Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy.

Chemotherapy has been used to inhibit cancer growth for decades, but emerging evidence shows it can affect the tumor stroma, unintentionally promoting cancer malignancy. After treatment of primary tumors, remaining drugs drain via lymphatics. Though all drugs interact with the lymphatics, we know little of their impact on them. Here, we show a previously unknown effect of platinums, a widely used class of chemotherapeutics, to directly induce systemic lymphangiogenesis and activation. These changes are dose-dependent, long-lasting, and occur in healthy and cancerous tissue in multiple mouse models of breast cancer. We found similar effects in human ovarian and breast cancer patients whose treatment regimens included platinums. Carboplatin treatment of healthy mice prior to mammary tumor inoculation increased cancer metastasis as compared to no pre-treatment. These platinum-induced phenomena could be blocked by VEGFR3 inhibition. These findings have implications for cancer patients receiving platinums and may support the inclusion of anti-VEGFR3 therapy into treatment regimens or differential design of treatment regimens to alter these potential effects.

Assessing drug response in engineered brain microenvironments.

Tissue engineered systems are important models for the testing and discovery of therapeutics against a number of diseases. The use of these models in vitro can expand both our understanding of the mechanisms behind disease and allow for higher throughput and personalized modeling of therapeutic response. Over the past decade there has been an explosion of models of neurological disorders that can be used in vitro to study new therapies against devastating neurodegenerative, neurodevelopmental, and neuro-oncological disease. These models span several types of engineered microenvironments which are produced using microfluidic devices, microtissue technology and/or the incorporation of biomaterial scaffolds to model neurological conditions such as; Alzheimer's disease, idiopathic autism, Parkinson's disease, Zika-induced microcephaly and neoplasms. Using engineered brain microenvironments, therapeutics can be tested in more physiologically relevant ways leading to new knowledge of the underlying causes and interactions occurring at the tissue level. However, much is still left to learn and model within these systems to make them truly valuable in the discovery and testing of novel therapies. Here we review the current state of the art of engineered brain microenvironments being used specifically to screen and test new therapeutic strategies and discuss the current benefits and limitations that still exist.