor hypoxia and necrosis. This is an intuitively attractive approach to the treatment of solid tumors, and is distinct from antiangiogenic therapies that inhibit new blood vessel growth and promote vascular normalization in tumors. However, first-generation VDAs have displayed poor single-agent efficacy in preclinical models due to the persistence of cancer cells at the well-perfused "viable rim" of tumors, which allows rapid tumor regrowth to occur.  We are developing a novel VDA, STA-9584, which has increased potency and an improved therapeutic index in preclinical models relative to other VDAs.  STA-9584 has a unique mechanism of action and blocks blood flow by specifically disrupting tumor microvasculature, not only in the center, but also at the periphery of tumors.  STA-9584 is currently being examined in a biomarker-intensive clinical trial in dogs with spontaneously occurring cancers."

 

Marsha Moses, Ph.D., Julia Dyckman Andrus Professor, Harvard Medical School and Director, Vascular Biology Program, Children's Hospital Boston

Title: "Molecular Regulation of Angiogenesis: From the Angiogenic Switch Through Tumor Progression: Implications for Therapy, Diagnosis and Prognosis" 

The Moses Lab has had a long-standing interest in identifying and characterizing the biochemical and molecular mechanisms underlying the regulation of angiogenesis during tumor progression, from the angiogenic switch through metastasis. Dr. Moses and her group have discovered a number of angiogenesis inhibitors, some of which are in pre-clinical development for use against a variety of cancers.

Significant efforts are also now underway in the Moses lab to identify the genes, and the proteins that they encode, that are responsible for the 'angiogenic switch'. This critical checkpoint, during which time a tiny benign, avascular tumor acquires the vascular phenotype, is a prerequisite for subsequent tumor growth and progression. The Moses Lab has recently identified and validated a number of genes which are differentially expressed during the angiogenic switch and is currently developing molecular and biochemical interventions to regulate the switch by targeting some of these genes.

To complement these studies, Dr. Moses has established a Proteomics Initiative in her laboratory that has now led to the discovery of a panel of urinary cancer biomarkers that not only predict disease status and stage in cancer patients but are also sensitive and specific markers of disease progression and therapeutic efficacy of cancer drugs. A number of these urine tests are currently in clinical testing as potential cancer diagnostics and prognostics. 

About Marsha A. Moses 

Marsha A. Moses received a PhD from Boston University and completed a National Institutes of Health postdoctoral fellowship at Children's Hospital Boston and MIT. She is the Julia Dyckman Andrus Professor at Harvard Medical School and the Director of the Vascular Biology Program at Children's Hospital Boston.  Dr. Moses was elected to the Institute of Medicine of the National Academies of the United States in 2008. She is the recipient of a number of NIH and foundation awards.  Dr. Moses also received Harvard Medical School's A. Clifford Barger Mentoring Award in 2003 and the Joseph B. Martin Dean's Award for the Advancement of Women in 2009.